P-019 Ustekinumab IV 6 mg/kg Loading Dose Re-induction Improves Clinical and Endoscopic Response in Crohn’s Disease: A Case Series
Park Sunhee 1, Evans Elisabeth2, Sandborn William3, Boland Brigid4. 1UC Irvine, San Diego, California, 2Inflammatory Bowel Disease Center, Division of Gastroenterology, UC San Diego Health System, La Jolla, California, 3University of California, San Diego, La Jolla, California, 4UCSD, La Jolla, California
CASE: Ustekinumab, a monoclonal antibody to the p40 subunit shared by interleukins-12,23, is approved for treatment of patients with moderate to severe Crohn’s disease(CD) with a weight-based intravenous ustekinumab induction followed by subcutaneous maintenance therapy (Feagan et al, 2016). TNF inhibitors are associated with clinical and endoscopic response. Among anti-TNF experienced patients receiving induction at Week 6, higher serum drug concentrations are associated with clinical response, suggesting that there may be a therapeutic benefit to optimizing ustekinumab drug concentrations to augment clinical response (Sandborn et al, 2012). We present our preliminary experience at a tertiary care center to support this hypothesis.
We report 3 patients with moderate to severe anti-TNF experienced CD initiated on ustekinumab therapy, who had minimal response after non-weight based subcutaneous induction; loading with intravenous weight-based Ustekinumab led to clinical and/or endoscopic improvement (Table 1).
Patient 1 was a 35-year-old woman with ileocolonic CD with prior intestinal resections and colectomy with ileoanal pouch who had failed multiple anti-TNF therapies and vedolizumab. The patient had improvement in clinical and endoscopic measures after intravenous reloading with ustekinumab. Initiation of ustekinumab combination therapy as well as steroids did not improve disease activity; however, pouchoscopy three months after reloading dose showed improvement in endoscopic disease activity, and the patient was able to wean off corticosteroids.
Patient 2 was a 44-year-old man with history of Crohn’s ileocolitis with perianal fistulas with prior small bowel resections. The patient was a primary non-responder to Infliximab and did not respond to Vedolizumab combination therapy. He was initiated on ustekinumab combination therapy with improvement in ulceration at the ileocolonic anastomosis; however, he had ongoing abdominal pain, diarrhea, and perianal drainage. After intravenous induction with ustekinumab, his clinical symptoms improved and was able to taper off steroids.
Patient 3 was a 26-year-old man with history of ileocolonic Crohn’s disease who had secondary loss of response to Infliximab therapy, primary non-response to adalimumab, and was started on ustekinumab combination therapy. He was subsequently hospitalized with an intra-abdominal abscess requiring drainage and antibiotics. After intravenous reinduction of ustekinumab, he had clinical and endoscopic response and successfully tapered off steroids.
All 3 patients showed improvement in clinical response after intravenous dosing of ustekinumab with successful tapering of corticosteroids. Endoscopic evaluations showed endoscopic as well as histologic improvement. With further development of therapeutic drug monitoring for ustekinumab, drug concentrations may aid in the use of intravenous loading of ustekinumab, identifying appropriate patients where a rescue dose may augment a sub-optimal response. Based on these preliminary findings, re-induction dosing of ustekinumab in patients on maintenance therapy with sub-optimal clinical response or ongoing steroid dependence may improve outcomes. Prospective studies in patients with Crohn’s disease receiving ustekinumab therapy are warranted to elucidate the best approach for optimizing drug therapy.
P-020 Therapeutic Effect of Vancomycin in UC Patients Associated With PSC: Case Series
Lodhi Fahad, Mankongpaisarnrung Charoen, Gerber Daniel; Charabaty Aline. Georgetown University Hospital, Washington, District of Columbia
BACKGROUND: Up to 5% of patients with ulcerative colitis (UC) have primary sclerosing cholangitis (PSC). Small studies have shown a decrease in alkaline phosphatase (ALP) in PSC patients treated with vancomycin, suggesting its potential therapeutic role. In our practice, we observed clinical benefits of vancomycin in controlling UC disease activity in patients with UC with PSC, and in the absence of C. difficile infection.
METHODS: A retrospective chart review of those with active UC refractory to standard treatment with PSC was conducted at Georgetown University Hospital. Prior treatments, endoscopic findings, and blood work results were collected.
RESULTS: Six patients with active UC with PSC were treated with vancomycin 125 mg PO QID for 4-8 weeks to induce remission, followed by maintenance with vancomycin 125 mg PO TID. All were female with age between 17-52 and tested negative for C. difficile prior to initiation of vancomycin. Two patients had a remote history of C. difficile. Five had UC pancolitis; one had indeterminate colitis. Three patients were post-OLT with evidence of recurrent PSC (with two patients on tacrolimus and one on mycophenolate mofetil). UC duration ranged from 6-21 years.
All had documented active disease by colonoscopy (Mayo score 1-2) and/or inflammatory markers and were assessed at 4-6 weeks after vancomycin initiated: all achieved clinical remission and maintained remission at follow-up (0.5-2 years). Colonoscopy results at 1 year after initiation of vancomycin were available for 4 patients: Three patients had Mayo score of 0 and one patient had a Mayo score 1, with an average reduction of UC Mayo score on vancomycin of 1.67. Four patients had a decrease in ALP. All tolerated the drug well without reported side effects.
CONCLUSION(S): In our subset of patients with active UC/PSC, who have failed standard treatments (mesalamine, immunomodulators, biologics), vancomycin was effective and safe at inducing clinical, biochemical and endoscopic remission. Clinical remission with vancomycin occurred rapidly within 4-6 weeks of initiating treatment and was maintained for up to 2 years of follow-up. Liver enzymes improved on vancomycin. Prospective studies with a larger number of UC/PSC patients and a long-term follow-up are needed to better establish the therapeutic role of vancomycin in this subset of patients. Proposed mechanisms of action are the induction of regulatory T cells, increased TGF-B via TNF-alpha pathway, and/or shifting aberrant cytokine profiles through gram-negative bacteria composition.
P-021 Young Investigator Common Variable Immunodeficiency Masquerading as Ulcerative Colitis
Cooley David 1, Liggett Michael2, Gamarra Roberto1. 1Providence-Providence Park Hospital/Michigan State University of Human Medicine, Southfield, Michigan, 2Cincinnati State, Cincinnati, Ohio
V.R. is a 24 year old, African American female, with a history of Lupus, recurrent UTI's, sinus infections, ear infections, pneumonia and a family history of Crohn's disease, who was originally referred to gastroenterology clinic for microcytic anemia. Over the two months prior to her initial visit, she was having multiple episodes of bilious emesis daily. Additionally, she was experiencing diffuse abdominal cramping and was having 3-4 loose BM's per day with occasional bright red blood coating her stool. She reported that she had been known to have anemia for many years but without a definitive explanation. She did endorse heavy menses which had not previously been evaluated. Repeat blood work noted iron deficiency anemia and there were no findings consistent with sickle cell. As a result of her anemia, she was scheduled for an EGD and colonoscopy.
Her EGD was notable for monilial esophagitis as well as erythematous gastropathy and gastritis with biopsies reported as atypical lymphoid infiltrates. Her colonoscopy findings were notable for prominent lymphoid nodules in the ileum which were biopsied and found to be atypical lymphoid infiltrates. She had an inflamed appendiceal orifice consistent with a cecal patch which was biopsied and returned as atypical lymphoid infiltrates. Additionally, she had mild to moderate patchy proctosigmoiditis with biopsies again returning as atypical lymphoid infiltrates. The biopsies were reviewed by an expert pathologist who noted a paucity of plasma cells, confirmed with negative CD 138 immunostaining. Furthermore, staining for a malignant process such as lymphoma was found to be unlikely.
Given the constellation of findings, immunoglobulin electrophoresis to check for Common Variable Immunodeficiency (CVID) was done as was flow cytometry to rule out lymphoma. Clonality was not established on flow cytometry and serum immunoglobulin electrophoresis was consistent with CVID with her IgG being low at 72, her IgA low at less than 7 and her IgM low at 29.
She was referred to an immunologist who started her on immunoglobulin infusions. She has done well for nearly one year.
CVID is defined as reduced concentrations of IgG along with low levels of IgA and/or IgM, a poor or absent response to immunizations, and not having another diagnosis of an immunodeficiency state. The majority of patients are diagnosed between ages 20 and 45. In a nearly forty year study looking at nearly 500 patients with CVID, it was found that 15% of them had gastrointestinal inflammatory disease. Diarrhea is the most common symptom in patients who have gastrointestinal disease and the most common presentation is one that resembles IBD, either ulcerative colitis or Crohn's disease. One theory regarding the IBD like inflammation in CVID patients may be related to abnormal cytokine production through a T-cell related pathway, however, given the variability of the presentation, there are likely multiple mechanisms involved.
This case is significant for the practicing gastroenterologist. The patient's endoscopic presentation, clinical symptoms and lab findings were consistent with a diagnosis of ulcerative colitis. One must keep a broad differential in mind as it impacts treatment and surveillance.
P-022 Young Investigator Novel Therapy for Collagenous Colitis - A Case Report
Sharp Melissa 1, White Betty2. 1Loma Linda University, Tacoma, Washington, 2Digestive Health Specialists, Tacoma, Washington
Microscopic colitis is a chronic, inflammatory disease of the colon that is characterized by chronic, non-bloody, watery diarrhea, insidious or acute onset. It typically occurs in middle-aged female patients. On endoscopy, the colon is typically normal in appearance, with changes of abnormal collagen layers and intraepithelial lymphocytes identified on biopsies. There are two subtypes of Microscopic colitis, lymphocytic and collagenous colitis. The underlying pathophysiology is poorly understood. There may be a mucosal immune response in genetically predisposed patients. Research has been able to identify triggers amongst some patients who use nonsteroidal anti-inflammatory drugs, various prescription drug therapies, smoking and Clostridium difficile and Yersinia infections. Microscopic colitis can be associated with several other autoimmune conditions. Numerous treatment studies for Microscopic Colitis have included use of Budesonide, Mesalamine, Bismuth salicylate, Prednisolone/Prednisone, Cholestyramine + Mesalamine, Boswellia serrata and probiotics.
Vedolizumab is a humanized monoclonal antibody that specifically binds to the α4β7 integrin and blocks the interaction of α4β7 integrin with mucosal addressin cell adhesion molecule-1 and inhibits the migration of memory T-lymphocytes across the endothelium into inflamed gastrointestinal parenchymal tissue. Vedolizumab is approved for adults with moderate to severe Ulcerative Colitis and Crohn’s Disease, who have had an inadequate response with, lost response to, or were intolerant to a tumor necrosis factor (TNF) blocker, immunomodulator or corticosteroids; or became corticosteroid dependent.
This patient is a 70-year-old female with a history of refractory Collagenous Colitis, Arthritis, Dermatitis Herpetiformis, COPD, Osteoporosis and Sleep Apnea. She was originally diagnosed with Collagenous Colitis on Colonoscopy 2/16/2012. Initial steroid therapy led to personality changes. Lialda and Colestid therapies were tried and found to be ineffective as single agents. Very minimal benefit experienced with use of Loperamide therapy. High dose Budesonide again led to personality changes; she has tolerated lower doses. Given her history of steroid therapies for her COPD and high dose Budesonide for her Collagenous Colitis, she was diagnosed with Adrenal Insufficiency. An EGD in 2012 was negative for Celiac Disease. Stools have been negative for Clostridium difficile.
In May of 2016, our patient began use of Vedolizumab. She experienced an initial response with decreased stooling. She was previously experiencing >10 stools daily, which diminished to 2-3 stools daily. A repeat Colonoscopy 2/10/16 again confirmed the presence of Collagenous Colitis on biopsy. On 5/12/16, she met with a Dietician to further explore dietary changes that could enhance her disease control. Some changes were found to be of benefit, however, this did not result in a significant change. Overall, her quality of life has been improved on Vedolizumab and continued use of bile sequestering therapy, Mesalamine, anti-diarrheal therapy and one Budesonide 3mg. Although Vedolizumab it is not currently FDA approved for the use of Collagenous Colitis, it is a novel therapy for the treatment of this condition.
P-023 Vedolizumab for the Treatment of Refractory Microscopic Colitis
Samuel Gbeminiyi 1, LeStrange Aimee2, Charabaty Aline2. 1Howard University Hospital, Washington, District of Columbia, 2Georgetown University Hospital, Washington, District of Columbia
BACKGROUND: Microscopic colitis (MC) is a common cause of chronic watery diarrhea. It is more prevalent in women and typically manifests in the 6th-7th decade of life. The colon mucosa typically appears normal on endoscopy and biopsies reveal an increase in intraepithelial lymphocytes/IEL (lymphocytic colitis) sometimes associated with a thick subepithelial collagenous membrane (collagenous colitis). Guidelines position budesonide as the first-line treatment for MC, however, relapse rate is high when budesonide is stopped. A subset of MC patients may be refractory or intolerant to budesonide, hence requiring a different treatment approach. We here present a case of severe and refractory MC that responded to vedolizumab, an α4β7 integrin monoclonal antibody.
RESULTS: Case presentation: The patient is an 84 -year old female, previous smoker, who presented to the GI clinic for chronic diarrhea. She was diagnosed with MC at age 65 and was treated with budesonide with partial improvement of her diarrhea. However, for the last 2 years, she stopped responding to budesonide and started experiencing steroids side effects. She complained of explosive diarrhea up to 8-10 times a day, with fecal urgency and incontinence. She was otherwise healthy, and the diarrhea and incontinence greatly affected her quality of life. Stool studies were negative, celiac and thyroid work-up were negative, and she denied NSAIDs, PPI and SSRI use. Colonoscopy with exam of the terminal ileum and random biopsies of normal colon mucosa confirmed MC, collagenous type. She failed treatment with mesalamine, fiber supplements, cholestyramine, anti-diarrheal and eluxadoline. Vedolizumab was started and the patient achieved clinical remission as early as after the 1st induction dose. She had 1-2 formed BM/day for the first time in years, and her fecal urgency and incontinence resolved. She completed 3 induction doses of vedolizumab with plan to reassess her long-term response and decide if maintenance therapy is needed.
Discussion: The treatment of MC consists of controlling the diarrhea and improving the patient’s quality of life while minimizing potential side effects of the treatment drug. It is important to find effective and safe alternative to budesonide, in patients who become steroids dependent, refractory or intolerant. Immunomodulators and anti-tumor necrosis factor have been described as options for the treatment of refractory MC, however, they carry an increased risk of serious side effects in the elderly population. Vedolizumab is a α4β7 integrin monoclonal antibody that blocks the trafficking of inflammatory T cells to the gut. This mechanism of action should halt the increased IEL seen in MC, and the gut-selective action of vedolizumab makes it an attractive safe treatment option for patients with MC.
CONCLUSION(S): Studies need to be done to clarify the role of vedolizumab in treating refractory MC and to determine the duration of treatment that is needed to achieve and maintain remission of MC.
P-024 Four Cases of Reoperative Pouch Surgery After Failed Minimally Invasive Pouch Creation
Aydinli H. Hande 1, Schwartzberg David1, Remzi Feza2. 1NYU Langone Medical Center, New York, New York, 2NYU School of Medicine, New York, New York
Ulcerative colitis (UC) treatment has evolved from an unknown disease process without effective diagnostic or therapeutic tools, to currently a vast field with biologic agents and creation of ileal-pouch-anal anastomosis to restore continence. Total proctocolectomy with J-pouch has become the standard of care for patients with UC and familial adenomatous polyposis. With a movement towards minimally invasive techniques, such as laparoscopy and robotic assisted operations, there has been an emergence of complications that were relatively rare in open J-pouch creation. We share 4 cases of reoperative pouch surgery where the mechanical complications after initial minimally invasive pouch creation led to pouch failure. Mean age was 29 (16-38) years old and mean body mass index was 22.9 kg/m2 (17-24). All patients were female and underwent 3-stage laparoscopic pouch creation for medical treatment resistant ulcerative colitis. Mean time from J-pouch creation to presentation for redo pouch surgery was 26.7 months (13-48). Mean number of bowel movements was 20 per day at the time of presentation. All patients were created a diverting loop ileostomy 3 months prior to redo pouch operation. Intraoperative results showed all 4 patients were diagnosed with retained rectums with 3 patients also having a concomitant pouch twist. Two pouches were excised and a new J-pouch created, while 2 pouches were able to be salvaged through pouch augmentation (video). All patients had diverting loop ileostomies placed at the time of pouch salvage. Re-operative pouch surgery is safe but requires multiple staged-procedures with proper timing and placement of a diverting ileostomy. Patients undergoing pouch salvage must be informed of the possibility of sub-optimal functional results. Since the trend in minimally invasive techniques has increased to encompass J-pouch construction, there has been a resurgence of retained rectums and pouch twists that have caused pouch failure, which maybe secondary to a limited view with laparoscopic instruments. Special attention should be paid to avoid leaving remnant rectum behind and mesenteric twist during minimally invasive pouch surgery.
P-025 Young Investigator Metastatic Crohn's Disease of the Vulva: A Diagnostic Challenge
Al-Chalabi Ahmed, Sodeman Thomas, Lay Roberta, Nawras Ali. University of Toledo Medical Center, Toledo, Ohio
BACKGROUND: Metastatic Crohn’s disease of the vulva is an extraintestinal cutaneous manifestation that occurs less commonly than fistulizing disease. It can be an underdiagnosed entity as it presents in a similar to fashion to other infectious and non-infectious diseases of the vulva. We present a patient with a long history of Crohn’s disease that was initially diagnosed as Hidradenitis suppurativa and who underwent prolonged unsuccessful courses of antibiotics before starting appropriate treatment, illustrating the diagnostic difficulty especially in the absence of active Crohn’s disease.
RESULTS: A 49 year old female with known Crohn’s disease presented initially to gynecology clinic with vulvar lesions of one month duration. The patient had a history of hypertension, depression and recurrent pulmonary embolisms. Past surgeries included laparoscopic proctocolectomy, ileostomy and cholecystectomy. Home medications were furosemide, warfarin, sertraline, Lisinopril and gabapentin. She has not been sexually active for the past 10 years. She reported painful bilateral nodular vulvar lesions that increased in size and eventually started to discharge despite use of cephalexin prescribed in urgent care. She feels otherwise well since her last gastrointestinal surgery three years ago. She denied diarrhea, bleeding per rectum, abdominal pain, weight loss, nausea or vomiting. On physical exam she was obese and had normal vitals. Ileostomy was intact. There were tender nodular lesions associated with clear discharge as well as few small sized ulcers on the mons pubis and labia majora. Rest of exam revealed no abnormalities. Complete blood count, comprehensive metabolic panel, erythrocyte sedimentation rate and C-reactive protein were within normal. Cultures from lesions showed growth of Citrobacter freundii complex sensitive to trimethoprim-sulfamethoxazole. Cultures for MRSA and screening for human papilloma virus, syphilis, chlamydia and gonorrhea was negative. During the following three months, she continued taking multiple antibiotics with several visits to gynecologist and referral to infectious diseases and gastroenterology clinics. Her vulvar lesions never improved. Suspicion of an extraintestinal manifestation of Crohn’s disease was raised, so she underwent biopsy. This revealed non-caseating granulomas in addition to dilated cystic follicles, some containing keratinous debris, with surrounding lymphoplasmacytic infiltrates and dilated blood vessels in a granulation tissue background. Possible diagnosis of hidradenitis suppurativa was suggested by pathologist. Patient was referred to Medical Center for Vulvar Disease, where biopsy results were reviewed. The expert opinion was more favorable of a Metastatic Crohn’s disease. She was started on adalimumab and topical steroids. On follow up one month later, the patient reported significant improvement of her symptoms. Discussion: Metastatic vulvar Crohn’s disease is very rare. Approximately one hundred cases have been reported in the literature. It is characterized by the presence of noncaseating granulomas in the vulva and should be differentiated from other etiologies of granulomatous lesions. There is probably an association between Crohn’s disease and hidradenitis suppurativa, while both can co-exist, which makes distinguishing between them more difficult.
CONCLUSION(S): Metastatic Crohn’s disease of the vulva can be misdiagnosed as hidradenitis suppurativa. Fortunately, treatment of both conditions can be similar (antibiotics and anti-TNF alpha). Possible common immunopathological pathways need further clarification.
P-026 Prepouch Ileitis - Does It Really Exist Or Is It a Misdiagnosis of Crohn’s Disease?
Hakim Seifeldin, Amin Mitual, Cappell Mitchell. William Beaumont Hospital, Royal Oak, Michigan
A 16-year-old girl presented with diarrhea, bloody bowel movements, abdominal cramps, tenesmus, and failure to thrive. Laboratory analysis revealed WBC=8.1 bil/L, HGB=11.4 g/dL, platelets=207 bil/L, Alk.P.=125 U/L. Other liver function tests and kidney function tests were normal. Colonoscopy and biopsy were consistent with extensive ulcerative colitis (UC). She was started on oral prednisone and infliximab (IFX). Her symptoms improved for few months then she relapsed. Extended release budesonide was added to IFX to control her symptoms. She started to develop IFX antibodies. IFX frequency and dosages were increased with no improvement in symptoms despite therapeutic IFX level. She underwent successful restorative proctocolectomy (RPC) with ileal pouch anal anastomosis (IPAA). She was symptom free for 1 year and then she started to develop persistent abdominal pain, and watery diarrhea (8-10 bowel movements). Stool culture, Clostridium difficile toxin, ova and parasite were negative. Ciprofloxacin and metronidazole were given for pouchitis. The patient symptoms improved partially. Colonoscopy showed moderate inflammation in the distal ileal pouch with some aphthous ulcers. Also, ulcerations were noted in the terminal ileum. Microscopic pathology of the ileal pouch showed chronic active inflammation compatible with pouchitis. Microscopic pathology of the terminal ileum (afferent limb) showed chronic active inflammation and ulceration compatible with prepouch ileitis (PPI). She continued her daily metronidazole and ciprofloxacin, which led to partial improvement of her symptoms. Later on, budesonide was used and azathioprine was added to control her symptoms. The patient is doing well for one year.
RPC and IPAA is the operation of choice for UC when UC is refractory to medical treatment or in those who develop dysplasia or cancer. Pouchitis is the most common complication after RSC and IPAA. PPI occurs when inflammation extends into the afferent limb of the pouch. Some physicians suggested reclassifying PPI as Crohn’s disease (CD) rather than UC with PPI. Inflammation proximal to the pouch has been recently recognized and described as PPI. PPI has distinct pathogenic and histologic features different from CD and it was mentioned that PPI demonstrates morphologic changes similar to pouchitis. The theory that PPI is an extension of inflammatory process of pouchitis is supported by the fact that PPI never occurred without pouchitis. The incidence of PPI is less than 6% from all UC patients who underwent RPC and IPAA. Once PPI is diagnosed, response to antibiotics is less likely, it is more refractory to treatment than pouchitis alone and escalation of treatment should be considered.
1. Shen B, et al. Primary sclerosing cholangitis is associated with endoscopic and histologic inflammation of the distal afferent limb in patients with ileal pouch-anal anastomosis. Inflamm Bowel Dis. 2011;17(9):1890-900.
2. Mclaughlin SD, Clark SK, et al. Incidence and short-term implications of prepouch ileitis following restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis. Dis Colon Rectum. 2009;52(5):879-83.
3. Samaan MA, et al. Incidence and Severity of Prepouch Ileitis: A Distinct Disease Entity or a Manifestation of Refractory Pouchitis? Inflamm Bowel Dis. 2016;22(3):662-8.
P-027 Young Investigator A Rare Case of Crohn’s Disease-Associated Aortitis
Hughes Michelle1; Sahay Tanya 1, Saubermann Lawrence2. 1University of Rochester Medical Center, Rochester, New York, 2University Of Rochester- Division of Gastroenterology and Hepatology, Rochester, New York
RESULTS: A 33 year-old woman with history of Crohn’s disease complicated by enteropathic arthropathies presented with symptoms of complete gastrointestinal obstruction. She had history of ongoing ileocolitis despite therapy with certolizumab. Due to persistent obstruction symptoms, she underwent an uneventful laparoscopic ileocecectomy. On post-operative day number two, she developed fever, chest pain, tachycardia and shortness of breath. Her WBC was elevated to 10 K/microL, with CRP 10 mg/L, total IgG and IgG2 noted to be elevated with normal IgG4 levels. Interferon release assay for tuberculosis was negative. A chest CT revealed ascending aortitis, which was later confirmed with MR angiography. She was started on high-dose corticosteroids and ultimately transitioned to infliximab (5 mg/kg) and subcutaneous methotrexate with resolution of aortitis on follow-up imaging. While her aortitis has remained in remission, her intestinal Crohn’s symptoms and arthralgias are recurring despite recently increasing infliximab dose to 10mg/kg every 6 weeks, with therapeutic levels and no evidence of anti-infliximab antibodies.
CONCLUSION(S): Extraintestinal manifestations (EIM) of inflammatory bowel disease are commonly found in approximately one-third of patients. They typically manifest as peripheral or axial arthropathies, dermatologic manifestations including pyoderma gangrenosum and erythema nodosum, ocular involvement including uveitis or episcleritis, and primary sclerosing cholangiopathy. While very uncommon, there also appears to be some degree of overlap between Crohn’s disease and large vessel vasculitides. Initial evaluation should exclude diagnoses of Takayasu’s arteritis, Behcet’s disease, sarcoidosis, ankylosing spondylitis, and connective tissue disorders. Infectious etiologies such as tuberculosis and syphilis should also be eliminated. Upon exclusion of these disease processes causing aortic inflammation, the diagnosis of a Crohn’s-related EIM should be considered. Only a few cases of aortitis associated with Crohn’s disease have been reported in the literature but this appears to be a very rare phenomenon. Severe cases of aortitis carry the risk of aortic rupture when inflammation is left untreated. Fortunately, aortitis appears to be readily responsive to high dose corticosteroid therapy, as was the case in our patient. If significant valvular disease is present (i.e. severe aortic regurgitation), this may require valvular replacement surgery. Interestingly, there have been reports of Crohn’s-related aortitis developing in the setting of anti-TNF therapy, again requiring corticosteroid therapy for resolution. As such, we will need to monitor our patient closely to detect any signs of recurrent aortitis.
P-028 Early Pouchoscopy Is Not Helpful for Surveillance of Dysplasia in the Ileal Pouch
Torres Esther1, Lojo Juan2; Feliciano Gisela 3, Gonzalez Carmen2. 1UPR Medical Science Campus, San Juan, Puerto Rico, 2University of Puerto Rico School of Medicine, San Juan, Puerto Rico, 3Ponce School of Medicine, Ponce, Puerto Rico
BACKGROUND: Pouch surveillance recommendations for dysplasia after ileal pouch anal anastomosis (IPAA) for ulcerative colitis (UC) have yet to be established. The major determinant for developing pouch cancer is dysplasia or carcinoma prior to colectomy. The aim of this study is to describe the findings of our dysplasia surveillance protocol and to examine the yield of early pouchoscopy (6 months) in detecting dysplasia.
METHODS: This is a retrospective cohort study based on data collection of patients at the UPR IBD clinics with IPAA for UC that consented to participate in a research protocol approved by the UPR Medical Sciences Campus IRB (#1250200). Current practice in our clinics is to start surveillance pouchoscopy 6 months after the pouch is functional, repeat at 12 months and yearly afterwards. A minimum of 6 biopsies of the ileal pouch and 2 of the cuff are evaluated by experienced pathologists using Riddell’s criteria for dysplasia. Data collected includes demographics, medical history and indications for UC surgery, symptoms, pouch function, endoscopic and histologic findings.
Of 120 patients identified, 5 were excluded due to development of Crohn’s of the pouch, and 8 were excluded due to missing data and biopsy results. The total sample for this study was 107 patients. Variables examined were: age, sex, date of diagnosis, date of colectomy, time of follow up, time of detection of pouchitis, time of detection of cuffitis, and time of detection of dysplasia. Data analysis consisted of descriptive statistics using frequencies, means, standard deviations and incidence rate of dysplasia (SPSS, v23).
RESULTS: The study population consisted of 54 males (50.5%) and 53 females (49.5%). The mean age was 37.6 years + 14.5. Nineteen (17.8%) subjects had dysplasia prior to surgery and 3 (2.8%) had colon cancer. Mean follow- up was 87.6 + 60.6 months with a range of 3.2-257.1. Pouch failure occurred in 3 (2.9%), Endoscopic or histologic pouchitis was reported at least once in 93 (88.6%) and cuffitis in 79 (73.8%). Complications included 1 leak, 14 strictures (all successfully dilated), and 1 perianal fistula. Dysplasia in the pouch was reported in 2 patients (1.9%), with a mean time of 47.3 months (range 35-59.6) after surgery. Dysplasia was no longer present on follow-up. Both had dysplasia or carcinoma in situ before colectomy. The incidence rate of dysplasia was 0.0026 per person-year. There was no significant association between pouchitis and dysplasia.
CONCLUSION(S): The incidence rate of dysplasia after IPAA in the study population was very low, and first appeared almost 3 years after the surgery. Our results support starting protocol surveillance pouchoscopies after one year of pouch functionality. This will decrease costs and burden to patients without increasing risk of missing the development of dysplasia. We did not analyze studies performed for evaluation of symptoms, as these are outside the scope of the dysplasia surveillance protocol. The impact of the incidental finding of pouchitis in the management and long-term outcome of the patients is also of interest and should be analyzed.
P-029 Patient Characteristics and Clinical Outcomes in Biologic-Naïve Patients With Crohn’s Disease Initiating Vedolizumab Treatment Early Versus Later After Diagnosis
Patel Haridarshan 1, Raluy-Callado Mireia2, Berger Ariel3, Donaldson Robert4, Bhurke Sharvari3, Khalid Javaria Mona5. 1Immensity Consulting, Chicago, Illinois, 2Evidera, London, United Kingdom, 3Evidera, Waltham, Massachusetts, 4Evidera, London, United Kingdom, 5Takeda Development Centre Europe, Ltd., London, United Kingdom
BACKGROUND: Early use of biologics after diagnosis of Crohn’s disease (CD) may provide an opportunity to modify the natural course of the disease, which subsequently could lead to better outcomes. One such biologic therapy is vedolizumab (VDZ), which is approved in the United States (US) for moderately-to-severely active CD. The objective of this study was to investigate characteristics and key outcomes of biologic-naïve patients receiving VDZ treatment earlier vs. later after diagnosis.
METHODS: Adult patients were selected from the Explorys Universe database (~15% of the US population); had a diagnosis of CD (ICD-9 555.xx); initiated first-line biologic treatment with VDZ between May 2014-February 2016; and had ≥12 months of activity before and after the first VDZ infusion (index date). Patients were stratified based on time between CD diagnosis and VDZ initiation: <2 (“early”) or ≥2 years (“late”). Demographic and clinical characteristics were described at index date, and the proportion of patients experiencing one of the following outcomes during the post-index year: CD-related hospitalizations, surgeries, flares (defined as ≥1 intravenous corticosteroid, CD-related hospitalisation or surgery), and corticosteroid use. Time-to-event analyses for each of the outcomes were performed using Kaplan Meier method and log-rank test to compare early vs. late users.
RESULTS: A total of 122 CD patients initiated first-line biologic treatment with VDZ; mean age was 46 years (standard deviation, SD: 15.6); 56.6% were female. Of these, 47 patients (38.5%) started VDZ early (mean [SD] time from diagnosis: 0.8 [0.6] years) and 75 (61.5%) started late (5.9 [3.2] years). Demographic characteristics of early vs. late users were similar, but early users had lower mean Charlson Comorbidity Index scores (0.4 vs. 1.3; P=0.003). Pre-index use of non-biologic therapies was slightly higher among early vs. late users (5-ASA: 25.5% vs. 20%; CS: 68.1% vs. 64%; and IM: 27.7% vs. 20%, respectively); active fistulizing disease also was more frequent among early users (12.8% vs. 1.3%; P=0.013). During follow-up, early users were nominally less likely than late users to be admitted to hospital (14.9% vs. 22.7%; P=0.3542); they also had a numerically longer median time to CD-related hospitalization (172 vs. 112 days; P=0.2647). The proportion of patients with surgeries was low in both cohorts (4.3% vs. 4.0%). Early users were less likely to experience flares (21.3% vs. 45.3%; P=0.0113); they also had longer median times to first flare (129.5 vs. 79.5 days; P=0.007), Early users were nominally less likely to use corticosteroids (38.3% vs. 57.3%; P=0.0623); they also had longer median times to first corticosteroid (83.5 vs. 60 days for late users; P=0.0347).
CONCLUSION(S): In real-world clinical practice, patients treated with VDZ therapy <2 years after diagnosis experienced significantly fewer flares and prolonged time to first corticosteroid use compared to those treated ≥2 years from diagnosis. A trend towards fewer CD-related hospitalizations was also observed among early users of VDZ. These results indicate there may be benefits of early intervention with VDZ. Future studies should focus on long-term impact of earlier intervention with VDZ therapy.
P-031 Ustekinumab Provides Steroid-Sparing and Perianal Improvement in IBD Patients: Single Center Experience
Krugliak Cleveland Noa 1, Normatov Inessa1, Buisson Anthony2, Glick Laura1, Zmeter Nada1, El Jurdi Katia1, Yvellez Olivia1, Pekow Joel3, Cohen Russell D.3, Rubin David T.4. 1University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, Illinois, 2 University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, Illinois, 3University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, Illinois, 4University of Chicago Medicine, Chicago, Illinois
BACKGROUND: Ustekinumab (UST), a monoclonal antibody against the p40 subunit of IL-12 and IL-23, is FDA approved for the treatment of plaque psoriasis and moderate to severe Crohn’s disease (CD). We report our experience with this therapy in our inflammatory bowel disease (IBD) population before and after FDA approval. We previously reported (ACG 2017, Orlando) clinical response and remission rates that were similar to the pivotal trials. Here we describe rates of steroid free remission and perianal improvement.
METHODS: We searched our IRB-approved electronic IBD registry for patients who received UST between Sept 2013 (date of psoriasis approval) and May 1, 2017. This included IBD patients who received off-label CD dosing at the approved psoriasis doses of 45 mg or 90 mg SC at weeks 0, 4 followed by 45 mg or 90 mg SC q12 weeks, and those who received the approved CD doses of weight-based IV loading (260 mg, 390 mg, or 520 mg) followed by 90 mg SC q8 weeks. Patient demographics and medications were reviewed. Steroid-sparing was defined as a patient who was receiving any formulation of steroids at the time of UST initiation and off steroids by 6 month follow-up. All steroids were converted to prednisone equivalents. Taper schedule was per MD discretion. Patients with perianal fistulas at UST initiation were reviewed for improvement at 6 month follow-up by standard clinical assessment (cessation of drainage and no abscess).
RESULTS: We identified 74 patients (57% female) who were prescribed UST at our center: 68 CD, 5 IPAA, 1 IBD-U, median CRP=6 (range 0-165). Mean age at diagnosis 24.8 (SD=1.9); mean age at UST initiation 28 (SD 13.9); median duration of disease at UST initiation was 10.7 yrs (0.9-45.3). 44 (51%) patients with ileocolonic CD and 29 (39%) with perianal disease. 3 (4%) current smokers. All patients but one had failed anti-TNFs prior to UST. 13 (18%) were on concomitant 6-MP and 20 (28%) on MTX. 38 (51.3%) were on steroids at the time of UST initiation (mean daily dose of prednisone equivalent=24mg, SD=15.5). 17 (45%) were steroid-free by 6 month follow-up. 10/16 (62.5%) patients with active perianal fistulas at baseline improved by 6 month follow-up.
CONCLUSION(S): In this real-world experience with UST at a single center pre- and post-approval for CD, we demonstrate a high rate of steroid-sparing as well as a high rate of improvement of draining perianal fistulas.
P-032 Beliefs About Medications in IBD
Jelsness-Jørgensen Lars-Petter1, Bernklev Tomm2. 1Østfold University College, Halden, Norway, 2Vestfold Hospital Trust, Skien, Norway
BACKGROUND: Non-adherence to medication is a well-known problem in patients with Inflammatory Bowel Disease, with prevalence rates ranging from 7-77% for oral medications , and 17-29% for biologics . Factors such as total daily dose, administration route, psychological problems and younger age have been identified as predictors of non-adherence. In contrast, there is a paucity of information regarding the medication beliefs held by people with IBD. The aim of this study was to investigate the beliefs about medications expressed by patients with IBD, and to investigate if these beliefs were associated with fatigue, depression, anxiety, and self-efficacy.
METHODS: Patients from nine hospital outpatient clinics in Norway, were recruited as part of the 1-Year follow-up of the Vitality-study . The Belief about Medicines Questionnaire (BMQ-specific) was used, consisting of two 5-item scales assessing patients’ beliefs about the necessity of medication and their concerns about potential adverse effects of taking it. The score range is 5-25, where a higher score indicates higher necessity beliefs or more medication concerns, respectively. Fatigue was measured with the Fatigue Questionnaire (FQ), including both physical (PF), mental (MF) and total (TF) fatigue. A higher score indicates more fatigue. Symptoms of anxiety and depression were measured with the Hospital Anxiety and Depression Scale (HADS-A and D). Higher HADS score indicate increased symptoms. Self-efficacy was measured using the General Perceived Self-Efficacy Scale (GSE), where a lower score indicates lower self-efficacy.
RESULTS: A total of 67% (274/410) of the original Vitality-study cohort agreed to participate at the one-Year follow-up, of which 94% (257/274) had evaluable data on all outcome measures. Mean BMQ necessity score was 18.5 (SD 4.3, range 5-25), while mean BMQ-concern score was 12.4 (SD 4.1, range 5-23). Increased HADS-D and physical fatigue were negatively associated with BMC necessity (P<0.001 and P<0.05, respectively). BMQ-concern was higher in patients with lower self-efficacy scores (P<0.001) higher HADS-A scores (P<0.001) and mental fatigue scores (P<0.05). Total fatigue scores were not associated with neither BMQ necessity nor concern.
CONCLUSION(S): In this study, we observed that IBD patients had generally low concerns about their prescribed medication, as well as a high belief in the necessity of these medications. Increased concern was associated with increased anxiety and fatigue scores as well as decreased self-efficacy. A decreased belief in the necessity of IBD medication was associated with increased depression and physical fatigue. Addressing these beliefs through a patient-centered approach in clinical follow-up may potentially also optimise patient adherence to medical treatment in IBD.
P-033 Enteric Infections Among IBD Patients: Results From the Nationwide Emergency Department Sample, 2010-2012
Love Bryan. University of South Carolina, Columbia, South Carolina
BACKGROUND: Studies suggest Clostridium difficile infection (CDI) to be increasingly prevalent in patients with IBD and contribute to significantly worse clinical outcomes compared to non-infected patients with IBD. However, the prevalence and burden of other bacterial, viral, and parasitic infection is not well described. The purpose of this research was to evaluate the morbidity and mortality of enteric infections in patients with IBD using a nationally representative ED database.
METHODS: This was a cross-sectional study of adults with a primary or secondary diagnosis of bacterial, viral, or parasitic enteric infections from 2010 to 2012, identified using ICD-9-CM codes. Data were obtained from the Healthcare Cost and Utilization Project Nationwide Emergency Department Sample (HCUP-NEDS). The primary outcome of interest was IBD-related hospitalization. Secondary analyses included total ED charges and mortality. Analytic weights, provided by HCUP, were utilized to report nationally representative estimates. Chi-squared test for categorical variables and the t-test for continuous variables were utilized to measure associations between IBD and enteric infection diagnoses. Multivariable logistic regression was used to examine the association between enteric infection and hospitalization controlling for IBD diagnosis, age category, weekend admission, sex, and hospital geography. All statistical analyses were performed using Stata, version 15.0 (Stata Inc., College Station, TX) with the threshold for significance set at P<0.05.
RESULTS: A total of 923,399 (weighted) discharges of enteric infection were observed during the 3-year period. IBD diagnosis was present in 3.43% of patients. Annual discharges for enteric infections increased from 2010 to 2012 overall and among IBD patients. In both IBD and non-IBD groups, bacterial (97.84%) infections represented the most common cause of enteritis, followed by viral (1.26%), and parasitic (1.04%) infections. CDI was the most common bacterial enteric infection diagnosis in the non-IBD and IBD groups. Significantly more IBD patients were admitted (95.8% vs. 93.24%; P<0.001) and died (8.63% vs 7.04%; P<0.001) from enteric infections compared with the non-IBD group. The odds of hospitalization for any enteric infection were higher in patients with IBD (adjusted OR=2.69) compared to patients without IBD diagnosis. There was no significant difference in total ED charges.
CONCLUSION(S): Enteric infections increased during the 3-year study period and were associated with significant morbidity and mortality among patients with IBD. Bacterial infections were reported more often than viral or parasitic infections, and Clostridium difficile was the most frequently diagnosed enteric pathogen.
P-035 Young Investigator Inflammatory Bowel Disease Training During Adult Gastroenterology Fellowship: A National Survey of Canadian Program Directors and Trainees
Gallinger Zane 1, Rumman Amir2, Alghamdi Sarah3, Pivovarov Kevin3, Dubinsky Marla4, Nguyen Geoffrey5, Cohen Benjamin6. 1The Mount Sinai Hospital, New York, New York, 2University of Toronto, Toronto, Canada, 3University of Toronto, Toronto, Canada, 4Cedars Sinai Medical Center, Los Angeles, California, 5Mt Sinai Hospital IBD Centre, University of Toronto, Toronto, Canada, 6Icahn School of Medicine at Mount Sinai, New York, New York
BACKGROUND: Clinical training in inflammatory bowel disease (IBD) is a major component of adult gastroenterology fellowship. As Canadian residency programs adopt a competency-by-design (CBD) training model, there is a need to identify core competencies in IBD training. This study aims to identify priorities and deficiencies in IBD clinical training among residents and program directors (PDs).
METHODS: Using an online and paper based platform, we administered a 15-question PD survey and 19-question trainee survey and assessed 22 proposed IBD competencies. The survey was previously developed and administered to United States gastroenterology trainees and PDs.
RESULTS: Surveys were completed by 9/14 (62.3%) PDs and 44 trainees. Both trainee years were equally represented (22 residents in each year of training). All respondents were based at university teaching hospitals with full time IBD faculty on staff. All training programs surveyed offered an additional year of advanced IBD fellowship training. Dedicated IBD rotations were not offered by over half of training programs, and IBD exposure was most commonly encountered in inpatient rotations. Overall, only 14 (31.2%) trainees were fully satisfied with the level of IBD exposure during training. Thirty-six (81.8%) trainees reported being comfortable with inpatient IBD management, whereas only 23 (52.3%) trainees reported being comfortable with outpatient IBD management. There was a strong concordance between the proportion of PDs ranking a competency as essential and trainee comfort in that area (Pearson’s rho 0.59; P=0.004). Fewer than half of trainees reported comfort in 11/22 (50%) proposed competencies. Identified areas of deficiency included phenotypic and endoscopic classification of IBD, inpatient management of severe active IBD, perianal disease management, monitoring biologic therapy, and extra-intestinal manifestations of IBD.
CONCLUSION(S): Only one-third of Canadian gastroenterology trainees are fully satisfied with the level of IBD exposure under the current training model. Furthermore, several IBD core competencies appear to be inadequately covered during training. Our findings, which parallel previously published US data, highlight the need for additional focus on IBD during gastroenterology fellowship. It is possible that the optimal treatment of patients with IBD may require advanced specialists.
P-036 High-Dosed Intravenous Iron Replacement Therapy for Iron Deficiency Anemia Does Not Hinder Drug-Induced Amelioration of Disease Activity in IBD Patients
Stein Jìrgen 1, Vollmer Stefan2, Klemm Wolfgang3, Nip Kerry4, Weber-Mangal Susanne4, Dignass Axel5. 1Interdisciplinary Crohn Colitis Centre Rhein-Main, Frankfurt/Main, Germany, 2Gastroenterological Practice, Goeppingen, Germany, 3Gastroenterological Practice, Cottbus, Germany, 4Vifor Pharma, Munich, Germany, 5Agaplesion Markus Krankenhaus, Frankfurt, Germany
BACKGROUND: Iron deficiency and iron deficiency anemia (IDA) are common complications in IBD patients, and can seriously affect quality of life, hospitalization rates, and time lost from work. In IBD patients, anemia is caused by chronic blood loss and/or impaired iron intake and absorption. International guidelines recommend intravenous iron supplementation in IBD patients with moderate-severe anemia or intolerance to oral iron. While oral supplements are convenient and relatively inexpensive, they fail to compensate continuous iron loss due to inadequate intestinal absorption in the presence of inflammation. Oral iron intake is associated with gastrointestinal side-effects including abdominal pain and nausea. Moreover, mounting evidence from animal and human studies shows that non-absorbed iron enhances mucosal inflammation. Intravenous iron has been demonstrated to be safe, effective and well tolerated in correction of IDA and maintenance of iron stores in patients with IBD. Intravenous ferric carboxymaltose (FCM; Ferinject® 50mg ferric iron(III)/mL suspension) can be administered in single 15-minute infusions of up to 1,000mg per week. Here, we assess the effect of high-dosed intravenous FCM on inflammatory activity in IBD patients.
METHODS: A prospective non-interventional post-marketing study was performed in 101 centers in Germany to assess efficacy, tolerability, and convenience of Ferinject® in clinical practice. Alongside primary outcomes including response rates and adverse events, changes in clinical disease indices (CDAI/CAI), changes in CRP values, and self-reported disease-related symptoms (fatigue, concentration lack, headache, paleness of mucous membranes, hair loss, (exertional) dyspnoea, sleeping disorders, restless legs syndrome) rated on a severity scale of 1 to 4, were analyzed. Patients were additionally analyzed in subgroups according to baseline CRP levels (<5mg/L, >5mg/L, 5-10mg/L, >10mg/L).
RESULTS: Intravenous FCM was administered to 224 subjects (127 CD; 97 UC). Mean total iron dose over ca. 12 weeks was 1,139mg (range: 100mg-4,800mg). 76.7% of doses were between 500mg and 2,000mg. Concomitant drugs included aminosalicylates (89 patients/46.1%), corticosteroids (84/43.5%), immunosuppressants (36/18.7%), biologics (36/19%), antibiotics (8/4.1%) and antidiarrheics (11/5.7%). Although patients (n=97) with elevated CD or UC activity indices (CDAI ≥150; CAI ≥5) presented with lower mean Hb values at baseline compared to those with normal activity indices, mean Hb levels at end of study (EOS) were similar. Subjects with higher activity indices presented with higher mean CRP values at baseline (6.1mg/L) compared to those with normal activity indices (3.6mg/L). CRP levels decreased significantly during the observation period, falling from 6.4mg/L to 3.5mg/L in mean (median 1.9 -1.0mg/L), indicating a general reduction in inflammatory activity, which was independent of baseline Hb levels. Change in CRP levels was statistically significant in subgroups of patients with high disease activity, CD and UC patients treated with a total dose of 500-1000mg iron, and patients who completed therapy. Amelioration of inflammatory activity as indicated by lower CRP levels was confirmed by reduced mean clinical disease activity indices (CDAI/CAI). Patients in both CRP subgroups showed increases in Hb, s-ferritin and TSAT, but reduced CRP levels and fewer symptoms.
CONCLUSION(S): High-dosed FCM therapy does not appear to inhibit drug-induced amelioration of inflammatory activity in patients with IBD.
P-037 Mucosal Gene Transcript of Tumor Necrosis Factor in Personalized Medicine of Inflammatory Bowel Disease
Goll Rasmus 1, Meyer Renate2, Moe Øystein3, Knut Johnsen3, Gundersen Mona1, Florholmen Jon1. 1University of Tromsoe - The Arctic University of Norway, Tromsoe, Norway, 2University Hospital of North Norway, Tromsø, Norway, 3Finnmarkssykehuset, Hammerfest, Norway
BACKGROUND: In inflammatory bowel disease (IBD) tumor necrosis factor (TNF) plays a pivotal role of mediating inflammation the disease and anti-TNF is an effective drug for treating the disease. We have shown that low mucosal levels of gene transcript of TNF predicted strong effect of anti-TNF, and in Stop studies of anti-TNF, normalization of gene transcript of TNF retrospectively predicted prolonged time to relapse. Aims: to study clinical utility of mucosal gene transcript of TNF alpha in various clinical settings of IBD in predicting future clinical outcome at debut of disease and impact as a stop criteria of anti-TNF treatment, and evaluation of resistance to anti-TNF treatment
METHODS: In the prospective study Advanced Study of Inflammatory Bowel Disease- ASIB study- evaluation of the clinical impact of measurements of mucosal gene transcript of TNF in predicting future clinical outcome at debut of disease at debut of disease, normalized mucosal TNF transcript as a Stop criteria of anti-TNF in patients in clinical remission, and in anti-TNF resistant patients. Patients with normal colonoscopy was used as healthy controls. Gene transcript of TNF was measured by RT-PCR.
RESULTS: In this preliminary ASIB report, in 65 patients of UC the gene transcript of TNF at debut was 2-3 times higher in patients with severe outcomes than in moderate and mild outcomes after one year. In 22 CD patients and 20 UC patients the part of patients still in remission after anti-TNF stop were 82% and 80%, respectively, with a mean observation time of 17 months and 15 months, respectively. In 16 patients resistant to anti-TNF treatment (UC/CD:10/6, infliximab/adalimumab 10/6) the mean gene transcript of TNF was 5 times normal levels in 14 patients, but normal values were observed in two patient with UC.
CONCLUSION(S): Measurements of mucosal gene TNF transcript is of clinical value at debut of disease predicting clinical outcome after 1 year in UC, predicting long term remission when normalized at stop of anti-TNF in UC and CD, and finally, give more insight in understanding of anti-TNF resistance. Our data indicates that measurements of mucosal gene TNF transcript may be of clinical utility in the handling of inflammatory bowel disease including a personalized therapy.
P-038 Vaccinate the Veterans! Immunization Rates in Veterans With Inflammatory Bowel Disease at the James A. Haley Veterans Hospital
Vellanki Meghana1; Rosario Michelle 1, Bromberg David1, Slone Samuel1, Narayanan Shreya1, Foulis Philip2, Chae Soojong1, Laffer Dennis3, Goldsmith Susan4. 1University of South Florida, Tampa, Florida, 2University of South Florida, James A. Haley Veterans Affairs, Tampa, Florida, 3James A. Haley Veterans Affairs, Tampa, Florida, 4James A Haley VA, Tampa, Florida
BACKGROUND: Patients with inflammatory bowel disease (IBD) have a dysregulated immune system and are more susceptible to vaccine preventable illnesses. Additionally, immunosuppressive therapies used in the treatment of IBD further compromise the immune system. As such, lack of recommended vaccinations leads to preventable increased morbidity, mortality, and utilization of healthcare resources. Vaccination rates for IBD patients in the Veteran’s Affairs (VA) healthcare system lag behind national standards.1 Currently, there is variability in vaccination guidelines as well as misperceptions between primary care physicians and gastroenterologists as to who owns the vaccination process. The aim of our project is to assess rates of vaccination in our VA IBD patients compared to national data, and subsequently identify possible interventions to increase these rates.
METHODS: Data was collected from the Veterans’ Affairs data warehouse using sequel code. Information was obtained from January 1, 2007 to December 31, 2016 on veterans at the James A. Haley Veterans’ Hospital with an IBD diagnosis by ICD-9 or ICD-10 code. The inclusion criteria were determined by CDC guidelines and the IBD Cornerstone Checklist for all vaccines2,3. The following vaccines were evaluated: Hepatitis A; Hepatitis B; Pneumococcal (PCV13 &PPSV23); Influenza; Tetanus, diphtheria, and acellular pertussis (Tdap); and Human papillomavirus (HPV). Veterans were classified as high risk patients if they were treated with any one of the following immunosuppressive therapies: Biologics (TNF-inhibitors), disease-modifying anti-rheumatic drugs (DMARDs), or ≥ 14 days of steroids (≥20mg or equivalent Prednisone).
RESULTS: A total of 1,396 veterans met inclusion criteria for the study. The total percent of patients vaccinated is as follows: Hepatitis A 8%, Hepatitis B 12.8%, Pneumococcal 33.4%, Influenza 42.7%, Tetanus 79.6%, and HPV 0%. For the high-risk population, the vaccination rates are as follows: Hepatitis A 17.4%, Hepatitis B 30.2%, Pneumococcal 44.1%, Influenza 46.6%, and Tetanus 85.2%. Vaccination rates obtained from the National Veterans Health Administration (VHA) are as follows: Hepatitis B 3%, Pneumococcal 39%, and Tetanus 23%1.
CONCLUSION(S): Our study shows that while the James A. Haley VA was above the national average in vaccination rates of veterans with IBD compared to the survey of over 62,000 veterans in the National VHA, our veterans were not meeting the optimal vaccination requirements recommended for IBD patients. Higher risk patients were vaccinated at only slightly higher rates than low risk patients. Our future goal is to implement multiple quality improvement interventions in our gastroenterology clinic to meet national guidelines. Using a process map in our clinic, we have identified multiple opportunities for interventions including a vaccination checklist, IBD template notes that follow the IBD Cornerstone checklist, and an EMR order set decision support tool to increase the vaccination rates for Hepatitis A, Hepatitis B, Pneumococcal (PPV23 and PCV13), and Influenza by 20% each at one year after intervention.
1. Pandey N et al. Preventative care for patients with inflammatory bowel disease in the Veterans Health Administration. Medicine. 2016. 95:27.
2. Farraye FA, Melmed GY, Lichtenstein GR, et al. ACG Clinical Guideline: Preventative Care in Inflammatory Bowel Disease. The American Journal of Gastroenterology. 2017; 112:241-258.
3. Cornerstone Health. 2015.
P-039 Factors Influencing Length of Hospital Stay and Hospital Charges in Patients With Inflammatory Bowel Disease: A Five-Year Population Based Study
Eke Ransome1; Tariq Tooba 1, Bystrom Philip1, Chen Andrew2. 1Western Michigan University School of Medicine, Kalamazoo, Michigan, 2Western Michigan University School of Medicine, Portage, Michigan
BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract. The remitting and relapsing condition of patients with IBD requires long term therapy and periodic inpatient management. However, there is paucity of literature regarding factors associated with an increased in-patient length of stay (LOS) and hospital charges among patients with IBD. Hence, the objective of this study is to determine factors associated with prolongation of hospital stay and increased hospital charges in this population.
METHODS: We conducted a five-year retrospective analysis, using the Healthcare Cost and Utilization Project National Inpatient Survey Database, and estimated the national IBD related hospitalizations from 2009 to 2013 in the United States. The main outcome measures were IBD-associated hospitalizations (ICD-9 codes 555.X and 556.X), length of stay, and total hospital charges. A univariate and multivariate analyses of length of hospital stay and total hospital charges were performed while controlling for potentially confounding variables including age, sex, primary payer, hospital type (teaching or non-teaching), hospital size, location (urban or rural), and co-infection with Clostridium difficile. We computed the variance estimates accounting for finite population correction (fpc) factor.
RESULTS: A total of 295,296 IBD related hospitalizations occurred between 2009 and 2013. Sixty-four percent of the cases were ulcerative colitis (UC) and 36% had diagnosis of Crohn’s disease (CD). The majority of IBD hospitalizations were elderly patients ages greater than 60 years (37%), females (57%) and Caucasians (80%). Sixty-nine percent of the admission types were through the emergency department and about 90% of the admissions occurred in urban hospital locations. The median LOS was 3 days (interquartile (IQR) range, 2-6 days) and median hospital charge per patient was $23, 663 (IQR, $13,143-44587). Results from the multivariate analysis showed that – Longer LOSs were significantly associated with CD patients compared to those with UC, elderly patients, males, teaching hospitals, and urban hospital locations (p-values<0.001). Black and Hispanic patients had significantly shorter hospital stays than Caucasians (p-values<0.05). Similarly, there were significantly longer LOSs in those with C. difficile infection compared with those without, and those with Medicare coverage compared with those with private insurance or self-pay (p-values<0.001). Total charges were significantly higher for CD hospitalization compared to UC, other forms of payment (self-pay, private insurance, Medicaid) compared to Medicare coverage, and urban hospital locations than rural hospitals (p-values<0.001).
CONCLUSION(S): Limited data exists regarding factors affecting hospital stay in IBD patients. Hence, further studies are required to investigate into other potential factors since addressing those factors may reduce hospitalisations and healthcare costs. Increased vigilance to prevent Clostridium difficile infection among patients with IBD could improve outcomes as well.
P-040 Do Nurses and Physicians Know How Much Pain and Anxiety Their IBD Inpatients Have?
Weisshof Roni 1, Labas Jennifer2, Hirsch Ayal2, Golan Maya Aharoni3, Conroy Meghan K.4, Micic Dejan2, Rubin David T.5. 1University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, Illinois, 2University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, Illinois, 3University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, Illinois, 4University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, Illinois, 5University of Chicago Medicine, Chicago, IL
BACKGROUND: Pain is a common symptom in patients with inflammatory bowel disease (IBD) which negatively affects their quality of life and can lead to increased health-seeking behavior and changes in psychological status. Anxiety also is associated with IBD, and associated with poor quality of life. Addressing and alleviating IBD patients’ pain and psychological distress are important goals of management, but it is not known whether patients’ subjective reporting of these factors align with physicians’ (MDs) and nurses’ (RN/APNs) assessments. Therefore, we evaluated the correlations of IBD patient pain and anxiety between the patients, RN/APNs and MDs.
METHODS: This study was approved by the local IRB. We approached a convenience sample of IBD patients admitted to the University of Chicago Medicine and asked them to complete visual analog scales (VAS) of their pain severity and anxiety using a range of 0-100, 100 being the worst pain or worst anxiety. Simultaneously, and blinded to the patient’s reports, the patient’s RN/APN and managing IBD MD completed the same VAS scales for the patient. We collected clinical and outpatient/inpatient medication data from the patients’ medical records. We stratified patients for analysis based on reason for hospitalization, type of IBD, age and prior opioid use. We calculated Spearman correlation coefficient (rho) to assess the relationships between these groups.
RESULTS: 48 IBD patients (26 CD, 27 females, median age 28, range 18-62) were enrolled in this study. Of those, 19 (39%) were receiving previous opiate therapy and 40 (83%) received analgesics during their admission. A total of 10 patients (21%) underwent a surgical intervention during their hospitalization. There was no significant difference in pain or anxiety scores based on age, IBD type, opiate use, or surgical intervention. VAS pain assessment by patients and MDs and patients and RN/APNs was highly correlated (r=0.74, P=0; r=0.69, P=0, respectively). The correlations were independent of patient age, disease, or previous exposure to opiates, with the exception of poorer pain correlation between younger patients and MDs (r=0.53, P=0.01). Agreement between MDs and RN/APNs was good (r=0.54 P=0.001). Assessments of anxiety were not correlated among the different groups (r=0.21 for patients with MDs and r=0.29 with RN/APNs).
CONCLUSION(S): There is a significant positive correlation between hospitalized IBD patient perception of pain and that assessed by MDs and RN/APNs, but poor correlation of patient reports of anxiety. These findings have important implications for pain management and better assessments of anxiety in our patients.
P-041 Analysis of Hospital Discharges and Deaths From Nationwide Health Registry of Inflammatory Bowel Disease in Mexico From 2004 to 2015
Sarmiento Andrea 1, Ríos María2, Toledo Joel1, Yamamoto Jesús1. 1National Institute of Medical Science and Nutrition Salvador Zubirán, Mexico City, Mexico, 2National Institute of Public Health, Cuernavaca, Mexico
BACKGROUND: Inflammatory Bowel Disease (IBD) comprises Ulcerative Colitis (UC) and Crohn’s Disease (CD). Its incidence is increasing worldwide; nevertheless, weather this scenario is happening similarly in Mexico is still unknown. The national registries of hospital discharges and deaths include information about diagnosis, sex and age that can be used as an indirect parameter of how the frequency of IBD has distributed and changed throughout the country and across the years. The aim of this study is to analyze the distribution and tendencies of hospital discharges and deaths reported for IBD in Mexico from 2004-2015 and 2004-2013, respectively.
METHODS: Quantitative cross-sectional study. Analysis from secondary data sources through Dynamic Cubes of the General Direction of Health Information (DGIS for its Spanish acronym), using descriptive statistics categorized by diagnosis, age, sex and state. Shapiro-Wilk test was used to analyze data distribution, median and interquartile ranges were used as central tendency measures and Mann-Whitney U test was used to analyze the differences between the first and last years studied.
RESULTS: In 2015, the number of hospital discharges for IBD was 2,069; in 2013, the number of deaths was 60. The first number increased 98.9% from 2004-2015 (P=0.033); the second increased 96.2% from 2004-2011 (P=0.056) and decreased 42.3% from 2012-2013 (P=0.126). Specifically, the number of hospital discharges for CD increased significantly (2004 vs 2015, P=0.009) while for UC, it showed a trend of significance (P=0.051). Regarding the reported deaths, numbers significantly increased for UC (2004 vs 2011, P=0.04) but not for CD (P=0.064). The most frequent age range of hospital discharges for UC and CD was for both sexes between 15-44 years. Men with UC have a second peak between 45-64 years. The diagnosis of UC is two-fold more frequent than CD. From 2004-2015, Mexico City had the greatest number of hospital discharges (4,179; 22.7%), followed by Jalisco (1,822; 9.9%), Nuevo León (1,204; 6.5%), Coahuila (978; 5.3%) and Chihuahua (892; 4.8%). From 2004-2013, Veracruz had the greatest number of deaths reported (273; 38.2%), followed by Chihuahua (48; 6.7%), Chiapas (36; 5%), Yucatán (30; 4.2%) and San Luis Potosí (24; 3.4%).
CONCLUSION(S): Hospital discharges for IBD in Mexico are increasing significantly, especially those reported for CD; the number of deaths, especially for UC, increased until 2011, but from then on it is starting to decrease. IBD affects Mexican people without gender predominance, affecting more often people between 15 and 44 years; the diagnosis of UC is two-fold more frequent than CD. Mexico City has the greatest number of reported hospital discharges, while Veracruz has reported the greatest number of hospital deaths for this cause. The states with a greater number of hospital discharges are most of them in the north of Mexico, while the states with the greatest number of deaths reported are located in the north and south.
P-042 Predictors of Severity in Inflammatory Bowel Diseases
Farinelli Elen1, da Silva Rosemary1, Síbia Carina1, Renosto Fernanda1, de Barros Jaqueline1; Baima Julio 2, Saad-Hossne Rogerio3, Sassaki Ligia4. 1Faculty of Medicine of Botucatu, Botucatu, Brazil, 2Faculty of Medicine of Botucatu, Botucatu, Brazil, 3Digestive Surgery Department, Unesp Botucatu, Botucatu, Brazil, 4Unesp- FMB, Botucatu, Brazil
BACKGROUND: Inflammatory bowel diseases (IBD), represented by Crohn's disease (CD) and ulcerative colitis (UC), can evolve with disabling symptoms that compromise the patients quality of life. The early identification of severe disease allows a more aggressive therapeutic approach with a lower risk of complications and lower rates of hospitalizations, surgeries and death. The objective of the present study was to identify the variables associated with the need of surgery, hospitalization and death in patients with DC and UC.
METHODS: An observational and retrospective study was carried out collecting data from patients treated at Botucatu Medical School IBD Outpatient Clinic, totalizing 404 eligible patients. We excluded 13 patients with insufficient data. Statistical analysis: descriptive analysis, association tests and multiple logistic regression. Significance level p <0.05.
RESULTS: Two hundred and thirty-seven UC patients were evaluated. Their mean age was 50.72 years (± 16.57), 57.81% were women, 50.26% had pancolitis and 41.81% were in clinical remission. Seventy-one patients (29.06%) required hospitalization and it was associated with C-reactive protein (p <0.0001), pancolitis (P=0.002), smoking (P=0.03), clinical activity (P=0.02), presence of extraintestinal manifestation (OR: 2,04; CI 95%: 1,14-3,55; P=0,01), prednisone use (OR: 3,22; CI 95%: 1,33-7,46; P=0,008), need of surgery (OR: 43.47, 95% CI: 5.71-333.33, P=0.0003), complication (OR: 5.26; 95% CI: 2.11-12, 19, P=0.0003) and death (OR: 15.15, 95% CI: 1.79-125, P=0.01). Fifteen patients (6.32%) underwent partial or total colectomy. The need of surgery was associated with follow-up duration (OR: 1.108, 95% CI: 1.022-1.1201, P=0.01), pancolitis (P=0.03) and hospital admission (OR: 43.47; CI 95%: 5,71-333,333, P=0.0003). Seven patients (2.95%) died and it was associated with the presence of disease activity (p <0.0001), hospitalization (OR: 16.66, 95% CI: 1.79-125, P=0.01), complication (OR: 7.09, 95% CI: 1.49-33.33, P=0.01) and need of surgery (OR: 6.17; 95% CI: 1.09-34.48; P=0.03). One hundred and fifty-four patients with CD were assessed. The mean age was 45.64 years (± 15.53), 53.25% were women, 54.07% had ileocolonic disease, 34.45% presented stricturing disease, 26.05% had a penetrating disease at presentation and 37.01% had perianal disease. Regarding clinical activity, 57.65% were in clinical remission. Ninety-four (61.04%) were hospitalized and 68 (44.16%) underwent surgery. (P <0.0001), presence of extraintestinal manifestation (OR: 6.25, 95% CI: 2.5-11.11, p <0.0001), need for surgery (P<0.0001) and presence of complication (OR: 4.76, 95% CI: 1.96-10.75, P=0.0004). The need of surgery was associated with perianal disease (p <0.0001), hospitalization (p <0.0001), complication (p <0.0001). Death occurred in 5 (3.25%) patients and it was associated with a personal history of diabetes (OR: 24.39, 95% CI: 3.125-200, P=0.002), extraintestinal manifestation (P=0.01), malnutrition (OR: 50; 95% CI: 5,07-500; P=0,0008) and corticosteroids use (OR: 62.5, 95% CI: 6.66-500, P=0.0004).
CONCLUSION(S): The variables of severity in UC were pancolitis extension, presence of disease activity and the need of surgery. The variables of severity in CD were presence of perianal disease, extraintestinal manifestation and presence of complication.
P-043 The Economic Burden Associated With Inflammatory Bowel Disease Severity
Raimundo Karina 1, Montagut Teresa1, Flores Natalia2. 1Genetech, Inc., South San Francisco, California, 2Kantar Health, San Mateo, California
BACKGROUND: Few studies have used patient-reported outcomes to assess the economic burden associated with inflammatory bowel disease (IBD) and IBD severity. The objectives of this study were to use patient-reported outcomes to examine work productivity loss, healthcare resource use (HRU), and estimated annual direct and indirect costs associated with IBD and IBD severity.
METHODS: Data from the 2015 US National Health and Wellness Survey (N=97,700), a nationally representative, internet-based survey of adults, were used to identify IBD patients with a self-reported diagnosis of Crohn’s disease or ulcerative colitis. Propensity score matching was used to create a non-IBD matched control group (1:1 ratio of IBD patients to general population). IBD severity was self-reported as either mild, moderate, or severe. Cohorts for analysis included: mild IBD (N=620), moderate IBD (N=307), severe IBD (N=93), and non-IBD matched controls (N=1020). Work productivity and activity impairment were assessed via the Work Productivity and Activity Impairment (WPAI) questionnaire. HRU included the number of traditional healthcare provider visits, emergency room (ER) visits, and hospitalizations within the last six months. Direct and indirect costs were annualized and monetized using 2013 Medical Expenditure Panel Survey data and 2013 Bureau of Labor Statistics data, respectively. Post-match, omnibus one-way ANOVAs were used to examine whether outcomes differed by IBD status and severity.
RESULTS: The sample mean age was 46 years; 55% female. Significant differences in WPAI, HRU, indirect costs, and direct costs were observed across IBD severity groups and matched non-IBD controls (all p’s<.001). As pairwise comparisons were not conducted due to low sample size among the severe IBD group, means among IBD severity groups and matched non-IBD controls were assessed descriptively. Respondents with IBD, regardless of severity, exhibited greater economic burden across all measures, relative to matched non-IBD controls. Importantly, there was also a linear trend for WPAI by IBD severity, such that those with moderate or severe IBD (absenteeism Means=23.80; 23.99, presenteeism Means=47.33; 44.65, overall work impairment Means=54.54; 51.74, activity impairment Means=53.45; 55.38) reported more work productivity and activity impairment than mild IBD patients (absenteeism Mean=12.60, presenteeism Mean=27.36, overall work impairment Mean=32.53, activity impairment Mean=34.42). This same trend was observed for HRU, wherein those with moderate or severe IBD (traditional provider visits Means=8.17; 7.87, ER visits Means=1.15; 1.53, hospitalizations Means=.80; 1.06) reported more HRU than mild IBD patients (traditional provider visits Mean=6.64, ER visits Mean=.58, hospitalizations Mean=.43). Similarly, those with moderate or severe IBD incurred almost two times more indirect costs (Means=$27,292; $28,818) than mild IBD patients (Mean=$15,769). Moreover, those with moderate or severe IBD incurred almost three times more direct costs (Means=$24,803; $33,725), due to ER visits and hospitalizations, than mild IBD patients (Mean=$13,422).
CONCLUSION(S): These findings suggest that there is a considerable economic burden associated with IBD and moderate/severe IBD, in particular. Those with moderate/severe IBD, relative to those with mild IBD and those without IBD, demonstrated substantially greater WPAI and HRU, which in turn led to greater indirect and direct costs. Appropriate management of disease may reduce disease severity and potentially reduce costs associated with IBD.
P-044 Clinical and Sociodemographic Characteristics of Inflammatory Bowel Disease in Mexico: A Multi-center and Nationwide Study (EPIMEX-IBD)
Sarmiento Andrea 1, Toledo Joel1, Bozada Katya1, Valenzuela Jesús2, Jaramillo Christian3, Angulo Felipe4, Casanova Azucena5, Bermúdez Emilio6, Yamamoto Jesús1. 1National Institute of Medical Science and Nutrition Salvador Zubirán, Mexico City, Mexico, 2Hospital Civil de Guadalajara Dr. Juan I. Menchaca, Guadalajara, Mexico, 3Hospital General Regional 110 IMSS, Guadalajara, Mexico, 4Hospital Regional de Alta Especialidad de la Península de Yucatán, Mérida, Mexico, 5Hospital General de México Dr. Eduardo Liceaga, Mexico City, Mexico, 6Hospital General de Zona 25 IMSS, Mexico City, Mexico
BACKGROUND: The global incidence of Inflammatory Bowel Disease (IBD), Ulcerative Colitis (UC) and Crohn’s Disease (CD), is increasing. However, there are no epidemiological or descriptive data from a nationwide study in Mexico. The aim of this study is to describe the clinical and socio-demographical characteristics of Mexican patients with IBD from whole country.
METHODS: This is a multi-center study where gastroenterologists and colorectal surgeons were involved from 14 states in Mexico who collected clinical and socio-demographic data of all patients with definitive diagnosis of UC, CD and Indeterminate Colitis (IC) during the period between March and June 2017. Data were analyzed using the statistics program SPSS v.24. A p value <0.05 was considered significant.
RESULTS: A total of 1,101 patients was studied, 908 (82.5%) with UC, 174 (15.8%) with CD and 17 (1.5%) with IC from 14 states in Mexico. Female represented 47.2% and male 52.8%. The median age at the time of inclusion in the study was 46 years. The median age at diagnosis was 37 years. Extra-intestinal manifestations were present in 39.1% of patients with UC and 32.8% with CD. The most frequent extra-intestinal manifestations were: arthralgia (28.3%), arthritis (10.8%), osteopenia (5.8%), osteoporosis (3.9%), sacroiliitis (2.8%), primary sclerosing cholangitis (1.8%) and uveitis (1.5%). Most of the patients were born in the most industrialized States of the country, 21.9% being born in Mexico City; 20.2% in Jalisco; 8.8% in State of Mexico and 4.2% in Nuevo Leon. Patients that received attention at public institutions represented 79.7% of the total sample and those which were treated at private centers only 20.3%. In the case of UC: 52.6% of patients had extensive colitis (E3), 17.4% left-sided colitis (E2), 20% distal colitis and 10% no specified extension. In the case of CD: 34.5% of patients reported the following location: colonic (L2), 29.3% ileo-colonic (L3), 17.2% ileal (L1), 2.9% upper tract involvement (L4) and 16.1% no specified location. Most of the patients were under treatment with 5-aminosalicylates (66.3% and 65.5% respectively), followed by steroids (28.7% and 46% respectively), thiopurines (24.9% and 42% respectively) and anti-TNF therapy (16.2% and 37.4% respectively). In the case of UC, 1.9% required surgical treatment and in the case of CD, 17.8%. Patients with CD required surgical treatment more often compared with those with UC (OR=11.36, IC 95%=6.13-21.06, P=0.000). Employee state was associated with higher risk to have diagnosis of UC compared to CD (OR=1.96, IC 95%=1.40-2.75, P=0.000).
CONCLUSION(S): In this first multicenter study at national level, UC was 6 times more frequent than CD. The most frequent extent of UC was pancolitis, while in CD was colonic location. Socio-demographic and clinical variables were associated with different clinical outcomes in Mexican patients with IBD.
P-045 Visceral Fat Is Increased in Individuals With Crohn’s Disease: A Comparative Analysis With Healthy Controls
Magro Daniela 1, Barreto Maria Rita2, Cazzo Everton3, Machado Julia3, Martinez Carlos Augusto4, Camargo Michel5, Ayrizono Maria de Lourdes3, Kotze Paulo6, Coy Claudio7. 1University of Campinas, Campinas, Brazil, 2Unicamp - Campinas - SP - Brazil, Campinas, Brazil, 3Unicamp, Campinas, Brazil, 4Campinas State University, Santo Andre, Brazil, 5Unicamp - Campinas - SP - Brazil, Campinas, Brazil, 6Colorectal Surgery Unit - Cajuru University Hospital - Catholic University of Parana, Curitiba, Brazil, 7Unicamp, Campinas, Brazil
BACKGROUND: The prevalences of overweight (20-40%) and obesity (15-30%) among individuals with inflammatory bowel disease (IBD) are similar to those observed in the general population. The accumulation of visceral fat is a potentially inflammatory factor because it increases the production of inflammation mediators and free fatty acids. It also may be linked to an increased endotoxinemia associated with the augmentation in the intestinal permeability. It is known that obesity is associated with a chronic inflammatory state, but few studies have evaluated the visceral fat content and its role in individuals with Crohn’s disease (CD). Aim: To compare the nutritional status, body composition and proportion of visceral fat between CD individuals and a control group (CG).
METHODS: A cross-sectional study that enrolled individuals with CD and a CG comprised of healthy volunteers. The stratification according to the nutritional status was carried out by means of the body mass index (BMI). The percentage of body fat percentage (%BF) and the visceral fat (VF) were estimated by means of DEXA (dual energy X-ray absorption). The visceral fat proportion was evaluated by means of the VF/BMI and VF/%BF ratios.
RESULTS: A total of 78 individuals were included. The control group was comprised of 28 healthy subjects aged 35.39±10 years old; 60.7% were women; mean BMI: 23.94±3.34 kg/m2; mean VF: 511.82±448.68 grams(g); mean CRP: 0.81±1.78 ng/mL. The CD group was comprised of 50 patients; 11 (22%) were underweight (BMI:18.20±1.97 kg/m2; %BF: 24.46±10.01; VF: 217.18±218.95g; CRP: 4,12±4,84); 18 (36%) presented normal weight (BMI: 22.43±1.48kg/m2; %BF: 30.92±6.63; VF: 542.00±425.47 grams and CRP:4.40±1.78); 21(42%) were overweight or obese (BMI: 29.48±3.78kg/m2; %BF: 39.91±7.33; VF: 1525.23±672.76 grams and CRP: 1.33±2.06). The VF/BMI ratio was higher in the CD group when compared to CG (32.41 ± 24.63 vs. 20.01±16.23 grams per BMI point; P=0.02); likewise, the VF/%BF was also higher in the CD group (35.21±23.33 vs. 15.60±12.55 grams per percentage point; P<0.001). It means that, in CD subjects, there is a disproportion of visceral fat distribution when compared with CG group.
CONCLUSION(S): Among individuals with CD, BMI presents a direct correlation with the visceral fat content. The fat distribution in the CD Group was disproportionate when compared to the CG. These results indicate the presence of an adiposopathy in CD subjects, which is evidenced by a higher visceral fat tissue volume.
P-046 Healthcare Costs Associated With Oral Versus Intravenous Iron Therapy in IBD Patients With Anemia Or Non-anemic Iron Deficiency in Germany
Stein Jìrgen 1, Haas Jennifer2, Ong Siew-Hwa3, Borchert Kathrin2, Hardt Thomas4, Lechat Elmira3, Nip Kerry5, Foerster Douglas3, Braun Sebastian2, Baumgart Daniel6. 1Interdisciplinary Crohn Colitis Centre Rhein-Main, Frankfurt/Main, Germany, 2Xcenda GmbH, Hannover, Germany, 3Vifor Pharma Ltd, Glattbrugg, Switzerland, 4Vifor Pharma Deutschland GmbH, Munich, Germany, 5Vifor Pharma, Munich, Germany, 6Charite University, Berlin, Germany
BACKGROUND: Iron deficiency with or without anemia (ID/A) is the most common extraintestinal complication of inflammatory bowel disease (IBD), detrimentally impacting quality of life and hospitalization rates and causing considerable healthcare costs. Intravenous (IV) iron has shown clinical benefit compared to oral iron therapy. This study aimed to analyze and compare healthcare outcomes and costs during and after oral vs. IV iron treatment of IBD patients with ID/A in Germany.
METHODS: IBD patients with ID/A were identified by ICD-10-GM codes and new commencement of iron treatment via ATC codes in 2013 within the German Health Risk Institute research claims database. Propensity score matching was performed to balance both treatment groups. Non-observable covariates were adjusted by applying the difference-in-differences (DID) approach. To calculate the DID, pre-index and post-index outcomes were compared for the matched cohorts.
RESULTS: 29,331 IBD patients were identified in the database analysis, of whom approximately 15% had confirmed ID/A. Over 50% of IBD patients with ID/A received no prescription iron replacement therapy. Patients who received IV iron treatment were on average 10 years younger than patients on oral iron (50.13 vs. 40.61 years), and 40% were male. In 2013, 589 IBD patients with ID/A began oral and 442 IV iron treatment. Most IV iron- treated patients received iron(III)hydroxide-polymaltose-complex (62.9%) or iron(III)sodium-gluconate-complex (24.9%). After matching for parameters including age, gender and Charlson Comorbidity Index scores, 380 patients in each treatment group were analyzed. All-cause hospitalizations were significantly lower in the IV iron group compared to the oral iron cohort (37% vs. 48%, P=0.0019). Moreover, fewer ID/A-related hospitalizations were observed in the IV iron group (5% vs. 14%, P<0.001). Mean duration of all-cause hospitalizations was 8.5 days for the IV iron cohort and 7.9 days for the oral iron cohort (P=0.0016), whereas the duration of ID/A-related hospitalizations was considerably shorter for the IV cohort (7.0 vs. 9.6 days, P<0.001). The one-year pre-observation period comparison revealed significant healthcare cost differences between both groups. Before treatment, patients in the IV iron cohort had higher costs in all assessed healthcare cost sectors. After/during treatment (post-index period), however, lower costs were observable for inpatient care, devices and aids as well as sick leave payments compared to patients on oral treatment. After adjusting for cost differences by the DID method, total healthcare cost savings in the IV iron group of €367 were calculated. While higher expenditure for medication (€1,876) was observed in the IV iron group, the inpatient setting achieved most cost savings (€1,887).
CONCLUSION(S): IBD patients receiving IV iron were less frequently hospitalized and incurred lower total healthcare costs compared to patients receiving oral iron. Higher expenditures for pharmaceuticals were compensated by cost savings in other domains.
P-047 The Incidence and Risk Factors of Venous Thromboembolism in Japanese Inpatients With Inflammatory Bowel Disease: A Retrospective and Prospective Study
Ando Katsuyoshi 1, Fujiya Mikihiro1, Nomura Yoshiki1, Ueno Nobuhiro1, Inaba Yuhei2, Sugiyama Yuya1, Iwama Takuya1, Ijiri Masami1, Takahashi Keitaro1, Tanaka Kazuyuki1, Goto Takuma1, Kashima Shin1, Sasajima Junpei1, Moriichi Kentaro1, Mizukami Yusuke1, Yamada Satoshi3, Nakase Hiroshi4, Okumura Toshikatsu1. 1Asahikawa Medical University, Asahikawa, Japan, 2Asahikawa City Hospital, Asahikawa, Japan, 3Kyoto University, Graduate School of Medicine, Kyoto, Japan, 4Sapporo Medical University, School of Medicine, Sapporo, Japan
BACKGROUND: Venous thromboembolism (VTE) has been reported as a major extra-intestinal manifestation in inflammatory bowel disease (IBD) in Western countries. However, the incidence and risk factors of VTE in Asian IBD patients are not fully understood. The aim of this study is to reveal the incidence and risk factors of VTE in Japanese IBD inpatients.
METHODS: Retrospective study; The incidence of VTE in inpatients with IBD (n=340), gastrointestinal cancers (n=557) and other gastrointestinal diseases (n=569) treated at our hospital from 2009 to 2013 was retrospectively investigated. The characteristics and laboratory data of IBD patients with and without VTE were compared. Prospective multicenter study; The incidence of VTE in inpatients with IBD (n=41) was compared with that in inpatients with other digestive diseases (n=30) at 3 gastroenterology centers. The presence of VTE was investigated using enhanced computed tomography and/or ultrasonography at two points (on admission, and one to two weeks later).
RESULTS: Retrospective study; VTE was detected in 7.1% of IBD patients. This rate was significantly higher than in gastrointestinal cancer patients (2.5%) and patients with other gastrointestinal diseases (0.88%). The incidence of VTE in ulcerative colitis (UC) patients (16.9%) was significantly higher than that in Crohn’s disease (CD) patients (3.6%). VTE occurred at catheter indwelling sites and in the cerebral venous sinus and portal vein as well as in the lower limbs. According to a univariate analysis, an older age, central venous catheter, prednisolone, surgery, low serum albumin, high serum C-reactive protein and D-dimer were identified as risk factors. According to a multivariate analysis, >50 years of age and surgery were the only risk factors. The mortality rate associated with VTE was 4.2%. No hemorrhagic complications related to anticoagulant therapy occurred. Prospective multicenter study; The incidence of VTE was markedly higher in IBD patients (17.1%) than in patients with other digestive diseases (3.3%). The incidence of VTE in patients with UC (28.6%) was much higher than in those with CD (5.0%). The seven IBD inpatients with VTE consisted of four patients with VTE detected on admission and three patients with VTE detected after admission.
CONCLUSION(S): VTE was frequently detected in IBD patients, especially those with UC, both on and after admission. The efficacy of prophylaxis against VTE based on risk classification should be investigated in Asian IBD patients.
P-048 Young Investigator Antibiotic and Steroid Use - Risk Factors for Gut Colonization With ESBL Producing Enterobacteria In Ulcerative Colitis Out-Patients
Skuja Vita 1, Pekarska Katrina1, Dauvarte Helena2, Vasuka Elina3, Dobelniece Lauma2, Malina Justine2, Rudzite Dace4, Kalcenaua Agate3, Oscepkova Anastasija3, Krumina Angelika4, Lejnieks Aivars4, Derovs Aleksejs4. 1Riga Stradins University, Riga, Latvia, 2Riga Stradins University, Riga, Latvia, 3Riga Stradins University, Riga, Latvia, 4Riga East Clinical University Hospital, Riga, Latvia
BACKGROUND: Extended spectrum beta-lactamase producing Enterobacteria (ESBL-E) are the most frequently found multi-drug resistant (MDR) microorganisms colonizing the gut of ulcerative colitis (UC) patients. Previous studies from our group suggest that gut colonization with ESBL-E might result in more severe disease activity. Risk factors for gut colonization with ESBL-E in general population are often different than in specific disease groups and to the best of our knowledge have not been studied in UC patients in Europe before. The aim of the study was to determine the possible risk factors for gut colonization with ESBL-E in UC patients.
METHODS: A cross-sectional study was conducted analyzing all patients with clinically, endoscopically and histologically confirmed UC diagnosis previously hospitalized in two largest tertiary medical care centers in Riga, Latvia during a 7-year period (2010 – 2016). Patients participated in out-patient interviews regarding the risk factors for gut colonization with ESBL-E, rectal swabs were obtained and Enterobacteria were cultured and analyzed for ESBL presence according to EUCAST guidelines.
RESULTS: A total of 101 patients with confirmed UC diagnosis, 53.5% (n=54) male and 46.5% (n=47) female patients with the mean age of 44.04 (SD=15.45) years, were enrolled in the study. ESBL-E colonization was found in 11.9% (n=12) of the cases. We found that 5% (n=5) of the patients used antibiotics at the time of testing and 42.6% (n=43) of the patients had used antibiotics during the past 12 months. Patients who were taking antibiotics at the time of testing were more often colonized with ESBL-E – 60% (n=3), comparing to the patients who were not taking antibiotics at the time of testing – 9.2% (n=9), (P=0.011). Such ESBL-E colonization differences were not observed in antibiotic use during the past 12 months. Immunosuppressive therapy, including budesonide, methylprednisolone, azathioprine and infliximab, was administered to 29.7% (n=30) of the patients. Patients who were taking steroids during the past 12 months were more frequently colonized with ESBL-E. Patients taking budesonide 50% (n=2) and methylprednisolone 30.8% (n=4) were more frequently colonized with ESBL-E, comparing to patients who were not taking these medications – 10.3% (n=10) (P=0.016) and 9.1% (n=8) (P=0.024), respectively. Such differences were not observed between patients receiving and not receiving anti-cytokines (infliximab) and calcineurin inhibitors (azathioprine). No statistically significant differences were found in gut colonization rates with ESBL-E regarding patient age, gender, concomitant diseases, surgeries, use of proton pump inhibitors, hospital stay and travel anamnesis during the past 12 months.
CONCLUSION(S): Current antibiotic use and steroid use in the past 12 months might be risk factors for gut colonization with ESBL-E in UC out-patients. Such findings could be clinically relevant and help to implement and improve surveillance strategies for MDR microorganisms in UC patients.
P-049 Using an Inflammatory Bowel Disease Objective Structured Clinical Examination to Assess ACGME Milestones in Gastroenterology Fellows
Zalkin Dana 1, Malter Lisa2, Balzora Sophie1, Weinshel Elizabeth3, Zabar Sondra4, Gillespie Colleen3. 1NYU, New York, New York, 2NYU School of Medicine, New York, New York, 3New York University School of Medicine, New York, New York, 4New York University School of Medicine, New York, New York
BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME) has identified six core competencies in which trainees are expected to demonstrate proficiency. Milestones have been developed to provide a framework for evaluating trainee performance within these competencies. We used an objective structured clinical examination (OSCE) focused on inflammatory bowel disease (IBD) to assess the milestones in gastroenterology (GI) fellows.
METHODS: Ten second-year fellows from six GI fellowship programs participated in a four case OSCE. In the “Transition of Care” case the fellow was to assess a patient’s readiness on the planned transition from child-centered to adult-centered care. In the “Shared Decision Making” case the fellow was to evaluate a patient with Crohn’s disease who would benefit from combination therapy. In the “ER Flare” case the fellow was to triage and suggest management of a flaring ulcerative colitis patient. In the “IBS in IBD” case the fellow was asked to discuss irritable bowel syndrome in the context of quiescent IBD. Previously validated OSCE checklists were used to assess the GI fellows’ performance using a 3- and 5-point behaviorally-anchored Likert Scale. Checklists were scored by the standardized patient. Checklist items were mapped to appropriate ACGME milestones by a GI medical educator. Scores within each milestone were normalized on a scale from 0-9 as utilized by the ACGME in the Next Accreditation System milestone initiative. Fellows were provided feedback on their performance.
RESULTS: The majority of fellows scored between 6 and 9 in the milestones assessing patient care (PC), medical knowledge (MK), interpersonal and communication skills (ICS), professionalism (Prof), and systems-based practice (SBP). Composite average scores for all participants were as follows: PC1 7. 7, PC2 6. 9, MK1 6. 9, MK2 7. 0, ICS1 7. 4, Prof1 7. 6, Prof3 6. 9, and SBP4 6. 4. Fellows scored highest in the “Shared Decision Making” case and scored lowest in the “Transitions of Care” case.
CONCLUSION(S): In this OSCE GI fellows performed well in the majority of milestones evaluated, however areas of less optimal performance were identified, providing areas for future focus in fellow training. The OSCE is a well-validated standardized tool for evaluating trainees, and with appropriate mapping of checklists to ACGME milestones, it can serve as an objective method to assess GI fellows’ progress in the core competencies.
P-050 Novel Regulatory DNA Methylation Features of Relevance for Ulcerative Colitis
Paulssen Ruth, Taman Hagar, Fenton Christopher, Hensel Inga, Anderssen Endre, Florholmen Jon. University of Tromsoe - The Arctic University of Norway, Tromsoe, Norway
BACKGROUND: DNA methylation is considered one of the epigenetic mechanisms believed to play a role in the pathogenesis of ulcerative colitis (UC). The aim of this study was to investigate DNA methylation in treatment-naïve UC and to establish if these epigenetic changes correlate to gene expression. The specific aims of this project are to establish and identify genes and their relevant gene regulation mechanisms important in UC pathogenesis
METHODS: Mucosal biopsies from treatment-naïve UC patients (n=14), and healthy controls (n=16) underwent both, RNA-Seq and DNA Bisulfite-Seq by using the Next Seq550 technology from Illumina. RNA and DNA libraries were prepared with the TruSeq Stranded Total RNA LT Sample Prep Kit from Illumina, and Roche SeqCap Epi CpGiant Enrichment kit. The algorithm package STAR-2.5.2b (http://www.bioconductor.org/) was used for down-stream analysis and transcripts were aligned to human genome assembly GRCH38p.11 (https://www.ncbi.nlm.nih.gov/grc/human/data). Principal component analysis (PCA), Limma, and p-value adjustment methods were used to obtain and characterize a dataset of significantly differentially expressed genes (DEGs). For DNA methylation analyses the Bismark Bisulfite Mapper v0.15.0 (www.bioinformatics.bbsrc.ac.uk/projects/bismark/) was used. To annotate DNA methylation sites, regions of 200 bp downstream and 2000 bp upstream of the transcription start site (TSS) were investigated with the NCBI Genome Browser (https://genome.ucsc.edu/). Gene annotations were performed by using the PANTHER classification system (http://pantherdb.org/), the Kyoto Encyclopaedia of Genes and Genomes (KEGG) (www.genome.jp/kegg/).
RESULTS: The entire transcriptome representing treatment-naïve UC was established by RNA-Seq. Initial Principal Component Analysis (PCA) of the 5000 most variable transcripts revealed a clear distinction between UC and control samples along the first principal component with a 59.6% explained variance. Further analyses revealed 1480 significantly differentially expressed genes (DEGs) with P< 0.05, log2FC> 1.0 of which 50% were differentially DNA methylated whereof 70% correlated with transcriptional levels. Seventy-five of these genes showed DNA methylation at CpG sites in the neighbourhood of their transcription start site (TSS). For four genes, the observed DNA methylation occurred in the absence of CpG islands, and known cis-acting regulatory domains: defensin A6 (DEFA6), olfactomedin 4 (OLFM4), regenerating protein beta 1 (REG1B), and butyrophilin like protein3 (BTNL3).
CONCLUSION(S): This study reveals previously unknown DNA methylation patterns of genes in treatment-naïve UC that are not dependent on known regulatory transcriptional elements. This phenomenon implies novel regulatory features of DNA methylation in UC with genes involved in pro-inflammatory responses and possible antimicrobial activities (DEF6A and REG1B), facilitation of cell adhesion through interaction with lectins and cadherins (OLFM4), and lipid metabolism (BTLN3). Investigation of such players may be useful for the development of epigenetic drugs and may allow new treatment strategies for UC patients in the future.
P-051 Analyzing the Safety Profiles of IBD Biologics
Jow Steven 1, Hutfless Susan2. 1Saba University School of Medicine, Devens, Massachusetts, 2Division of Gastroenterology, Department of Medicine, Johns Hopkins University Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
BACKGROUND: There are four routinely prescribed classes of medications to treat inflammatory bowel disease (IBD): aminosalicylates (balsalazide, mesalamine, olsalazine, sulfasalazine), corticosteroids (budesonide, methylprednisolone, prednisone, prednisolone), immunomodulators (6-mercaptopurine, azathioprine, cyclosporine, methotrexate), and biologics (TNF-alpha antagonists [adalimumab, certolizumab, golimumab, and infliximab] and integrin receptor antagonists [natalizumab and vedolizumab]). Many patients worry about the safety of these medications as all classes except aminosalicylates carry warnings for serious adverse events on the Food & Drug Administration (FDA) labels. The biologic medications are of special concern due to media attention related to fatal cancers associated with use, particularly in boys and young men. We aimed to compare serious adverse events for biologics and other IBD medications with all other FDA-approved medications using adverse events reported to the FDA Adverse Event Reporting System (FAERS). We limited our primary analyses to medications associated with an IBD indication.
METHODS: We queried FAERS for serious adverse events (SAE) using Empirica Signal (Oracle Corp., Redwood Shores, CA) based on reports made to the FDA between January 1998 and March 2017. We customized our disproportionality analysis to calculate and compare the cumulative EB05 values for serious adverse events of all IBD medications since their dates of approval. An EB05 value of 2 indicates that a medication-event frequency is double that of other medication-event pairs in the FAERS database (the EB05 is the lower confidence limit of a Bayesian disproportionality measure). We examined the SAE that are most common and carry the highest EB05 signals for each biologic. Lastly, we compared safety signals of IBD biologics indicated for a gastrointestinal indication versus all other indications. Gastrointestinal indications were selected by using Medical Dictionary for Regulatory Activities (MedDRA), a standardized dictionary of adverse events.
RESULTS: From our analysis comparing cumulative EB05 values of SAE associated with a biologic with the indication of IBD to all other serious adverse events reported to FAERS, infliximab had the highest EB05 signal of 1.53. Adalimumab had the lowest cumulative EB05 value of 0.58. The cumulative EB05 values of corticosteroids, immunomodulators, and aminosalicylates were 1.0, 1.19, and 0.92, respectively. The majority of SAE were gastrointestinal and were present for biologics and other treatment classes. Relaxing the inclusion criteria to include a gastrointestinal indication, instead of an IBD indication, and allowing all indications (including rheumatoid arthritis) resulted in higher EB05 values. The highest cumulative EB05 values were observed for infliximab, vedolizumab, and immunomodulators. The highest safety signal associated with any IBD biologic treatment that was not a known complication of IBD or already listed on the label was listeria meningitis (EB05 38.05) which was only elevated for infliximab. Clostridium difficile (EB05 26.67) was the second highest safety signal and was seen with golimumab.
CONCLUSION(S): Medications to treat IBD, including biologics, are as safe as all other FDA-approved drugs. There was no safety signal associated with any biologic to treat IBD associated with serious adverse events in general. We identified new serious adverse events that were not previously listed on the safety labels of biologics.
P-052 The Influence of Extraintestinal Manifestations on Outcomes of Ulcerative Colitis Patients Undergoing Colectomy
Yuquimpo Kyle, Pourghaderi Poya, Lacy Sean, Wright Barth. Kansas City University of Medicine and Biosciences, Kansas City, Missouri
BACKGROUND: Extraintestinal manifestations (EIMs) are common in Inflammatory Bowel Disease (IBD) patients and vary in severity. The addition of such EIMs can complicate a patient’s clinical course and be a detriment to improved outcomes. Little is known regarding the role EIMs may play in the mortality of Ulcerative Colitis (UC) patients who undergo colectomy, a last-resort procedure performed for severe and debilitating stages of UC. We sought out to describe and determine the effect of EIMs on postoperative outcomes in UC patients undergoing colectomy.
METHODS: This retrospective cohort study uses information from the Healthcare Cost and Utilization Program Nationwide Inpatient Sample (NIS) to identify adult patients (>18 years) from 2008 to 2011. UC patients undergoing colectomy were selected using ICD-9 codes. Patients missing important clinical identifiers and those who had a co-diagnosis of Crohn’s Disease were excluded. EIMs were categorized into musculoskeletal, dermatologic, ophthalmologic, hepatobiliary, and pulmonary groups. Inpatient mortality, hospital length of stay (LOS), and inpatient costs were assessed.
RESULTS: 87,359 patients with a diagnosis of UC were identified, of which 3,967 underwent colectomy. Patients were predominantly Caucasian (83.3%), male (53.6%), and older (mean age 53.4 +/- 18.7). 13.4% had at least one EIM, of which musculoskeletal (polyarthritis, osteoarthrosis, ankyloses spondylitis, osteoporosis) composed the largest subset (6.2%). Female patients were more likely to have an EIM (Odds Ratio, 1.71; 95% Confidence Interval, 1.42-2.06). Prior to adjustment for patient characteristics, UC patients with any EIM undergoing colectomy were shown to have increased mortality risk (OR, 1.59; 95% CI, 1.18-2.12). UC patients with a hematological or musculoskeletal EIM were significantly associated with increased postoperative mortality (OR, 2.18; 95% CI, 1.45-3.27 and OR, 1.54; 95% CI 1.45-2.31, respectively). UC patients with any EIM had longer length of stay (12.8 days vs 16.3 days, P<0.001) and increased cost ($127,332 vs $201,716, P<0.001) when compared to UC patients without EIM.
CONCLUSION(S): UC patients with EIMs undergoing colectomy were found to have higher mortality, longer LOS, and higher cost. For patients with UC requiring colectomy, it is imperative to optimize pre-operative management and emphasize the importance of EIMs in addition to the disease activity in clinical and economic outcomes.
P-053 Young Investigator Evaluation of Crohn's Disease Activity in Pregnant Women: A Tertiary Center Experience
Santos Ana, Lopes Susana, Silva Marco, Peixoto Armando, Moreira Pedro, Macedo Guilherme. Centro Hospitalar de São João, Porto, Portugal
BACKGROUND: The major of IBD disease’s patient are diagnosed in fertile age. The severity of IBD disease activity during pregnancy influences the pregnancy outcomes and so, IBD activity at the time of conception apparently determines the clinical course IBD patients will experience during pregnancy. Some studies revealed that if IBD is controlled at time of conception, the risks of adverse pregnancy outcomes are similar as the general female population; on the other hand, the risk of preterm deliveries, intrauterine growth restriction and low birth weight is higher in women with active IBD. These complications also more often seen in CD patients as compared to UC. In some studies, pregnancy seems to have a beneficial effect in IBD symptoms, mainly when pregnancy occurs during a period of remission. Additionally, it was observed a decrease in Harvey-Bradshaw score in CD patients compared with the disease activity during the previous and the following year. So, with this study, we intend to compare the activity of Crohn disease, using the Harvey-Bradshaw index, during pregnancy with its activity in the previous year and the year before delivery.
METHODS: Retrospective and monocentric study, from a prospectively registered cohort of pregnant women with Crohn Disease, in a tertiary reference hospital, between 1999-2017.
RESULTS: We included 62 pregnancies of 47 pregnant women with a mean pregnancy age of 30,8 ± 4,4 years. 74,2% of patients had a non stricturing, non penetrating disease, 25,8% was medicated with anti-TNF and 6,5% has developed a disease exacerbation requiring corticotherapy. There were 2 cases of abortion, both in patients with no controlled disease in the time of conception. Analysing the disease activity, we recorded that in 33% of cases, the Harvey-Bradshaw index decreased from the year before pregnancy to pregnancy time (P=0,01); furthermore, this score increased when we compared the pregnancy with the year after delivery, in 60% of patients (P<0,001) with step of remission to mild disease in 14% of cases and to moderate disease in 7%
CONCLUSION(S): In this cohort, the activity of Crohn Disease during pregnancy was lower when compared with the time after and before, with a higher number of exacerbations recorded during the year after delivery.
P-054 Ferric Carboxymaltose Therapy in IBD Patients With Iron Deficient Anemia: Real-Life Data From Germany
Stein Jìrgen 1, Vollmer Stefan2, Klemm Wolfgang3, Nip Kerry4, Weber-Mangal Susanne4, Dignass Axel5. 1Interdisciplinary Crohn Colitis Centre Rhein-Main, Frankfurt/Main, Germany, 2Gastroenterological Practice, Goeppingen, Germany, 3Gastroenterological Practice, Cottbus, Germany, 4Vifor Pharma, Munich, Germany, 5Agaplesion Markus Krankenhaus, Frankfurt, Frankfurt/Main, Germany
BACKGROUND: Iron deficiency and iron deficiency anemia are common complications in IBD patients, and can seriously affect quality of life, hospitalization rates, and time lost from work. Anemia in IBD is attributable to chronic blood loss and/or impaired iron intake and absorption. International guidelines recommend intravenous iron supplementation in patients with inflammatory bowel disease, since oral supplements are frequently poorly tolerated and there is increasing evidence that they can exacerbate inflammation. Several intravenous iron preparations are currently available for treatment of IDA. Such formulations differ by complex chemistry and can be grouped into labile, semi-labile and stable iron complexes. Of all the IV iron compounds available, by far the largest number of pharmacology studies, phase I to III clinical trials and controlled clinical trials in IBD patients have been performed with ferric carboxymaltose (FCM). These trials have proved its efficacy and tolerability in IBD-associated anaemia. No safety concerns have been identified. However, published data concerning routine use in daily practice are still limited. This post marketing surveillance (PMS) study was designed and performed to assess the safety and efficacy of FCM in a large cohort of patients under routine daily conditions.
METHODS: A prospective non-interventional post-marketing study was performed in 101 centers in Germany to assess the efficacy, tolerability, and convenience of Ferinject® in clinical practice in a large cohort of IBD patients. Primary endpoints were Hb normalization or increase ≥2g/dL (responders), and normalization of serum ferritin and transferrin saturation. AEs, clinical symptoms and disease activity indices were also analyzed.
RESULTS: 224 subjects (127 CD; 97 UC) were treated. Mean total iron dose was 1,139mg (range: 100mg-4,800mg), with 76.7% of doses between 500mg and 2,000mg. 63.3% of patients responded, while no adverse drug reactions, drug-attributed SAEs or deaths occurred. Mean increases of Hb (10.0g/L at baseline to 12.3g/L at end of study), ferritin (52μg/L to 103μg/L), TSAT (15% to 25%) and serum iron (6.1 to 12.4μmol/L) were significant (P=0.0001). Clinical scores and QoL improved due to massive reduction of anemia symptoms.
CONCLUSION(S): Ferinject®-therapy was proven to be effective and safe in a large cohort of patients with IBD-associated anemia in routine practice. Rapid, high-dose application is convenient for physicians and reduces patients’ time lost from work.
P-055 Young Investigator The Prevalence of Sarcopenia and Its Effect on Prognosis in Patients With Crohn’s Disease
Oh Dong Jun 1, Yoon Hyuk2, Lee Jae Min1, Choi Yoon Jin3, Shin Cheol Min3, Park Young Soo3, Kim Nayoung3, Lee Dong Ho3. 1Department of Internal Medicine and Seoul National University Bundang Hospital, Seongnam-si, South Korea, 2Seoul National University College of Medicine, Seoul, South Korea, Seongnam-si, South Korea, 3Seoul National University College of Medicine, Seoul, South Korea, Seongnam-si, South Korea
BACKGROUND: Crohn's disease is associated with altered body composition, such as low muscle mass, which can affect clinical outcomes. However, there are few studies regarding the effect of sarcopenia on prognosis of Crohn's disease, especially in Asia. In this study, we evaluated the body composition at the initial diagnosis of Crohn 's disease and analyzed the clinical meaning of sarcopenia.
METHODS: This is a retrospective review of medical records of patients who are diagnosed as Crohn’s disease and underwent Computed tomography (CT) within 3 months after diagnosis. L3 vertebral slice at CT was used for segmentation of body composition and identification of sarcopenia. Laboratory tests such as CRP, ESR, albumin were measured. Sarcopenia was defined as an L3 skeletal muscle index (SMI) of <55 cm2/m2 for men and <39 cm2/m2 for women. Outcomes included the need for hospitalization or surgery related to the disease within 1 year after the diagnosis of Crohn's disease and the need for use of biologics within 1 year or steroid use within 6 months after diagnosis.
RESULTS: Seventy nine patients were included. The mean age at diagnosis was 25.9 (± 11.3) years old, 59 (74.7%) were male, and 64 (82%) were diagnosed as sarcopenia. CRP and ESR showed a tendency to decrease inversely with SMI (CRP: r=-0.24, P=0.034, ESR: r=-0.33, P=0.008) and albumin tended to increase in proportion to SMI (r=0.314, P=0.005). No statistically significant predictors were found in the outcomes associated with sarcopenia. 14 patients (21.9%) with sarcopenia and 2 patients (13.3%) with normal group used biological agents within one year after diagnosis. In addition, 11 patients (17.5%) underwent surgery and 34 patients (53.1%) required hospitalization within one year after diagnosis of Crohn's disease In the Sarcopenia group. In contrast, only 2 patients (13.3%) underwent surgery and 11 patients (17.5%) underwent hospitalization with Crohn's disease in the normal group.
CONCLUSION(S): Approximately 80% of patients with Crohn 's disease were diagnosed as sarcopenia. SMI correlated with blood tests related to the activity of Crohn 's disease such as ESR, CRP, and albumin.
P-057 Young Investigator Frequency of Extraintestinal Manifestations in Patients With Inflammatory Bowel Diseases in Moscow City
Kagramanova Anna, Knyazev Oleg, Lishchinskaya Albina, Fadeeva Nina, Dobrolyubova Ekaterina, Donchenko Irina, Parfenov Asfold. Moscow Clinical Research Centre, Moscow City, Russia
BACKGROUND: Inflammatory bowel disease (IBD) - ulcerative colitis (UC) and Crohn's disease (CD) - is one of the first places in structure of diseases of the gastrointestinal tract, invaliding patients of a socially active age. Many patients with IBD throughout life there are extraintestinal manifestations of the underlying disease that has a negative impact on disability and quality of life of the patient, sometimes to a greater extent than the underlying disease. The incidence of extraintestinal manifestations ranges from 6% to 50%.
Objective: to identify the frequency of extraintestinal manifestations in patients with UC or CD in Moscow City.
METHODS: 1034 patients with UC and CD observed at the office of the mcrpc treatment of IBD for the period from June 2014 to may 2017. Of these, 602 (58,2%) males and 432 (41,8%) women. The age of patients ranged from 26 to 58 years (Me 35 years).
RESULTS: Extraintestinal manifestations were reported in 375 patients (36,3%). We have carried out the analysis, and the sick could have more extraintestinal manifestations during disease. Extraintestinal manifestations were more often observed in patients with CD (264 of the 488 patients, 54.1%) compared to UC patients (123 of 546 patients, 22.5%; P<0,001). Of the 1034 patients with IBD at 275 (26.6%) showed lesions of the joints in the form of peripheral arthritis/arthralgia (16.2% in UC and 10.4% in CD); in 33 patients (3.1%) revealed primary sclerosing cholangitis (PSC) (2.7% in CD and 0.4% in UC), in 36 patients (3.5%) had lesions of the respiratory system (all patients UC); 44 (4,2%) patients of skin lesions in the form of erythema nodosum (2,5% in CD and 1.7% in UC); 32 (3.1%) patients has violations of the blood coagulation system (thromboembolism) (1.1% in CD and 2.0% in UC). 48 patients (4.6%) has some extraintestinal manifestations: 22 (2.1%) patient CD and 5 (0.5%) patients UC has erythema nodosum and peripheral arthritis; 3 (0.29%) patients has erythema nodosum, peripheral arthritis and primary sclerosing cholangitis; 3 (0.29%) patients has erythema nodosum, peripheral arthritis and uveitis; 7 (0.67%) patients has erythema nodosum, peripheral arthritis and lesions of the respiratory system; 3 (0.29%) patients has erythema nodosum, peripheral arthritis and uveitis; 5 (0.5%) patients has pyoderma gangrenosum, peripheral arthritis and thromboembolism.
CONCLUSION(S): Thorough detection and timely diagnosis of extraintestinal manifestations is essential to prevent disability in patients with IBD. Improving diagnosis and differential diagnosis of extraintestinal manifestations and, therefore, early appointment of adequate therapy may prevent the development of severe complications and improve the quality of life in patients with IBD.
P-058 National Trends of Endoscopies Performed in Inflammatory Bowel Disease Patients From 2008 to 2012
Htun Zin Mar 1, Gul Muhammad2, Kyaw May3, Shaukat Nauman4, Imran Muhammad5, Lin Kyawzaw6, Aye Htar Htar7, Lwin Aung Khine8. 1Louis A. Weiss Memorial Hospital, Chicago, Illinois, 2Presence St. Joseph Hospital, Chicago, Illinois, 3Long Island Jewish Forest Hills Hospital, New York, New York, 4Saint Louis University, St. Louis, Missouri, 5Civil Military Hospital, Rawalpindi, Pakistan, 6The Brooklyn Hospital Center, Brooklyn, New York, 7Fayetteville VA Medical Center, Fayetteville, North Carolina, 8University of Medicine 1, Yangon, Myanmar
BACKGROUND: Inflammatory bowel diseases (IBD) are frequent causes of repeated hospital admission and invasive procedures. Endoscopy plays an essential role in diagnosing IBD patients, differentiation Crohn’s disease from Ulcerative Colitis, monitoring disease activities, and providing treatment. In this study, we analyzed the most common invasive procedures done in IBD in-patients nationwide and showed the trend of endoscopic procedures done in those patient during period of 2008 to 2012.
METHODS: We analyzed the invasive procedures performed in 102,822 IBD in-patients using validated International Classification of Diseases, 9th Revision and Clinical Modification (ICD-9M codes) using Nationwide inpatient sample (NIS) from 2008-2012. Percentage of upper GI endoscopy (EGD) with biopsy, colonoscopy and proctosigmoidoscopy (PSS) with closed rectal biopsy were calculated and compared for statistical significance.
RESULTS: Out of 102,822 IBD patients admitted as in-patient nationwide from 2008-2012, 62847 (61. 1%) patients undergo invasive procedures among which 23514 in-patients (37. 4%) were done endoscopies. While the percentage of total endoscopies remain relatively constant over the years (from 36. 8% in 2008 to 37. 48% in 2012), frequency of colonoscopies decreases from 27. 6% in 2008 to 26. 13% in 2012 (P<0. 01). However, frequency of EGD with biopsy increases from 7. 30% in 2008 to 8. 58% in 2012 in EGD (P<0. 001) and PSS with closed rectal biopsy increases from 1. 8% in 2008 to 2. 76% in PSS (P<0. 05)
CONCLUSION(S): The data demonstrates that nearly two-thirds of IBD in-patients underwent procedures, with colonoscopy being the most common procedure being performed, followed by EGD as second most common. The decreasing trend of colonoscopy and increasing trend of PSS would emphasize the preference of less invasive procedures over the years or advancement of medical therapy with biologic agents leading to better control of symptoms. Increasing trends of EGD indicates that upper GI involvement might be increasingly prevalent in IBD patients. This study helps us understand the current trends of endoscopic procedures in nationwide level hence help us find ways to reduce morbidity and cost.
P-059 Young Investigator Frequency of Small Intestinal Bacterial Overgrowth (SIBO) in Patients With Ulcerative Colitis Using Hydrogen and Methane-Based Breath Tests With Lactulose
Adame Enrique1, Escobar Salvador1; Olivares Laura 2. 1National Institute of Medical Sciences and Nutrition Salvador Zubirán, Mexico City, Mexico, 2Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Ciudad de Mexico, Mexico
BACKGROUND: Small Intestinal Bacterial Overgrowth (SIBO) is present in different gastrointestinal diseases, especially in the presence of predisposing conditions. The variety of clinical manifestations that comes with SIBO can be similar to irritable bowel syndrome or even an UC relapse. Its frequency appears to be higher in patients with IBD compared to non-inflamed controls, which has been partially attributed to inflammation. There are no previous studies regarding SIBO in Mexican patients with UC, which may differ because of the diet habits, genetic and ethnic background. Thus, hypothesizing no difference between the frequency of SIBO in UC in remission and non-inflamed controls, the goal of this study was to evaluate the frequency of SIBO by means of breath tests in patients with active and remission UC compared to non-inflamed controls.
METHODS: Cross-sectional study in patients with histopathological diagnosis of UC in clinical, biochemical and endoscopic remission (May 0-1) who met criteria for carrying out a hydrogen and methane breath test and were not under antibiotic treatment, 30 cases of UC and 26 non-inflamed controls. Hydrogen increase of 20 parts per million or more from the baseline or a methane increase of 10 parts per million or more and a double peak in the graph of exhalation of hydrogen and methane) were considered SIBO. Demographic and clinical variables were collected. Statistical analysis was performed with SPSS software version 24.
RESULTS: A total of 30 patients with remission UC was studied; mean age 42.5 years with a median of 5 years of UC evolution (range 3 - 9.5); 23 (62.2%) women, 14 (37.8%) men. UC extension by Montreal was E1 in 3 (10%) cases and E3 in 27 (90%). The median fecal calprotectin was 106 μg / g (range: 47.25 to 255.25 μg / g). The frequency of SIBO in remission UC was 50% (15 of 30 patients), with a mean orocecal transit of 120 microparticles per million which is classified as normal. Starting from a baseline of 76.6%, the frequency of methanogenesis was finally universal (100%), nevertheless, none of them reached by this criteria SIBO. There was a significant correlation between gastrointestinal symptoms and gas increase in patients with SIBO (P=0.006). There was no statistically significant difference regarding pharmacological treatment between UC patients with and without SIBO.
CONCLUSION(S): The frequency of SIBO was of 50% in patients with UC in remission, methanogenesis was observed in all patients, which interestingly differs from what has been reported in other countries. Orocecal transit of this sample was normal. It is important to consider SIBO as a cause of gastrointestinal symptoms in patients with UC in clinical remission.
P-060 Young Investigator Correlation of Fecal Calprotectin With Acute Phase Reactants (ESR, CRP) in Mexican Patients With Ulcerative Colitis
Yamamoto Jesús1; Olivares Laura 2. 1National Institute of Medical Science and Nutrition Salvador Zubirán, Mexico City, Mexico, 2Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Ciudad de Mexico, Mexico
BACKGROUND: Ulcerative Colitis (UC) gastrointestinal symptoms have an adequate correlation with endoscopic and biochemical parameters in patients with severe activity. However, the evaluation in patients with clinical remission is insufficient. Fecal calprotectin (FC) is effective in these scenarios, which is a fast and non-invasive test with high sensitivity and specificity. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are used in conjunction with FC to assess disease activity, predict and monitor response to treatment. Objective: To evaluate the correlation of FC with ESR, CRP and clinical activity of patients with UC and its possible association with different clinical, endoscopic and histological outcomes.
METHODS: Observational cross-sectional study. All patients in which who were measured in the INCMNSZ's Intestinal Inflammatory Disease Clinic during the period from August 2016 to June 2017 were included. Demographic, clinical, endoscopic and histological variables were collected. We used the criteria of Truelove and Witts for the evaluation of clinical remission or UC activity. Data analysis was performed through the statistical program SPSS version 24.
RESULTS: A total of 127 patients with a histopathological diagnosis of UC were evaluated, of which 63 (49.2%) were women and 64 (50.8%) were men, with a mean age at diagnosis of 44.2 ± 14.9 years and a median evolution of 7 years. In 100 patients (61.1%) they had pancolitis (E3); 17 (9.9%) left colitis (E2) and 10 patients (6.2%) with proctitis (E1). In 93 (73.8%) they were being treated with 5-aminosalicylates; 14 (11.1%) with immunomodulators; 19 (15.1%) with steroids and 3 (2.4%) with anti-TNF biological therapy. The median fecal calprotectin was 306 ug / g (range: 30-1000). CF levels were elevated with a median of 276.5 ug / g in patients with clinical remission. The levels of CF, ESR and CRP according to clinical activity are shown in Table 1. The correlation between CF and ESR was low (R=0.21, P=0.006) as well as between CF and CRP (R=0.10, P=0.18). CF> 250 ug / g was significantly associated with extraintestinal manifestations (P=0.01, odds ratio=3.3, 95% CI: 1.2 -8.1)
CONCLUSION(S): The correlation between ESR and CRP with CF levels was low suggesting that they are not adequate parameters for the adequate assessment of activity in asymptomatic patients. Fecal calprotectin> 250 was associated with the presence of extra intestinal manifestations.
P-061 History of Clostridium Difficile Infection Is Not Associated With Microscopic Colitis
Redd Walker1; Hunold Thomas 1, Hays Rachel2. 1University of Virginia, Charlottesville, Virginia, 2UVA Health System, Charlottesville, Virginia
BACKGROUND: Microscopic colitis (MC) is a common cause of chronic, watery diarrhea that is most common among older women. Although the pathophysiology is unknown, an association with the use of specific medications has been described in the literature. Case reports have also suggested an association of MC with Clostridium difficile infections (CDI). We hypothesize that a history of CDI would be predictive of the onset of MC. We aim to investigate the possible association of MC with CDI among patients with clinically significant chronic diarrhea by determining whether patients with MC were more likely than patients without MC to have a history of CDI.
METHODS: We performed a retrospective case-control study of all patients who underwent colonoscopy to rule out MC in the setting of clinically significant chronic diarrhea from 1/2012 - 12/2016 at a tertiary care center. In the case arm, there were 127 patients diagnosed with MC, and using propensity score matching, 127 patients with normal biopsy results on surgical pathology were matched based on age and gender. Patients under 18 years old, inpatients, and patients who had undergone Fecal Microbiota Transplantation (FMT) were excluded. Primary outcome was history of CDI. Secondary outcomes included history of celiac disease and the use of medications associated with MC, including NSAIDs, PPIs, and anti-depressants. An odds ratio was calculated for the primary outcome, and binomial logistic regression modeling was used to investigate the association between medications and MC. Statistical analysis and propensity score matching were performed in R using the MatchIt package.
RESULTS: 7 of 127 patients in the case arm and 7 of 127 patients in control arm had a history of CDI (OR=1.00; 95% CI=0.34-2.94). Between the case and control arms, no clinically meaningful differences were observed in age, gender, history of celiac disease, or usage of associated medications. Among case patients with history of CDI, the average age was 71.71 and 85.71% were female. Among control patients with history of CDI, the average age was 66.57 and 57.14% were female. Among case patients without history of CDI, the average age was 60.48 and 72.5% were female. Among control patients without history of CDI, the average age was 60.15 and 75.83% were female. Logistic regression analysis revealed NSAID use as a potential predictor of the development of MC; however, PPI and anti-depressant usage were not predictive of the development of MC.
CONCLUSION(S): History of CDI is not associated with and does not predict MC. Clinicians should not let history of CDI influence the decision of whether or not to obtain a biopsy to rule out MC, as the patients with history of CDI will not be at increased risk of MC. While it is likely that luminal factors play a role in MC, the etiology of MC remains unclear. Notably, the usage of two medications, PPIs and anti-depressants, that have been associated with MC in previous studies were not associated with MC. It may be that these medications are actually more associated with unexplained diarrhea than MC.
P-062 Simplified Daily Assessments of Sleep Quality, Pain and Quality of Life in IBD Patients Correlate with Validated Measures
Andersen Jr. Michael 1, Lei Donald2, Golan Maya Aharoni3, Yvellez Olivia1, Rodriquez Dylan4, Zmeter Nada1, Rubin David T.5. 1University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, Illinois, 2University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, Illinois, 3University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, Illinois, 4University of Chicago Inflammatory Bowel Disease Center, Chicago, Illinois, 5University of Chicago Medicine, Chicago, Illinois
BACKGROUND: Improving health-related quality of life (HRQoL) is a primary treatment goal for patients with inflammatory bowel disease (IBD). Patient-reported outcomes (PROs), such as sleep quality and pain, are aspects of wellbeing that are meaningful to patients and can be used to assess components of HRQoL. HRQoL and PROs in IBD patients have previously been assessed using periodically-administered questionnaires which are limited in research and clinical settings by their length and reliance on subjective recall by patients. We aimed to determine the feasibility and reliability of simplified daily HRQoL and sleep quality data collection in patients with IBD using mobile technology.
METHODS: We conducted a prospective, proof-of-concept study over four weeks. Outpatients with IBD downloaded a proprietary smartphone app (developed by Litmus Health, Austin, TX) for visual analog scales (VAS) and validated instrument completion. Patients were prompted daily with VAS for QoL and sleep quality and the Wong-Baker Faces Pain Rating Scale. VAS is a simple format in which patients use a linear sliding scale between “great” and “very bad.” The Wong-Baker Scale asks patients to rate their pain severity using a spectrum of cartoon faces. At days 1, 14, and 28, patients completed the validated Short Inflammatory Bowel Disease Questionnaire (SIBDQ) and Pittsburgh Sleep Quality Index (PSQI). Mean VAS and Wong-Baker scores were calculated for each patient over four weeks. Pearson correlation coefficients were calculated to assess the level of agreement between mean daily survey scores and validated questionnaires taken at day 28.
RESULTS: 12 patients (9 male, 11 Crohn's disease) participated in the preliminary phase of this study; 11/12 were in clinical remission; 7/12 had poor sleep defined by baseline PSQI score. Overall daily VAS and Wong-Baker survey completion rate was 88%. The correlation between mean QoL VAS scores over four weeks and SIBDQ scores at day 28 was excellent (r=-0.90), and the correlation between mean Wong-Baker pain score and SIBDQ was very good (r=-0.69). The correlation between mean sleep VAS scores over four weeks and PSQI scores at day 28 was good (r=0.55). QoL measured by mean QoL VAS was strongly associated with sleep quality measured by mean sleep VAS (r=0.94).
CONCLUSION(S): Daily longitudinal assessments of HRQoL and sleep quality using mobile technologies in patients with IBD are feasible and reliably correlate with validated periodic instruments. These results have informed a larger study which will incorporate passive data collection methods.
P-063 A Retrospective Evaluation of the Quality of Referrals to IBD Specialist Care and Its Influence on Patient Outcomes
Mathias Holly 1, Heisler Courtney1, Morrison Julia2, Jones Jennifer1. 1QEII Health Sciences Centre, Halifax, Canada, 2Nova Scotia Health Authority, Halifax, Canada
BACKGROUND: IBD is an immune-mediated disease, which includes Crohn’s Disease and Ulcerative Colitis. Because of the health and socioeconomic burden associated with IBD, timely access to specialist care is important. In Canada, specialty gastroenterology (GI) care is accessed only by referral. In order to receive timely care, the referral needs to include key disease-related clinical information. Two-thirds of Canadian specialist physicians surveyed reported a lack of basic information on the initial referral (CMA, 2014). Referrals are often returned to the referring physicians for more information, which is inefficient and costly for patients and physicians. Past GI research has examined the quality of referrals, yet no research has measured how the quality of referrals influences patient outcomes. The main objective was to determine if referrals to the Nova Scotia Collaborative Inflammatory Bowel Disease (NSCIBD) program contain sufficient information to allow accurate triage for timely access to care. Our secondary objective was to determine how the quality of initial referrals to the NSCIBD program inform wait times and disease-related outcomes (e.g. disease flare, hospitalization).
METHODS: This study was a retrospective cohort review of patient referrals for NSCIBD program appointments between August 2016 and June 2017. Inclusion criteria included 1) patient’s first visit to the NSCIBD program for 2) confirmed or suspected IBD. Referrals were excluded if they were for a non-IBD-related concern, an endoscopic test, or a follow up visit. Referrals were evaluated using a data abstraction form containing evidence-based, clinical risk-stratification variables, developed with a luminal gastroenterologist and two IBD nurse practitioners. Based on the provided information, referrals were classified as either low, moderate, or high-quality. 136 referrals were provided a power of 0.8 (P=0.05) to detect a difference in wait times between classifications. Logistic regression was used to determine factors that influenced referral quality. Mann Whitney U was used to compare mean differences in wait times, disease flares, and hospitalizations between high/moderate-quality and low-quality referral from the time of initial referral to first IBD consultation. Spearman’s rho was used to find correlations between patient outcomes and relevant patient factors for both classifications.
RESULTS: In total, there were 9 high-quality referrals (6.6%), 23 moderate-quality referrals (16.9%) and 104 low-quality referrals (76.5%). Quality of referral was significantly influenced by several key factors, including referring provider and legibility of referral. Average wait time for patients with a high/moderate-quality referral (14.1 weeks) was significantly lower than wait time for patients with a low-quality referral (31.9 weeks) (U=1458.00, P=0.042). Wait times for patients with a low-quality referral were associated with hospitalization, disease flare, additional referrals, age, sex, diagnosis, duration of disease, phenotype, past and current medication.
CONCLUSION(S): The majority of referrals received by the NSCIBD program were low-quality and have resulted in a significantly longer wait time for patients referred to the program. Prolonged wait time is concerning given its negative impact on disease-related outcomes. The results of this study suggest that referring physicians require education regarding risk-stratification in IBD and that standardized referral forms would allow for more accurate risk-stratification and triage of patients referred to IBD specialty programs.
P-064 Frequency of Micronutrient Deficiencies in Mexican Patients With Inflammatory Bowel Disease
Sarmiento Andrea, Parra Norma, Ávila José, Gómez Eduardo, Lara Karen, Yamamoto Jesús. National Institute of Medical Science and Nutrition Salvador Zubirán, Mexico City, Mexico
BACKGROUND: Inflammatory Bowel Disease (IBD), which includes Ulcerative Colitis (UC) and Crohn's Disease (CD), carries an increased risk of micronutrient deficiencies, such as Vitamin D (VD), Cobalamine (Cbl), Zinc, and Folic Acid (B9), which sometimes can be related to severity of IBD and increased number of hospitalizations. There are no previous data that describe the frequency of these micronutrients deficiencies in Mexican patients with IBD. The aim of this study is to describe the frequency of VD, Cbl, Zinc and folic acid deficiencies in Mexican patients with IBD.
METHODS: We reviewed medical records of 270 patients with IBD histopathological diagnosis from the IBD Clinic of the National Institute of Medical Science and Nutrition Salvador Zubirán, between January 2014 and June 2017. Clinical and sociodemographical data from the 30 days around the day of the sample collection were registered in a database using SPSS v.24, using the following cutpoints to classify serum levels of each micronutrient: VD insufficiency (21-29 ng/mL), VD deficiency (<20 ng/mL), Cbl deficiency (<180 pg/mL), Zinc deficiency (<60 μg/dl) and folic acid deficiency (<6ng/ml). Statistical analysis was performed using mean and median as measures of central tendency to describe data, and Chi squared, Mann-Whitney U test, Spearman’s correlation and MANOVA were further used accordingly. A value of P ≤ 0.05 was considered statistically significant.
RESULTS: A total of 270 patients were studied, 224 had UC (82.96%) and 46 (17.03%) CD; 156 (57.77%) women and 114 (42.22%) men; with an average age ± standard deviation of 47.77 ± 15.19 at the time of evaluation for this study, with a median (range) of years of evolution of IBD of 10 years (1-43). 225 (83.33%) patients had VD registered measures, from them, 108 (48%) had VD insufficiency and 76 (33.8%) VD deficiency: high smoking rate showed a tendency to statistical significance regarding low VD levels (P=0.052); VD levels where significantly lower when measured during the months of autumn and winter (P=0.004). 159 (58.9%) patients had registered Cbl levels, from them, 22 (13.8%) showed deficient levels; CD patients with deficient levels of Cbl (n=10, 45.5%) had more years of evolution compared to patients with normal levels (10 (6-27 years) vs 5 (1-20 years), P=0.01). Of the 71 (26.29%) patients with zinc serum levels, 5 (7%) presented deficiency. From the 166 (61.48%) patients with folic acid levels, the deficiency was found in 5 (3.01%) of them. No associations were evaluated due to the low number of deficiency cases for zinc and folic acid.
CONCLUSION(S): The frequency of micronutrients deficiencies in Mexican IBD patients was: 48% for VD insufficiency, 33.8% for VD deficiency; 13.8% for Cbl deficiency, 7% for Zinc deficiency and 3.01% for folic acid deficiency. A significant trend of significance was found between high smoking rate and low VD levels (P=0.052); VD levels where significantly lower when measured during the months of autumn and winter (P=0.004). CD patients with deficient Cbl levels had long-term disease duration compared to patients with normal levels (P=0.01).
P-066 Primary Sclerosing Cholangitis Is Associated With Ileocolonic CD and Extensive UC in Patients From Northeast of Brazil
Silva Juliana1, Brito Beatriz1, Fortes Flora Maria2, Pimentel Andréa2, Fontes Jaciane2, Almeida Neogélia2, Surlo Valdiana2, Novais Hemmerson3, Neri Isaac4, Liberato Renata5; Santana Genoile 1. 1Universidade do Estado da Bahia, Salvador, Brazil, 2Hospital Geral Roberto Santos, Salvador, Brazil, 3Universidade do Estado da Bahia, Salvador, Brazil, 4Universidade do Estado da Bahia, Salvador, Brazil, 5Universidade Federal da Bahia, Salvador, Brazil
BACKGROUND: Hepatobiliary manifestations may occur in inflammatory bowel disease (IBD)patients. The aim of this study was to evaluate hepatobiliary manifestations in Crohn’s disease (CD) and ulcerative colitis (UC) patients from a reference center of Salvador, Bahia, Brazil.
METHODS: Cross sectional study, from July 2015 to May 2016, with interviews and review of medical charts in an IBD reference center from Salvador, Bahia, Brazil. The SPSS version 21.0 software was applied for statistical analysis. A P<0.05 was considered statistically significant.
RESULTS: 283 patients, including 53%(150) UC patients and 47% (133) CD patients. The mean age was 44 years old and 60% (171) were female. The hepatobiliary manifestations were present in 18.4%(52) IBD patients (26 CD and 26 UC). In 21.2%(11) patients, the hepatobiliary disorders were detected before the diagnosis of IBD, 59.6% (31) after and 17.3% (10) were diagnosed at the same time.
In UC patients, 17.3% (26) presented proctitis, 44.7% (67) left colitis and 38%(57) extensive colitis, according to Montreal Classification. The hepatobiliary disorders were observed in 17.3% (26) UC patients: non-alcoholic liver disease in 6.7%(10), cholelithiasis in 6.7%(10), primary sclerosing cholangitis (PSC) in 3.3%(5) and hepatotoxicity associated to azathioprine in 2% (3). Among them, 46.2% (12) presented extensive colitis, 38.5% (10) left colitis and 15.4% (4) proctitis.
In CD patients, 19.5% (26) presented ileal, 42.1% (56) colonic and 38.3% (51) ileocolonic involvement. The hepatobiliary manifestations were presented in 19.5% (26) CD patients: cholelithiasis in 7.5% (10), non-alcoholic liver disease in 7.5%(10), PSC in 3% (4), alcoholic liver disease in 0.8% (1), autoimmune hepatitis(AIH) in 0.8%(1), hepatotoxicity related to methotrexate in 0.8% (1). 19.2% (5) presented ileal, 42.3% (11) colonic and 38.5% (10) ileocolonic involvement.
The PSC was presented in 9 IBD patients (4 CD and 5 UC), 77.8% (7) were male. The median age of 42 years old, without statistically significance, according to the t-test. Among them, 5% (5) presented extensive-UC (P<0.05) and 40% (4) ileocolonic CD (P<0.05). The majority of PSC-patients (66.7%) presented clinical remission, according to Lichtiger Index and Harvey-Bradshaw Index. There was one case of PSC/AIH overlap syndrome.
CONCLUSION(S): The frequency of hepatobiliary disorders was similar in both forms of IBD in patients from Salvador, Brazil. The most common nonspecific hepatobiliary manifestations in IBD patients were non-alcoholic liver disease and cholelithiasis. The most common specific hepatobiliary disorder was the PSC, in male patients, with extensive UC and ileocolonic CD involvement.
P-067 Prevalence of Contraindications/Precautions to Tumor Necrosis Factor Alpha Blockers Among Patients With Inflammatory Bowel Disease in the United States
Bhurke Sharvari1, Do Thy2, Donaldson Robert3, Berger Ariel1, Bojic Daniela2, Khalid Javaria Mona4; Patel Haridarshan 5. 1Evidera, Waltham, Massachusetts, 2Takeda, Zurich, Switzerland, 3Evidera, London, United Kingdom, 4Takeda Development Centre Europe, Ltd., London, United Kingdom, 5Immensity Consulting, Chicago, Illinois
BACKGROUND: Tumor necrosis factor alpha blockers (anti-TNFs) are currently the most commonly used biologics for moderately-to-severely active inflammatory bowel disease (IBD). However, these agents have several contraindications and risks, which remain important concerns when assessing eligibility for treatment. The objective of this study was to assess the prevalence of these conditions among IBD patients.
METHODS: Using the United States (US) Explorys Universe electronic health records database, we identified all patients aged ≥18 years diagnosed with Crohn’s disease (CD) (ICD-9-CM 555.x, ICD-10 K50.x) or ulcerative colitis (UC) (ICD-9-CM 556.x, ICD-10 K51.x) from January 1, 2010 to August 2, 2017. The date of the earliest diagnosis was deemed the index date, and all patients were required to have at least 12 months of medical history prior to this date. Demographic characteristics were assessed as of the index date. The percentage of patients with ≥1 encounters with a diagnosis code specific to various known contraindications to anti-TNF therapy (i.e., tuberculosis [TB], hepatitis B, sepsis or abscess, opportunistic infections, heart failure) and/or various cancers (i.e., non-Hodgkin lymphomas, Hodgkin lymphomas, leukemia, melanoma or malignant neoplasms) was assessed within the first year of follow-up and at any time after and including the index date, respectively.
RESULTS: A total of 67,983 IBD patients met all selection criteria, including 36,014 with CD and 32,289 with UC. Mean (standard deviation) age of IBD patients was 51 (17.7) years (25.9% were aged ≥65 years), 59.3% were female, and 85.1% were Caucasian; mean duration of follow-up was ~4 years. Within one year of index date, a total of 15.1% (9,790/64,671) had ≥1 contraindications, including sepsis/abscess (9.3%), heart failure (4.2%), and opportunistic infections (4.0%); 5.2% had cancer. During the entire period of follow-up, 25.3% (17,167/67,983) had evidence of ≥1 contraindications, primarily sepsis/abscess (16.5%), opportunistic infections (8.2%), and heart failure (6.8%); 8.2% had cancer. Nineteen percent had ≥1 contraindications and/or cancer within the first year of follow-up; this increased to 30.2% when assessed using all available follow-up time. Relatively few patients had either TB (0.2%) or hepatitis B (0.3%) at any time during follow-up. Results among CD patients were similar to those among UC patients.
CONCLUSION(S): Approximately one-third of IBD patients in the US have ≥1 contraindications and/or cancer that may limit or delay the use of anti-TNF therapies in clinical practice. Alternative treatment options (e.g. anti-integrin therapy) should be considered for these patients.
P-068 The Expression of MicroRNAs in IBD
Saad-Hossne Rogerio 1, Sassaki Ligia2, Síbia Carina3, Reis Patricia4, Baima Julio5. 1Digestive Surgery Department, Unesp Botucatu, Botucatu, Brazil, 2UNESP/FMB, Botucatu, Brazil, 3Faculty of Medicine of Botucatu, Botucatu, Brazil, 4Paulista State University, Botucatu, Brazil, 5Faculty of Medicine of Botucatu, Botucatu, Brazil
BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are the two major diseases that make up the inflammatory bowel disease (IBD). The major clinical manifestations occur in the gastrointestinal tract, especially in the small intestine and colon. The etiology is multifactorial, with an interaction between individual genetic characteristics, predisposition and environment. These factors must be involved in the modification of the immune response with consequent formation of altered inflammatory response. Studies indicate that several genes, in addition to those involved in the modulation of the immune response, are differentially expressed in patients with CD. vs UC. The discovery of microRNAs (miRNAs) as important regulators of gene expression and their role in human diseases, including inflammatory and chronic degenerative diseases, have indicated miRNAs as ideal candidates for diagnostic biomarkers, prognostics and potential therapeutic targets. An important feature of miRNAs is their stability and easy detection in body fluids. Objectives: To identify deregulated miRNAs in DII and to apply bioinformatic analysis strategies to identify target mRNAs and molecular pathways modulated by miRNAs through meta-analysis of literature data.
METHODS: A meta-analysis was performed for the identification of miRNA expression data in IBD. Inclusion and exclusion criteria were applied and 10 studies were selected, from which relevant miRNAs with increased or decreased and statistically significant expression were collected compared to controls, type and number of analyzed samples (serum, plasma or tissue) with CD and / Or UC, platforms used for analysis of global miRNAs expression and validation of data, author name and date of publication. Significantly deregulated miRNAs in DIIvs. Controls were used in bioinformatic analysis to predict the target mRNAs regulated by these miRNAs. Prediction analyzes of miRNA target transcripts and enrichment of biological functions of the target genes were performed.
RESULTS: The results showed 6 CD miRNAs with increased expression and 51 UC. On the other hand, miRNAs with decreased expression were found 51 CD and 26 UC. The miRNAs that showed the greatest number of interactions with DII deregulated genes were let-7a-5p, let-7b-5p and miR-199a-5p, miR-150-5p, miR-362-3p and miR-224- 5p. In the RCU were -155-5p and miR-24-5p, miR-335-5p and miR-16-5p. Suggesting that they may play an important role in the molecular mechanisms of disease. In addition, the results were used to identify gene interactions and biologic processes with: inflammatory process and response to the immune system. We show that miRNAs and target genes may be useful biomarkers for the development of new therapeutic strategies for patients with IBD.
CONCLUSION(S): Several interrelated genes and miRNAs were identified as potential regulators of gene expression. Such miRNAs and genes may play important roles in the development and progression of inflammatory bowel disease. The miRNAs regulate several target genes and important molecular pathways, knowledge of these altered molecular pathways may be useful for the future development of more accurate treatment strategies for patients with DII.
P-069 Prevalence of Depression in Patients With Inflammatory Bowel Disease from the Gastroenterologist Service at National Medical Center 20 de Noviembre
Rivera Vicencio Yahaira 1, López Goméz Jesús2, Rodriguez Romo Roxana1, Cortes Espinosa Tomas2, Ramos Gómez Mayra3. 1National Medical Center 20 de Noviembre, Mexico City, Mexico, 2National Medical Center “20 de Noviembre” ISSSTE, Mexico, Mexico, 3National Medical Center “20 de Noviembre” ISSSTE, Mexico, Mexico
BACKGROUND: The patients with Inflammatory bowel disease (IBD), often experience important levels of psychological distress. The evidence suggests that psychiatric disorders like the depression are risk factors for an early clinic recurrence and a more severe disease such as, a decrease in the adherence to the treatment and an increase in the disability. The objective was to determine the prevalence of depression in patients with IBD from the gastroenterologist service at National Medical Center 20 de Noviembre.
METHODS: Descriptive, observational and transversal study. Were included patients>18 years old with the diagnosis of IBD by clinical, endoscopic and histopathological criteria that belong to the IBD clinic of The National Medical Center 20 de Noviembre. It was applied a validated survey of depression: Montgomery-Asberg and the clinical activity modified Truelove-Witts and the Harvey Bradshaw index. It was determined mean and standard deviation or median and ranks according to the distribution of the variables. For qualitative variables were calculated percentages. For the correlation between the severity of the IBD and the degree of depression it was determined a Spearman’s correlation, P<0.05 was consider statistically significant.
RESULTS: Were included 30 patients with IBD, the average age: 48.97 + 15.17 years, 20 patients with the diagnosis of Ulcerative Colitis (UC) (66.7%) and 10 of Crohn Disease (CD) (33.3%). Treatment: adalimumab 26.7%, infliximab 33.3%, certolizumab 16.7%, aminosalicylates 16.7% and aminosalicylates plus immunomodulatory drugs: 6.7%. It was determined a prevalence of depression of 60%. (33.3% minor depression, 20% moderate depression and 6.7% severe depression). Regarding the index of clinical activity and the degree of depression in patients with UC: patients with inactive disease, 44.4% have depression, mild activity: 80%, moderate activity: 100%. Regarding the activity of the CD and the severity of depression: remission: 28.6% with depression; mild, moderate and severe activity: 100% of patients have depression. Spearman correlation between the severity of the IBD and the degree of depression: UC: r=0.137, P=0.565 and CD: r= 0.588, P=.074.
CONCLUSION(S): The prevalence of depression determined in this study, was important. This means that the depression is an important factor to consider during the clinical management of patients with IBD. Is important to perform a multicentric study with the objective of increase the number of patients, thus it would be possible to calculate a national prevalence and to determine the importance of the depression in this important population.
P-070 Generating an IBD-Specific Patient-Centric Symptom Score
Obremskey Alexandra 1, Hwang Caroline2, Doctor Jason3, van den Akker-van Marle Elske4, van Deen Welmoed5. 1Keck School of Medicine of USC, Santa Monica, California, 2Keck Medical Center at USC, Los Angeles, California, 3USC Schaeffer Center for Health Policy & Economics, Los Angeles, California, 4Leiden University Medical Center Department of Medical Decision Making, Leiden, The Netherlands, 5USC Gehr Family Center for Health Systems Science, Los Angeles, California
BACKGROUND: To date, no tool exists to quantify inflammatory bowel disease (IBD) symptom burden fully based on the patient’s perspective. Previous measures, such as the Mayo score, are based predominately on physician assessment. However, disease burden should be determined, in large part, by how the patient views their illness and the impact their diagnosis has on their quality of life. As healthcare reform moves towards value-based payments and patient reported outcomes, physicians will be called upon more to demonstrate the value of their care to patients and payers alike. Additionally, cost-effectiveness of current IBD medications, which drive the high cost of IBD care, remains ambiguous. Therefore, we are developing an IBD-specific, preference-weighted symptom score, which will allow for quality of care comparisons across institutions.
METHODS: We conducted three focus groups to identify the four most important IBD-related symptoms and the variation in severity for each. We specifically asked patients about what symptoms they found most bothersome, why those symptoms were significant, and what an IBD flare looks like for them. We asked participants at the conclusion of the focus group to rank the first, second, and third “most important” symptoms to them, as they define importance. The results informed the development of a choice-based conjoint analysis survey which will quantify the relative importance of each symptom and symptom level.
RESULTS: Eight patients, four Crohn’s and four ulcerative colitis patients, participated in the focus groups. Patients prioritized symptoms which most disrupted their daily life and caused significant anxiety. One patient said about urgency, “Doing daily things is difficult when you always have to think, ‘where is the bathroom, and can I get there?’”. Urgency and abdominal pain were highly rated for both those reasons, making it into the top three important symptoms. Blood in the stool was another highly concerning symptom for patients, and usually precipitated presentation to a medical professional. Additional bothersome symptoms were stool frequency, liquid stools, and joint pain.
CONCLUSION(S): Symptoms for IBD patients vary widely in type and severity, but there appear to be a few key symptoms that indicate a patient’s overall symptom burden. There was a consensus that urgency, blood in stool, and abdominal pain are all highly bothersome to patients and disruptive to their lives. Based on these results, a conjoint-analysis survey was developed which will evaluate the relative importance of urgency, abdominal pain, blood in stool, and stool frequency. Stool frequency will be included as it a commonly used indicator of disease activity and severity and was mentioned, although less often, as an important symptom for patients. Interim results are expected in October, 2017.
P-071 Patient Wait Time Recall Accuracy for Gastroenterology Specialty Consultation in Nova Scotia
Heisler Courtney, Mathias Holly, Jones Jennifer. QEII Health Sciences Centre, Halifax, Canada
BACKGROUND: Inflammatory Bowel Disease (IBD) is a chronic disease with lifelong health, social, and economic burden. The province of Nova Scotia (NS) has the highest age-adjusted incidence and prevalence rates of IBD in Canada, with Canada having the highest prevalence rates of IBD in the world. The Canadian Association of Gastroenterology guidelines suggest wait times between two and 16 weeks for those with active IBD symptoms. Despite these guidelines, a 2015 audit of the NS Health Authority revealed that 50% of IBD referrals were seen within 12 weeks and 90% of referrals waiting longer (up to two years). Long wait times can lead to increased anxiety, decreased quality of life, and reduction in patient satisfaction and overall health. Estimating wait times is complex but essential in order to evaluate access to specialty care. Aims: 1) To determine whether patients referred to GI specialty services in NS can accurately estimate the length of time between GP referral and first GI specialty appointment; 2) To examine demographic, disease-related, and system factors which may influence the accuracy of patient wait time estimates.
METHODS: Questionnaires were distributed to patients following their appointment with a luminal GI or IBD nurse practitioner. Patients were asked to estimate their wait time for seeing a GI specialist. They were also asked to report on factors that could influence their wait time recall (geographic locale, age, employment status, completed education, disease severity, and relevant comorbidities). Completed questionnaires were returned and retrospective chart reviews were performed to validate the patients’ responses. Descriptive analyses (means, standard deviations) on disease phenotype, complications and surgeries, current and past medication use, distance travelled to appointment, and perceived acceptability of wait times were completed. Spearman’s correlations were run on wait time estimates and actual wait times to determine level of estimate accuracy.
RESULTS: A total of 70 patients were prospectively enrolled as of July 2017. Forty-three (61.4%) patients were female, with an average age of 45.3 years (SD=20.3 years). When patients were asked to estimate their wait time between referral and seeing a GI specialist, they reported an average of 35.7 weeks. Following retrospective chart reviews, the patient estimates were shown to be conservative. In reality, records showed the average patient waited 39.8 weeks from the time the referral was sent to seeing a GI specialist. Spearman's correlation was used to determine the relationship between patient estimates and referral dates. There was a strong positive correlation between patient estimates and referral dates (rs=0.8, N=67, P<0.0001).
CONCLUSION(S): This study is the first of its kind to look at the accuracy of patient recall of wait times for gastroenterology. The initial pilot data highlights the reality of excessive wait times in NS for patients seeking GI speciality care and suggests that patient wait time recall may be used to provide estimates of specialist wait times for patients with IBD. Future research will look at access to GI care using a healthcare systems mapping approach using patient recall to estimate perceived wait times to better inform clinical care pathways in the province.
P-072 Young Investigator Body Mass Index and Activity Index in Ulcerative Colitis and Crohn's Disease, an Established Association?
Pineda Castillejos Jorge 1, López Goméz Jesús2, Rivera Vicencio Yahaira3, Rodriguez Romo Roxana3, Cortes Espinosa Tomas2, Ramos Gómez Mayra4. 1National Medical Center "20 de Noviembre", Mexico, Mexico, 2National Medical Center “20 de Noviembre” ISSSTE, Mexico, Mexico, 3National Medical Center 20 de Noviembre, Mexico City, Mexico, 4National Medical Center “20 de Noviembre” ISSSTE, Mexico, Mexico
BACKGROUND: Inflammatory bowel disease (IBD) is a pathology of unknown etiology resulting from a combination of genetic, immunological and environmental factors. There are 2 types, ulcerative colitis (UC) and Crohn's disease (CD). Obesity affects the Mexican population with a prevalence of 71.28% in 2012, higher in women (37.5%) than men (26.8%). It has been associated with a proinflammatory state involved in the etiology of IBD. Obesity has increased in parallel with IBD, suggesting a possible environmental link between these conditions. The increase in Body Mass Index (BMI) has been associated with indicators of active disease, however, the association between body mass index and IBD activity is not established.
METHODS: Descriptive, cross-sectional, observational study. 44 patients diagnosed with IBD from the "20 de Noviembre" National Medical Center were included. Anthropometric measures of weight, height, BMI and disease activity index (Clinical activity Modified True-love Witts index and Harvey-Bradshaw index) were taken. Measures of central tendency, standard deviation and distribution ranges of variables were used, and proportions were used for the qualitative variables. For the correlation between BMI and IBD activity, Spearman correlation was used, considering p significant<of.05.
RESULTS: 44 patients with IBD, mean age for UC was 50.81 ± 16.31 years and CD was 41.85 ± 13.20. 31 patients with UC (70.45%), women 16 (51.6%) and 13 patients with CD (29.54%), men 8 (61.5%). Regarding BMI, in UC they were normal weight 10 (32.3%), overweight 12 (38.7%), and obesity 8 (25.8%). In CD, they presented normal weight 8 (61.5%) and overweight 3 (23.1%). In relation to the BMI and the activity index for UC, normal weight presented inactive outbreak 5 (50%) and mild outbreak 5 (50%); overweight: mild outbreak 6 (50%), obesity grade I: inactive outbreak 3 (75%), obesity grade II: inactive outbreak 2 (66.7%) and obesity grade III: mild outbreak 1. In relation to BMI and activity index for CD, patients with normal weight: remission 6 (75%), Overweight with mild activity 2 (66.7%) and obesity grade I: remission 1 and moderate activity 1 (50%). When performing the Spearman correlation between IBD activity and BMI: CUCI, r=-0.218, P=0.24, EC, r=0.240, with P=0.42.
CONCLUSION(S): We suggest a multicenter study that allows us to increase the number of patients and correlation between BMI and clinical activity index to corroborate the trend observed in this study that patients with BMI in normal weight and overweight have a lower disease activity compared in patients with obesity. The results of this work support the need to document BMI at each visit and investigate the impact of obesity on the clinical activity index of the disease.
P-074 Young Investigator Combined Anticytokine and Local Mesenchymal Stromal Cells Therapy Promotes Longer Healing of Simple Fistulas in Patients With Crohn's Disease
Kagramanova Anna 1, Knyazev Oleg2, Dobrolyubova Ekaterina3, Lishchinskaya Albina4, Belyakov Nikita3, Orlova Natalya5, Boldyreva Oxana3, Konoplyannikov Anatoliy6, Parfenov Asfold2. 1Moscow Clinical Research Centre, Moscow City, Russia, 2Moscow Clinical Research Centre, Moscow, Russia, 3Moscow Clinical Research Center, Moscow, Russia, 4Moscow Clinical Research Centre, Moscow City, Russia, 5Moscow Clinical Research Center, Moscow, Russia, 6Medical Radiological Research Center, Obninsk, Russia
BACKGROUND: Mesenchymal stromal cells (MSCs), which have immunomodulatory properties and a large regenerative potential, are now also used to treat fistula Crohn's disease (CD) and perianal fistulas of a different etiology. Aim: compare the effectiveness of combined therapy (local and systemic administration) with MSC, infliximab (IFX) and antibiotics (AB)/immunosuppressors (IS) on the frequency of healing of simple perianal fistulas in CD.
METHODS: 50 patients with perianal lesions were divided into four groups, depending on the method of therapy. The first group of patients (n=12) received MSCs systemically according to the scheme and locally. The second group of patients with CD (n=10) received anticytokine therapy of IFX. The third group of patients with CD (n=14) received AB and IS. The fourth group of patients with CD (n=14) received IFX according to the scheme and local MSCs. In the dynamics, the closure of the external fistula opening was evaluated. Anal and rectosigmoidoscopy was performed at 12, 26, 52 and 104 weeks from the start of therapy.
RESULTS: After 12 weeks among patients of the 1-st group, healing of simple fistulas was noted in 10/12 patients (83.3%), in the 2-nd group, healing of simple fistulas in 8/10 (80.0%) (RR-0.83; 95% CI 0.14-4.9, P=0.72). In the 3-rd group - in 5/14 patients (35.7%) (RR-0.26, 95% CI 0.07-0.97, P=0.04 compared with the first group). In the 4-th group in 13/14 patients (92.8%) (RR-0.90, 95% CI 0.67-1.2, P=0.88 in comparison with the 1-st group). After 26 weeks in the 1-st group healing of simple fistulas was preserved in 8/12 (66.6%), in the 2-nd group - in 7/10 (70.0%) (RR- 1.11, 95% CI 0.32-3.84, P=0.76). In the 3-rd group, in 4/14 patients (28.6%) (RR 0.47, 95% CI 0.2-1.11, P=0.12 compared with the first group). In the 4-th group, 13/14 patients (92.8%) (RR 0.72, 95% CI 0.47-1.1, P=0.23 compared with the 1-st group).
After 52 weeks in the 1-st group, the healing of simple fistulas was preserved in 7/12 (58.3%), in the 2-nd group - in 6/10 (60.0%) (RR-1.25, 95% CI 0,48-3.22, P=0.69). In the 3-rd group, in 2/14 patients (14.3%) (RR-0.49, 95% CI 0.24-0.98, P=0.03 compared with the first group). In the 4-th group, 13/14 patients (92.8%) (RR-0.63, 95% CI 0.38-1.04, P=0.1, compared with the 1-st group). In 104 weeks, among the patients of the 1-st group, fistula closure was maintained in 5/12 patients (41.6%), in the 2-nd group in 5/10 (50.0%) (RR-1.17, 95% CI 0.53-2.55, P=0.96). In the 3-rd group, in 0/14 patients (0.0%) (RR-0.58, 95% CI 0.36-0.94, P=0.01 compared with the first group). In the fourth group, 13/14 patients (92.8%) (RR-0.45, 95% CI 0.23-0.89, P=0.016 in comparison with 1-st group (RR-0, 54, 95% CI 0.28-1.00, P=0.05 in comparison with the 2-nd group).
CONCLUSION(S): Combination anti-cytokine therapy and local mesenchymal stromal cells therapy contribute to the more frequent and prolonged closure of simple fistulas in patients with CD in comparison with other known therapy.
P-075 Combined Stem Cells and Anticytokine Therapy Contributes Decrease in the Degree of Inflammation of the Intestinal Mucosa in Crohn's Disease
Knyazev Oleg1; Fadeeva Nina 2, Khomeriki Sergey3, Kagramanova Anna4, Konoplyannikov Anatoliy5, Lishchinskaya Albina2, Donchenko Irina3, Parfenov Asfold1. 1Moscow Clinical Research Centre, Moscow, Russia, 2Moscow Clinical Research Centre, Moscow City, Russia, 3Moscow Clinical Research Center, Moscow, Russia, 4Moscow Clinical Research Centre, Moscow City, Russia, 5Medical Radiological Research Center, Obninsk, Russia
BACKGROUND: One of the new promising methods of treatment of Crohn's disease (CD) is biological therapy with the use of mesenchymal stromal cells (MSCs) of the bone marrow. In a number of cases simultaneously with MSCs, patients receive concomitant anticytokine therapy. Currently, a new strategy for the treatment of Crohn's disease is deep remission of the disease. Objective: to compare the level of immunobiological and histological markers of inflammation - C-reactive protein (CRP), the index of Geboes (IG) and fecal calprotectin (FCP) - in patients with CD receiving cell therapy of MSC, anticytokine therapy with infliximab (IFX) and combination therapy MSCs of bone marrow and IFX.
METHODS: 67 patients with luminal form of CD in the form of colitis and ileocolitis of moderate severity were divided into groups depending on the therapy. The first group of patients aged 19 to 58 years (Me-29) (n=21) received anti-inflammatory therapy with a culture of MSC 2 million/kg according to the scheme, the second group of patients with CD (n=30) aged 23 to 60 years (Me-31) received IFX, the third group of patients with CD (n=16) aged 20 to 57 years (Me-33) received MSCs+IFX. The level of CRP, PCP and IG was evaluated at 26 weeks from the start of the therapy. The baseline CRP level was 24.0±1.9; 22.5±2.1 and 23.0±2.4 mg/l, respectively. The initial IG in the patient groups was 4.4±0.2; 4.35±0.2 and 4.6±0.3 points, respectively. The baseline FCP level was 804.8±88.8; 848.3±83.9 and 937.5±125.6 mcg/g, respectively.
RESULTS: After 26 weeks from the start of the therapy in the first group of patients, the level of C-RP was 9.8±1.1 mg/l, in the second group - 8.4±1.3 mg/l, in the third - 7.9±0.9 mg/l (P>0.05). After 26 weeks from the start of the therapy the level of FCP in the first group was 88.8 ± 5.3 mcg/g, in the second group - 90.6 ± 6.8 mcg/g, in the third group - 68,8 ±3,3 mcg/g (p <0,05 as compared with the 1-st and 2-nd groups). After 26 weeks from the start of the therapy the level of the IG in the first group was 0.7±0.1, in the second group - 0.66±0.1, in the third group - 0.5 ± 0,06 points (P<0.001 in comparison with the 1-st and 2-nd groups).
CONCLUSION(S): Combined mesenchymal stromal cells and anticytokine therapy contributes to a more pronounced decrease in the degree of inflammation from the intestinal mucosa in Crohn's disease.
P-076 Young Investigator Dynamics of Proinflammatory Cytokines in Patients With Crohn's Disease Who Received Combined Therapy With Mesenchymal Stromal Cells and Azathioprine
Knyazev Oleg1; Kagramanova Anna 2, Fadeeva Nina3, Dobrolyubova Ekaterina4, Noscova Karina4, Konoplyannikov Anatoliy5, Lishchinskaya Albina3, Parfenov Asfold1. 1Moscow Clinical Research Centre, Moscow, Russia, 2Moscow Clinical Research Centre, Moscow City, Russia, 3Moscow Clinical Research Centre, Moscow City, Russia, 4Moscow Clinical Research Center, Moscow, Russia, 5Medical Radiological Research Center, Obninsk, Russia
BACKGROUND: Mesenchymal stromal cells (MSC) are used for the treatment of chronic inflammatory and autoimmune diseases in recent years, including rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). In most cases, together with the MSC, patients receiving concomitant immunosuppressive therapy. It is found that immunomodulatory drugs (azathioprine (AZA), methotrexate, 6-mercaptopurine, infliximab (IPF)), regardless of the concentration, do not affect the viability, differentiation, phenotype, and ability to inhibit proliferation of MSCs peripheral blood mononuclear cells. However, studies conducted by Huang HR et al. It demonstrates that IPF rendered minimal impact on the MSC proliferation, apoptosis and cell cycle, while, azathioprine inhibited cell proliferation and induced apoptosis of MSCs in vitro.
Aim: investigate dynamics of proinflammatory cytokine of patients with Crohn's disease (CD) receiving mesenchymal stromal cells (MSCs) of the bone marrow and azathioprine.
METHODS: 34 patients with inflammatory (luminal) form CD were divided into two groups. The first group of patients aged 19 to 58 years old (Me-29) (n=15) was treated with anti-inflammatory therapy with MSCs culture in combination with AZA. The second group of patients with CD (n=19) aged 23 to 60 years old (Me-31) received MSCs according to the recommended scheme without AZA. To assess the effectiveness of anti-inflammatory therapy was determined by the dynamics of the level of pro-inflammatory interleukins (IL) - TNF-α, IFN-γ and IL-1β at 2, 6 and 12 months from the start of MSC therapy. Initial level of IFN-γ in the 1-st group was 110,4±12,5 pg/ml, in the 2-nd - 450,8±22,4 pg/ml (P<0,05), TNF -α in 1-st group - 13,9±1,9 pg/ml, in the 2-nd - 66,7±14,2 pg/ml (P<0,05), IL-1β in 1-st group – 5,7±0,28 pg/ml, in the 2-nd - 9,2±0,2 pg/ml (P<0,05).
RESULTS: After 2 months of therapy MSCs level of IFN-γ in 1-st group was significantly decreased from baseline and was 86,5±9,1 pg/ml, the 2-nd was 96,9±12,1 pg/ml (between groups P=0,5), TNF-α in 1-st group decreased to 39,6±8,4 pg/ml, in the 2-nd - 56,5±10,7 pg/ml (between groups P=0.2), IL-1β in 1-st group -50,7±9,3 pg/ml, in the 2-nd - 56,2±10,2 pg/ml (between groups P=0,7). After 6 months of therapy MSCs level of IFN-γ in 1-st group decreased and amounted to 79,4±8,5 pg/ml, in the 2-nd - 80,8±7,3 pg/ml (between groups P=0.9), TNF -α in 1-st group decreased to 44,9±6,3 pg/ml, in the 2-nd - 49,7±10,4 pg/ml (between groups P=0,7). IL-1β in 1-st group - 45,6±7,3 pg/ml, in the 2-nd - 54,2±9,2 pg/ml (between groups P=0,45). After 12 months of initiation of therapy MSCs level of IFN-γ in 1-st group decreased and amounted to 90,8±6,5 pg/ml, in the 2-nd - 128,8±12,3 pg/ml (between groups P=0,02), TNF-α in the 1-st group - 78,9±10,5 pg/ml, in the 2-nd - 116,9±13,2 pg/ml (between groups P=0,04), IL-1β in 1-st group - 68,7±8,9 pg/ml, in the 2-nd - 96,9±9,6 pg/ml (between groups P=0,03).
CONCLUSION(S): After one year of observation, combined treatment of AZA and MSC significantly reduces the level of pro-inflammatory cytokines, which may have a more pronounced anti-inflammatory therapeutic effect.
P-077 Young Investigator Comparative Relapse Rate in Patients With Inflammatory Bowel Diseases Receiving Mesenchymal Stromal Cells - 5 Years Of Follow-Up
Knyazev Oleg1; Fadeeva Nina 2, Lishchinskaya Albina2, Konoplyannikov Anatoliy3, Kagramanova Anna4, Dobrolyubova Ekaterina5, Donchenko Irina5, Ruchkina Irina6, Boldyreva Oxana5, Parfenov Asfold1. 1Moscow Clinical Research Centre, Moscow, Russia, 2Moscow Clinical Research Centre, Moscow City, Russia, 3Medical Radiological Research Center, Obninsk, Russia, 4Moscow Clinical Research Centre, Moscow City, Russia, 5Moscow Clinical Research Center, Moscow, Russia, 6Central Research Institute of Gastroenterology, Moscow, Russia
BACKGROUND: Numerous studies have shown that mesenchymal stromal cells (MSCs) have a high potential for differentiation and immunosuppressive properties. Currently under phase I-III clinical trials evaluating the efficacy and safety of MSCs in the treatment of patients with inflammatory bowel disease (IBD) - ulcerative colitis (UC) and Crohn's disease (CD).
Objective: To compare the frequency of relapses and duration of remission for 5 years of follow up in patients with luminal Crohn's disease (CD) and the total defeat of ulcerative colitis (UC) receiving therapy with mesenchymal stromal cells (MSCs), bone marrow
METHODS: We compared the frequency of relapses in patients with luminal form CD (colitis and ileocolitis), with a group of patients with UC (total lesion) receiving MSCs. A group of patients (CD) aged 22 to 56 years (Me-28) (n=24) received MSC culture scheme (0-1-2 weeks, then every 26 weeks). The second group of patients with UC (n=26) aged 20 to 62 years (Me-28) received the culture of MSCs in a similar way. Evaluation of the effectiveness of therapy for relapse frequency was carried out at 12, 24, 36, 48 and 60 months after initiation of therapy.
RESULTS: Among the patients in 1-st group relapse in the 12 months of observation occurred in 2/24 patients (8.3%) in 2 group, relapse occurred in 3/26 (11.5%) (OR-0.72; 95% CI 0,13-3,96, P=0.92). After 24 months in the group of patients (group 1) receiving MSC, relapse occurred in 5/24 (20.8%) in group 2 patients with recurrent disease in 7/26 (26.9%) (OR -0.77; 95% CI 0,13-3,96, P=0.92). After 36 months in group 1 patients with a relapse of the disease in 8/24 (33.3%) in group 2 relapsed in 14/26 (53.8%) (OR-0.62; 95% CI 0, 32-1,21; P=0.24)/ After 48 months in group 1 receiving MSC, relapsed in 11/24 (45.8%) in group 2 relapsed in 18/26 (69.2%) (OR-0.6; 95% CI 0,37-0,97, P=0.048). After 60 months in 1st relapse in 16/24 (66.6%) in group 2 relapsed in 22/26 (84.6%) (OR- 0.63; 95% CI 0,44-0 90, P=0.013).
CONCLUSION(S): MSCs transplantation longer contributes to clinical remission in patients with Crohn's disease luminal shape compared to a group of patients suffering from ulcerative colitis.
P-078 Quality of Life, Anxiety, Depression and Sexual Dysfunction in Patients With Chronic Intestinal Diseases
Andriolli Guilherme1; Baima Julio 2, Yao Tiago1, de Barros Jaqueline3, Saad-Hossne Rogerio4, Sassaki Ligia5. 1UNESP, Botucatu, Brazil, 2Faculty of Medicine of Botucatu, Botucatu, Brazil, 3Faculty of Medicine of Botucatu, Botucatu, Brazil, 4Digestive Surgery Department, Unesp Botucatu, Botucatu, Brazil, 5Unesp- FMB, Botucatu, Brazil
BACKGROUND: "Quality of life" (QoL) has been emphasized to assess the impact of a disease and its treatment in the patient’s life. The QoL of chronic patients is significantly impaired, and it can lead to psychological and social changes, engendering anxiety, depression and other injuries, including sexual dysfunction. The aim of this study is to compare the QoL, the presence of anxious and depressive symptoms, the frequency of female sexual dysfunction and erectile dysfunction, and patient's self-esteem in the following groups: Inflammatory Bowel Diseases (IBD), Functional Bowel Disorders (FBD), Colon Cancer (CC) and Control Group (CG).
METHODS: Cross-sectional study with specific questionnaires application, approved in the Research Ethics Committee (n.1.356.518). Ninety-nine patients with IBD (43 with Ulcerative Colitis and 56 with Crohn's Disease), 35 with FBD (20 with Chronic Constipation and 13 with Irritable Bowel Syndrome), 33 with CC and 150 healthy controls were interviewed. The SF-36 questionnaire was used to evaluate the Quality of Life, the Hospital Anxiety and Depression Scale (HADS) to assess the presence of anxiety and depression, the Rosenberg Self-esteem Scale to study the patients’ self-esteem, the International Index of Erectile Function to evaluate the erectile dysfunction and the Female Sexual Function Index to assess the female sexual dysfunction. Statistical: descriptive and association tests, p <0.05.
RESULTS: The mean age was 38.89 (± 10.15) years in the IBD group; 46.77 (± 15.87) in FBD patients; 62.88 (± 11.46) years in the CC group and 36.26 (± 12.39) in the CG. There was a predominance of women in IBD (56.6%), in FBD (97.1%) and in control (67.33%) groups, p <0.0001. Men had a small predominance in the CC group (51.5%), p <0.0001. The quality of life was impaired in the FBD group, with a significant difference compared to IBD (p <0.001) and control groups (p <0.0001). The prevalence of anxiety was higher in FBD patients (77.1%) compared to IBD (47.5%), CC (34.4%) and CG (38.7%), P=0.0003 Depression prevalence was higher in FBD group (60%) compared to the others: CC (40.63%), IBD (24.2%) and CG (21.33%), P<0.0001. Patients had high self-esteem in the majority of cases: CG (96%), IBD (90.9%), CC (93.75%), except in FBD group (61.76%), P<0.0001. There was a high prevalence of Erectile Dysfunction in the sample: FBD (100%), CC (50%), IBD (27.9%) and CG (35.42%) with no difference among groups (P=0.19). The Female Sexual Dysfunction was more prevalent in CC group (100%) compared to the others FBD (66.67%), IBD (46.4%) and CG (33.33%), P<0.0001.
CONCLUSION(S): Patients with FBD had a greater impairment in their quality of life compared to IBD and control groups, as well as a higher prevalence of mood disorders compared to patients with organic diseases and the CG. They also had lower rates of high self-esteem. The female sexual dysfunction was higher in CC compared to the others and no difference in erectile dysfunction rates between the groups was found.
P-079 Young Investigator Effect of Multi-modal Educational Interventions to Improve Healthcare Maintenance of IBD Patients in an Urban Medical Center
Ni Katherine; Rolston Vineet, Dikman Andrew, Liang Peter, Malter Lisa. New York University School of Medicine, New York City, New York
BACKGROUND: Patients with inflammatory bowel disease (IBD) have many unique health maintenance needs and often require therapy necessitating close monitoring. Gastroenterologists often serve as the primary care provider for these patients and therefore must be familiar with the health maintenance needs of IBD patients. In this study, we investigated whether implementing a multi-modal educational intervention could improve providers’ rates of addressing healthcare maintenance measures.
METHODS: A retrospective chart review was performed in 2013-2014 on 208 IBD patients to determine adherence to performance practice measures. From February-April 2016, fellows received a recurring in-service lecture and an IBD clinic note template outlining the 2011 healthcare maintenance recommendations by the American Gastroenterological Association. An iBook was also introduced, which provided a comprehensive overview of IBD practice guidelines. Retrospective chart review was then performed 1 year afterwards. For each patient, performance measures were assessed in both pre- and post- intervention notes in the following categories: vaccinations, bone health, therapy-specific maintenance, tobacco cessation, and cancer screening. Each performance measure was given a score of 0 (not addressed), 1 (addressed), or N/A (irrelevant to subject). The primary outcome was improvement in rates of adherence to performance measures. The adherence rates for pre- and post-intervention groups were compared using a chi-squared test.
RESULTS: A total of 208 pre-intervention clinic visits and 40 post-intervention visits were included for analysis. After the interventions, the rate of healthcare maintenance measures addressed overall increased from 37% to 52% (P<.001) (Figure 1). There were statistically significant improvements in addressing bone health (29% to 63%, P<.001), vaccination (33% to 47%, P<.001), and therapy-specific measures (53% to 74%, P=.01). There were no statistically significant changes in addressing cancer screening (66% to 58%, P=.19) or smoking (23% to 30%, P=.59).
CONCLUSION(S): The use of multiple educational interventions to enhance delivery of IBD healthcare maintenance resulted in improved adherence to healthcare maintenance measures. Targeted educational programs and a multi-modal approach may be an effective method for teaching GI fellows and reinforcing the importance of addressing these measures to optimize the care of their IBD patients.
P-080 Steroids Use Is the Major Factor Associated With Clostridium Difficile Infection During IBD Flares in the Outpatient Setting
Garcia Patrícia1; Chebli Liliana 2, Ribeiro Tarsila3, Castro Antônio Carlos4, Gaburri Pedro3, Pace Fábio3, Barbosa Kátia3, Costa Lívia1, Raimundo Roberta1, Moraes Bernardo1, Assis Isabelle1, Zanini Alexandre1, Chebli Julio5. 1UFJF, Juiz de Fora, Brazil, 2Federal University of Juiz de Fora, Juiz de Fora, Brazil, 3Federal University of Juiz de Fora, Juiz de Fora, Brazil, 4Federal University of Viçosa, Juiz de Fora, Brazil, 5Inflammatory Bowel Diseases Center, Federal University of Juiz de Fora, Juiz de Fora, Brazil
BACKGROUND: The prospective assessment of Clostridium difficile infection (CDI) impact in inflammatory bowel disease (IBD) patients with colitis flare in outpatient setting has far been poorly investigated. We aimed to explore the prevalence and factors associated with CDI in IBD outpatients presenting with colitis flares as well as the outcomes following treatment.
METHODS: In this prospective cohort study, conducted between October, 2013 and July, 2016, 120 IBD patients (55% presenting a colitis flare) and 40 non-IBD controls were assessed for CDI. Multivariate regression was performed to identify predictors of CDI. Outcome analysis was accomplished for recurrent CDI, hospitalization, colectomy, and CDI-associated mortality.
RESULTS: The proportion of patients with CDI was significantly higher in IBD patients experiencing flares than in both inactive IBD and non-IBD groups (28.8% vs. 5.6% vs. 0%, respectively; P=0.001). Females (OR=1.39, 95% CI, 1.13-17.18), younger age (OR=0.77, 95% CI, 0.65-0.92), steroids treatment (OR=7.42, 95% CI, 5.17-40.20), and infliximab therapy (OR=2.97, 95% CI, 1.99-24.63) were independently associated with CDI. There was a dose-related increase in the odds of having CDI on patients using prednisone. All patients treated with vancomycin had a satisfactory response to therapy, but 21% presented recurrent CDI and 16% were hospitalized. Neither colectomy nor mortality was noticed.
CONCLUSION(S): In IBD outpatients presenting with colitis flares, CDI is highly prevalent. Females, younger age, infliximab use, and notably steroids therapy were independently associated with CDI. Most patients with CDI experienced mild-to-moderate disease and prompt treatment with vancomycin was highly effective, what seems to reduce the serious complications risks.
P-081 Body Fluids Composition Estimated by Bioelectrical Impedance in Patients With Inflammatory Bowel Diseases
Batista Gabriela1, Dorna Mariana2; Baima Julio 3, de Barros Jaqueline4, Gondo Fernanda5, Biondi Robertha4, Sassaki Ligia6, Rupp de Paiva Sergio Alberto7. 1UNESP, Botucatu, Brazil, 2Faculty of Medicine of Botucatu, Botucatu, Brazil, 3Faculty of Medicine of Botucatu, Botucatu, Brazil, 4Faculty of Medicine of Botucatu, Botucatu, Brazil, 5 Institute of Biosciences, UNESP / Botucatu., Botucatu, Brazil, 6Unesp- FMB, Botucatu, Brazil, 7Botucatu Medical School, São Paulo State University/UNESP, Botucatu, Brazil
BACKGROUND: Body composition evaluation is necessary to identify nutritional disorders in order to give an adequate response to recovery and/or maintenance of the patient's quality of life and contribute to reduction and prevention of morbidity and mortality. Bioelectrical impedance analysis (BIA) is a safe, non-invasive and easy-to-apply method for assessing body composition. However, its results may change according to the patient's state of hydration. The inflammatory process through the liberation of pro-inflammatory mediators with consequent capillary permeability alteration and interstice liquid extravasation increase the amount of extracellular fluid (ECF), therefore generating edema. The hypothesis of this study was that patients with active inflammatory bowel disease may present an increased percentage of ECF. The aim of this study was to assess the amount of intracellular fluid (ICF) and ECF using BIA and to compare the proportion of these components in patients with inflammatory bowel disease (IBD) in remission and in clinical activity.
METHODS: Patients with Crohn's disease (CD) and ulcerative colitis (UC) were evaluated. The Crohn's Disease Activity Index for CD and the Mayo score for UC were used in addition to the values of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) for classification of disease activity or remission. BIA was performed to determine ICF and ECF and to obtain the ICF/ ECF ratio. Descriptive analyses of the data and t-test or Mann Whitney were performed.
RESULTS: A total of 160 patients were evaluated, of whom 63 had CD and 97 had UC. Twenty-seven patients were identified, 62.96% female, mean age 36.37 (± 14.39) y being 51.85% of them with CD and mean disease duration of 4.04 (± 3.2) y. It was identified 133 (83.12%) patients in clinical remission. Among them, 58.64% were female, mean age was 46 (± 13.4) y, with 36.84% with CD and mean disease duration of 5 (3-8) y. There was significant difference between the time of diagnosis when the two groups were compared (P=0.008), and remission patients had the disease for the longest time. Nevertheless, no difference was observed between ICF (55 (52.8-57.5) vs 55.1 (52.4-57.1), P=0.976) and ECF (45 (42.4-47.1) vs 44.8 (42.5-47.4), P=0.813) in patients in clinical activity and remission, respectively. No difference was observed between the ICF/ECF ratio (1.23(1.12-1.35) vs 1.23 (1.1-1.52), P=0.964) in patients in clinical activity and remission, respectively.
CONCLUSION(S): With these results, it can be concluded that there is no difference between the proportion of these components (ICF and ECF) in patients with inflammatory bowel disease in remission and in clinical activity. Further studies are needed to elucidate this association.
P-082 Rates of Clinical Response, Clinical Remission and Endoscopic Response in Crohn's Disease: Monotherapy Versus Combined Therapy
Moutinho Bruna1; Baima Julio 2, Saad-Hossne Rogerio3, Sassaki Ligia4. 1UNESP, Botucatu, Brazil, 2Faculty of Medicine of Botucatu, Botucatu, Brazil, 3Digestive Surgery Department, Unesp Botucatu, Botucatu, Brazil, 4Unesp- FMB, Botucatu, Brazil
BACKGROUND: Crohn's disease (CD) is a chronic and relapsing condition characterized by an immunological inflammatory reaction in the digestive tract. Its control is essential but it has recently changed, being the mucosa healing the main goal of the current treatment. To achieve it, the use of anti-TNF is sometimes necessary, but mostly, the association with azathioprine has been proven beneficial. The aim of the study was to compare the rates of clinical response, clinical remission, endoscopic response and loss of response among patients with CD treated with monotherapy (anti-TNF) and combined therapy (anti-TNF + azathioprine).
METHODS: A longitudinal, analytical, observational and prospective study of 78 patients with moderate or severe CD with anti-TNF therapy associated or not with azathioprine. Patients were evaluated at weeks 0, 14, 30 and 54. The variables analyzed were: age, gender, disease duration, Montreal classification, CDAI index, hospitalization rates, surgeries and death. Clinical response and remission were defined as drop of at least 70 points in baseline CDAI and CDAI <150 respectively. Endoscopic Response was marked as a decrease of 50% or more compared by the baseline SES-CD. Loss of response was defined as a CDAI worsening in patient with previous clinical response. Statistical Analysis: descriptive and association tests.
RESULTS: The mean age was 28.59 (± 13.42) years, 55% were females and the duration of disease was on average 6.6 (± 5.2) years. Montreal Classification showed commonly L3 (46%), B2 (44%) and B3 (41%) and perianal disease was observed in 50%. Adalimumab was used by 53% and Infliximab by 47%. Clinical response was observed in 80%, of which 88% with ADA and 70% with IFX (P=0.05). Endoscopic response was presented in 74%, 66% in ADA and 84% in IFX group (P=0.07). Adverse event stated in 23% patients presented, infection in 13% and surgery was necessary in 17% of the patients. Most patients used combination therapy (85%). There was no difference in clinical response rates (78% versus 92%, P=0.44), clinical remission (74% versus 92%, P=0.27), endoscopic response (76% versus 67%, P=0,49) and loss of response (20% versus 0, P=0.20) between the combined therapy and monotherapy groups, respectively.
CONCLUSION(S): There was no difference in rates of clinical response, clinical remission, endoscopic response or loss of response between patients treated with anti-TNF therapy isolated and the combination with azathioprine.
P-084 Safety of Short 30 Minutes Infliximab Infusion: A Pilot Study
Damon Alyssa1, Mia Hodges2, Zack Jeremy1, LeStrange Aimee3, Mattar Mark4, Prins Petra5; Charabaty Aline 3. 1Reusch Center, Washington, District of Columbia, 2Reusch Center, Washington, District of Columbia, 3Georgetown University Hospital, Washington, District of Columbia, 4MedStar Georgetown University Hospital, Washington, District of Columbia, 5Georgetown University, Washington, District of Columbia
BACKGROUND: Infliximab (IFX), a TNF-α inhibitor, plays a major role in the treatment of inflammatory bowel disease (IBD). It's typically infused over 2 hours, progressively increasing the infusion rate to a maximum rate of 160ml/hr. This slow infusion was adopted because of concerns for infusion reactions. However, this strategy increases both direct cost (cost per hour of infusion, facility fee, nurse time) and indirect costs (patient time away from work and family). Our pilot study aimed to assess the safety of a shortened 30 min. infusion protocol of IFX.
METHODS: Patients followed at MedStar Georgetown University, who were on a stable maintenance dose of IFX and who had no history of infusion reaction to standard 2hrs IFX infusion were offered to change their infusion time to 30min. We assessed the occurrence of adverse reactions during the infusion and up to 30 days after IFX infusions. Reactions were further classified as drug related or infusion related. We present the data of our 6 months experience with short infusion (i.e. after an average of 3-4 infusions per patient)
RESULTS: Of 121 IBD patients receiving IFX at our institution during the last year, 46 (38%) received 30 min. short infusions and 75 (62%) received standard infusions. Maintenance dose of IFX ranged from 5 mg/kg (69% of patients) to 7.5-10mg/kg (31%). Adverse reactions were reported in a total of 10 patients (8.3%), 4 of which in the short infusion group. A total of 5 patients, 3 of which had short infusion, had drug induced paradoxical psoriasis. Five patients had an infusion reactions: 3 had cardiovascular events (high blood pressure, tachycardia) of which 1 had received a short infusion, and 2 had self limited skin rash. None of these infusion reactions were deemed severe and none lead to a change in the subsequent infusion rate. Correlation studies were performed and no correlation was found between the incidence of adverse events and IFX infusion rate, IFX dose, and duration of IFX therapy before the reaction occurred (n=0.893).
CONCLUSION(S): Short 30 minute IFX infusions in selected patients who are on a stable dose of IFX and have no history of infusion reaction during standard 2hrs infusions were well tolerated and were not associated with an increased incidence of adverse reactions. Further studies on a larger group of patients and for a longer period are needed to confirm these findings. Reduction of infusion time will decrease direct and indirect cost of therapy and improve patient experience.
P-085 Young Investigator Psychiatric Conditions Are Associated With Medical Noncompliance and Worsening Disease Course in IBD Patient Population
Lee Jai Eun, Abboud Rami, Larion Sebastian, McPhail Jim, White Bradley, Sifuentes Humberto. Medical College of Georgia/Augusta University Medical Center, Augusta, Georgia
BACKGROUND: Psychiatric comorbidities such as anxiety and depression are common in patients with IBD and have been shown to decrease medical compliance and quality of life. These conditions can frequently impede the long-term follow up necessary for disease maintenance and IBD remission. Our study investigates whether psychiatric comorbidities in patients with IBD are associated with a worsening disease course in an outpatient GI clinic cohort.
METHODS: A retrospective chart review was performed of patients with IBD who were evaluated in the outpatient GI clinic from 2013-2017. Demographic and medical history including IBD-related factors were compared between patients with and without psychiatric comorbidities (any type) to determine if increasing psychiatric burden was associated with worsening IBD course.
RESULTS: A total of 162 patients were included, of which 48 patients (30%) had a comorbid psychiatric disorder. The mean age was 41.1 years (SD: 16.0), with 62% females, 58% Caucasian, and mean BMI of 26.2 kg/m2. IBD types included 93 patients (57%) with Crohn’s disease and 60 patients (37%) with UC. The most common psychiatric conditions were depression (31) and anxiety (25), of which 36 patients were currently on psychiatric medications. The median age of diagnosis (23.5 vs 24.0 years; P=0.900) or distance from the IBD center (11.4 vs 15.5 miles; P=0.081) were not significantly different between patients with or without psychiatric conditions. However, patients with psychiatric conditions were significantly more likely to have a history of missed GI clinic appointments (94% vs 76%; P=0.044), history of narcotics (34% vs 11%; P=0.008) or illicit drug use (15% vs 0%; P=0.003), and more frequently undergo CT (P=0.154) or MRI (P=0.032) imaging. These patients also had a nonsignificant trend for previous TNF-failure (33% vs 20%; P=0.112) and IBD-related surgery. (52% vs 37%; P=0.104). The use of psychotropic medications, suggestive of more severe psychiatric disease, was associated with increasing narcotic (P=0.006) and illicit drug use (P<0.001) in a dose-dependent manner. Having a psychiatric comorbidity (odds ratio: 4.551; 95% CI: 1.225-16.911; P=0.025) was independently associated with missed GI appointments even after controlling for traditional demographic risk factors such as age, sex, race, insurance status and IBD type.
CONCLUSION(S): Psychiatric comorbidities such as anxiety or depression in patients with IBD are significant risk factors for medical non-compliance and predispose to a worsening disease course. Physicians should emphasize a comprehensive patient-centered approach addressing both physical and mental health when managing the medical needs of patients with IBD.
P-086 Young Investigator Analysis of Factors Associated With Clostridium Difficile Infection Among Hospitalized Patients With Underlying Pouchitis
Kistangari Gaurav 1, Gosai Falgun2, Lopez Rocio3, Shen Bo4. 1University at Buffalo, Buffalo, New York, 2Fairview Hospital, Cleveland Clinic, Cleveland, Ohio, 3Cleveland Clinic Foundation, Cleveland, Ohio, 4Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio
BACKGROUND: Clostridium difficile (C.difficile) infection (CDI) is the leading cause of healthcare associated infections in the United States. Limited data is available on the hospitalized patients with pouchitis with CDI. We sought to evaluate the frequency, risk factors and outcomes of CDI among hospitalized patients with pouchitis.
METHODS: All patients who were admitted to the hospital with an underlying diagnosis of pouchitis at the Cleveland Clinic hospital, Cleveland, between Jan 2013 and Dec 2016, were included in the study. The study protocol was approved by institutional review board at the Cleveland Clinic. Data was obtained by retrospective chart review of the electronic medical records. Univariable analysis was performed to study the risk factors associated with CDI among patients hospitalized with pouchitis. Generalized linear mixed models were used to estimate CDI rates and odds ratios for CDI; models included a random intercept to account for multiple admissions per patient.
RESULTS: A total of 156 subjects with underlying pouchitis were admitted to the hospital from 2013 to 2016. The average age of the patients was 42.3 (±13.9) years and 53% of the patients were males (53%). Around 53% of patients had an admitting diagnosis of pouchitis and 79% of the admissions were related to the pouch. During this period, patients had between 1 and 6 admissions with an average of 1.4 (± 0.89) admissions/patient. A C. difficile test was done for 92 (42%) admissions. Nineteen percent of admissions resulted in a positive C. difficile test. About 25% of females had CDI compared to 15% of males but this did not reach statistical significance (P=0.26). Lower BMI was found to be significantly associated with CDI with a 14% decrease in odds of having CDI for a 1 kg/m2 increase in BMI (OR=0.86; P=0.018). There was no evidence to suggest any other factor is associated with CDI. All subjects remained alive and only 3 were admitted to the ICU who did not have CDI. About 11% of admissions required a readmission within 30 days but all were in non-CDI group.
CONCLUSION(S): CDI among hospitalized patients with pouchitis is not uncommon. Increased awareness and prompt treatment of CDI is essential to improve clinical outcomes.
P-087 Low Incidence of Hepatitis B Seropositivity in Inflammatory Bowel Disease Patients Prior to AntiTNF Therapy
Damon Alyssa1, Mia Hodges2, Zack Jeremy1, Prins Petra3; Charabaty Aline 4. 1Reusch Center, Washington, District of Columbia, 2Reusch Center, Washington, District of Columbia, 3Georgetown University, Washington, District of Columbia, 4Georgetown University Hospital, Washington, District of Columbia
BACKGROUND: Use of anti-TNF in Inflammatory Bowel Disease (IBD) patients with concurrent Hepatitis B Virus (HBV) infection can lead to viral reactivation and potentially fatal liver failure. It is recommended to test HBV serology before starting antiTNF. HBV vaccines have been part of the routine childhood immunization schedule since 1994; 95% of vaccinated immunocompetent individuals will produce protective antibodies, and up to 51% will remain seropositive 30 years after receiving the vaccine. Here we assess the incidence of seropositivity for HBV in IBD patients prior to initiation of antiTNF, and explore potential factors affecting seronegativity.
METHODS: We performed a retrospective analysis of our IBD population at MedStar Georgetown University Hospital who have reported childhood HBV vaccinations. Medical records were mined for relevant demographic, treatment and serology data. We used statistical analysis to determine any correlation between HBV serology and factors such as race, age at diagnosis of IBD, age at HBV serology testing, disease burden (extent of gut involvement, perforating disease), history of prior IBD surgery, and use of immunomodulator.
RESULTS: We identified 200 patients (63% with Crohn's disease and 37% with ulcerative colitis), who adhered to our inclusion criteria. Up to 67% were white, 54.5% were female and 45.5% male. Only 85 patients (42.5%) were seropositive whereas 115 (57.5%) were seronegative for HBV (<10 mlU/mL). The mean age at time of IBD diagnosis was 27.2 years (SD 13.6) and the mean age at HBV serology testing was 36.5 years (SD 13.5), with the median disease duration prior to serology testing of 7 years. Seventy three patients (36.5%) had undergone one or more IBD surgeries, and 33% were on immunomodulator prior to serology testing. Statistical analysis revealed no correlation between HBV seronegativity and race, disease phenotype, age at diagnosis, disease duration prior to serology testing, history of IBD related surgeries, and treatment with immunomodulators (P>0.05). However, there was correlation between seronegativity and high disease burden (P=0.042). Seronegativity also correlated with more advanced patient's age at time of serology testing (P=0.048), with reversal in the ratio of seropositivity:seronegativity after age 30.
CONCLUSION(S): Our IBD cohort had a lower incidence of HBV seropositivity compared to the general population. Furthermore, there was a correlation between HBV seronegativity and higher disease burden. These findings suggest that the disease itself can decrease the immune response or maintenance of response to HBV vaccination. An age of more than 30 years at the time of HBV testing also correlated with seronegativity, which can be explained by a decrease in immunity with time in those vaccinated as infant as seen in the general population, or by the identification of generations of patients who didn't receive vaccination during infancy. More research is required in order to assess the significance between these correlations in larger patient cohorts.
P-088 Conventional Therapy in Adults With Moderate to Severe Inflammatory Bowel Disease: A Systematic Literature Review
Feitosa Flavio 1, Damião Adérson2. 1Departamento Médico, Takeda Distribuidora Ltda, São Paulo, Brazil, 2Medical School, University of São Paulo, São Paulo, Brazil
BACKGROUND: Moderate to severe inflammatory bowel disease (MS-IBD) has a negative impact on patients’ health and quality of life, besides placing a burden on healthcare resources. Control of IBD, including clinical remission and mucosal healing, is important to avoid disease progression. Despite the advent of biological therapy, conventional therapy continues to be used in MS-IBD, especially in countries uninsured for biologicals. This systematic review aims to investigate data on efficacy of conventional therapy for MS-IBD.
METHODS: A systematic review was conducted in June 2017 through Cochrane Collaboration, Medline, and Lilacs databases. Inclusion criteria encompassed meta-analysis, systematic reviews, randomized clinical trials, observational and case-control studies, concerning conventional therapy in adult patients with MS-IBD, including Crohn’s disease (CD) or ulcerative colitis (UC). As conventional therapy, corticosteroids (prednisone, hydrocortisone, budesonide, prednisolone, dexamethasone), 5-ASA derivatives (mesalazine and sulfasalazine) and immunosuppressants (azathioprine, methotrexate (MTX), mycophenolate, cyclosporine, tacrolimus, 6-mercaptopurine) were included. Exclusion criteria were sample size below 50, comparative studies without placebo arm, narrative review, biologic therapy use, and languages other than English, Spanish, French or Portuguese. Outcome measures were clinical remission (induction or maintenance), response and mucosal healing. Two independent reviewers selected eligible studies and extracted data.
RESULTS: 1,988 titles were found and 22 were eligible (8 meta-analysis, 14 individual studies). In meta-analysis, for CD, remission induction or clinical improvement was evaluated for azathioprine and 6-mercaptopurine with no advantage over placebo (risk ratio [RR]: 1.26; 95% confidence interval [CI]: 0.98-1.62). For remission maintenance, budesonide was not effective versus placebo (RR: 1.13; 95%CI: 0.94-1.35 at 12 months follow-up); MTX was superior to placebo (RR: 1.57; 95%CI: 1.10-2.23) with moderate evidence quality; azathioprine or 6-mercaptopurine were superior to placebo in avoiding clinical relapse after surgical treatment (RR: 0.74; 95%CI: 0.58-0.94), with low evidence quality (no other meta-analysis was considered eligible for azathioprine or 6-mercaptopurine in maintenance for moderate to severe CD). For clinical response in UC, meta-analysis showed response rates of 78.0% (95%CI: 71.0–85.0%) and 88.0% (95%CI: 80.0–96.0%) for azathioprine after 6 and 12 months, respectively; and tacrolimus showed higher clinical response versus placebo (RR: 4.61, 95%CI: 2.09–10.17), with durable effect. For remission induction, MTX was not effective versus placebo (RR: 0.96; 95%CI: 0.58-1.59). For remission maintenance, a meta-analysis showed no evidence to support MTX use (RR: 0.64; 95%CI: 0.28-1.45 versus placebo in 36 weeks). For mucosal healing, meta-analysis showed reduction in endoscopic relapse rates for 6-mercaptopurine over placebo in CD (RR: 0.40; 95%CI: 0.19-0.83), and favorable endoscopic remission and mucosal healing rates with azathioprine until 12 months for UC (70%).
Individual studies were mainly for UC, with small sample sizes and short follow up, including cyclosporine, 5-ASA, tacrolimus, corticosteroids, and azathioprine.
CONCLUSION(S): There are not many studies of clinical objective outcomes in MS-IBD, especially for mucosal healing with conventional therapy. As conventional therapies are currently the principal alternative to biologics, robust studies are required to further our understanding of their efficacy since they are the treatments offered to many IBD patients.
P-089 Cardiovascular Risk in Crohn's Disease and Ulcerative Colitis Patients
Biondi Robertha1, Dorna Mariana2; Baima Julio 3, da Silva Rosemary1, Batista Gabriela4, Hueb Joao4, Sassaki Ligia5, Rupp de Paiva Sergio Alberto6. 1Faculty of Medicine of Botucatu, Botucatu, Brazil, 2Faculty of Medicine of Botucatu, Botucatu, Brazil, 3Faculty of Medicine of Botucatu, Botucatu, Brazil, 4UNESP, Botucatu, Brazil, 5Unesp- FMB, Botucatu, Brazil, 6Botucatu Medical School, São Paulo State University/UNESP, Botucatu, Brazil
BACKGROUND: Cardiovascular diseases are the leading cause of mortality worldwide. Recent literature supports an association between inflammatory bowel disease and coronary artery disease. Chronic inflammation, corticosteroid use and increased risk factors such as overweight and obesity contribute to the increased risk of cardiovascular disease in this population. Objective: to evaluate the cardiovascular risk of individuals with Crohn's Disease (CD) and Ulcerative Colitis (UC).
METHODS: A cross-sectional study was conducted with patients with confirmed diagnosis of CD or UC, totalizing a sample of 96 eligible individuals. Fifteen individuals were excluded from the analysis. CD was classified through the Montreal classification and the disease activity through CDAI index. UC was classified according to the extension of the lesion and Mayo Score. The Framingham Risk Score and the presence of atheromatous plaques in the carotid artery evaluated by carotid ultrasonography were used to assess cardiovascular risk. The nutritional evaluation consisted of anthropometry and evaluation of body composition through electrical bioimpedance. The biochemical tests urea, creatinine, homocysteine, total cholesterol and fractions, triglycerides, glycemia and fasting insulin, uric acid, C-reactive protein were used to study chronic inflammation and lipid profile. Statistical analysis: descriptive statistics and association tests (p <0.05).
RESULTS: Eighty-one individuals, 51 (63%) patients with UC (57% pancolitis) and 30 (37%) had CD (L3: 47%, B2: 40%, B3: 40%). The mean age was 48.2 ± 12 y. The majority of the individuals were in clinical remission (59.3%), confirmed by the PCR dosage: 0.7 (0.5-1.6) mg/dl. The median BMI was 26.6 (23.3-30.4) kg/m2 and the body composition assessed by the BIA showed a median lean mass of 49.4 (42-59) and a fat mass of 22.4 (16.1-27.9). Regarding laboratory tests, the results were within the range of normal: homocysteine 9.7 (7.8-12.8) μmol/L; total cholesterol 176.0 (150.0-211.0) mg/dl; HDL cholesterol 48.0 (39.0-59.5) mg/dl, triglycerides 110 (79.5-176.0) mg/dl. According to the Framingham score, 18.8% of subjects presented intermediate or high risk for cardiovascular disease, with no difference between diseases (UC 18.6% vs. DC 19.2%, P=1.0). Presence of atheromatous plaque in the carotid artery was observed in 23.5% of the individuals, with no difference between the diseases (UC 21.2% vs DC 27.7%, P=1.0). Presence of metabolic syndrome was observed in 25.9% of the sample, 27.9% in UC and 36% in CD (P=0.67).
CONCLUSION(S): The cardiovascular risk of patients with IBD is increased according to the Framingham risk score and carotid ultrasound.
P-090 Young Investigator Hypoalbuminemia as Risk Factor for Thromboembolic Events in Hospitalized Inflammatory Bowel Disease Patients: An Observational and Retrospective Analysis
Imbrizi Marcello 1, Lopes Tirzah1, Cunha-Silva Marlone1, Magro Daniela2, Kotze Paulo3, Montes Ciro1, Almeida Jazon1, Cabral Virgínia1. 1University of Campinas, Campinas, Brazil, 2University of Campinas, Campinas, Brazil, 3Colorectal Surgery Unit - Cajuru University Hospital - Catholic University of Parana, Curitiba, Brazil
BACKGROUND: Inflammatory bowel diseases (IBD) are chronic entities characterized by local and systemic inflammation that predominantly affects the gastrointestinal tract and may be associated with numerous extraintestinal manifestations including thrombosis. The association between IBD and thromboembolic events (TEE) was first described in 1936 in a study involving more than 1000 patients with IBD followed at the Mayo Clinic. TEE were found in 1.2% of the cases. Since then, several studies have demonstrated such association. The incidence of TEE in patients with IBD ranges from 1.2-6.7%, increasing to 39% in post mortem. Such events occur mostly at a time when IBD is active and (or) with complications such as stenosis, fistulas and abscesses. The aim of this study was to identify the prevalence of TEE in hospitalized IBD patients and find risk factors for its occurrence.
METHODS: This was a retrospective single-center longitudinal study carried out by reviewing the medical records of patients with IBD from the gastroenterology and colorectal surgery units at the University of Campinas, Brazil, between 2004 and 2014. Patients hospitalized for more than 48 hours, due to active IBD and who did not use prophylaxis for TEE during hospitalization, were included. Patients with hematopoietic systemic diseases or with coagulopathies, using anticoagulant medications up to 30 days before admission and pregnant women were excluded. Patients were allocated in two groups: those with TEE up to 30 days or at the time of hospitalization (TEE-group) and patients without TEE (control-group). Clinical characteristics (disease duration, medical therapy, extra-intestinal manifestations, disease activity) and laboratorial characteristics (complete blood count, CRP, ESR, albumin, pre albumin, coagulogram) of the patients were evaluated.
RESULTS: 45 patients, 23 (51.1%) female were evaluated. 32 patients (71.1%) had Crohn's disease (CD) and 13 (28.9%) ulcerative colitis (UC). At the time of admission, 24.4% of the patients were off treatment due to the recent diagnosis. Only 4.4% of the patients were active smokers and 8.9% were previous smokers. 56.5% of the women used hormonal contraceptive methods. The mean biochemical factors related to the nutritional aspect (albumin and pre-albumin) were reduced (albumin: 3.07±0.94g/dL, pre-albumin: 16.79±10.8mg/dL). Both mean serum albumin and pre-albumin levels were lower in CD (albumin: 2.9±0.93g/dL, pre-albumin: 12.37±8.9mg/dL). The prevalence of TEE, 30 days before or during hospitalization, was 17.7%(n=8), 12.5% in CD and 30.7% in UC. There was no difference between the gender. Patients with TEE presented depletion of the anthropometric status, BMI= 17.6±3.26Kg/m2 in relation to the control group 23.2±3.7Kg/m2. In TEE group, mean serum albumin was 2.06±0.62g/dL vs 3.3±0.85g/dL in the control group. In univariate analysis, only hypoalbuminemia was considered a risk factor for TEE. Individuals with hypoalbuminemia (values below 2.62g/dL) had a 14.8 fold higher chance of developing any TEE (P<0.001).
CONCLUSION(S): TEE were identified in 17.7% of admitted IBD patients. Albumin levels were significantly lower in individuals with TEE. Hypoalbuminemia was a risk factor for the development of TEE in IBD. Serum albumin dosage is a simple and accessible test that can be used in the risk stratification of active IBD patients.
P-091 Causes of Admission in IBD: How Nationwide Trends Have Changed From 2002 to 2007-2012
Htun Zin Mar 1, Gul Muhammad2, Lin Kyawzaw3, Kyaw May4, Shaukat Nauman5, Aye Htar Htar6, Imran Muhammad7, Lwin Aung Khine8. 1Louis A. Weiss Memorial Hospital, Chicago, Illinois, 2Presence St. Joseph Hospital, Chicago, Illinois, 3The Brooklyn Hospital Center, Brooklyn, New York, 4Long Island Jewish Forest Hills Hospital, New York, New York, 5Saint Louis University, St. Louis, Missouri, 6Fayetteville VA Medical Center, Fayetteville, North Carolina, 7Civil Military Hospital, Rawalpindi, Pakistan, 8University of Medicine 1, Yangon, Myanmar
BACKGROUND: Inflammatory bowel diseases (IBD), Crohn’s disease and ulcerative colitis, cause remitting and relapsing episodes throughout their course in patients’ lives. Because of long-standing nature of the disease, various complications of disease become unavoidable and often lead to hospital admission. In this study, we analyzed complications leading to admission from IBD patients and report the top 5 causes.
METHODS: The most common complications leading to admission in IBD in-patients were analyzed using validated International Classification of Diseases, 9th Revision and Clinical Modification (ICD-9M codes) using Nationwide inpatient sample (NIS) from 2002 and 2007-2012. We analyzed 137,212 IBD in-patients from 54,701,220 admissions and top 5 causes with their odds ratios were reported here in addition to nationwide trends.
RESULTS: Intestinal obstruction (IO) without hernia, fluid and electrolyte disorders, other GI disorder, deficiency and other anemia and nutritional deficiencies appeared as most common admission reasons in the order of decreasing frequency. IO without hernia and deficiency and other anemia has been decreasing gradually while nutritional deficiencies and other GI disorders are on the rise. Fluid and electrolyte disorders decreased sharply up to 2009 then started increasing gradually again. Odds ratio (OR) of IBD patients for IO is 26. 84 (P<0. 0001) compared against non-IBD in-patients. OR for fluid and electrolyte disorders are 2. 767 (P<0. 0001), other GI disorders are 7. 76 (P<0. 0001), deficiency and other anemia are 5. 365 (P<0. 0001) and nutritional deficiencies are 4. 778 (P<0. 0001).
CONCLUSION(S): IO without hernia, deficiency and other anemia are well-known as common complications of IBD due to strictures, impaired intake and absorption. Improvement of current treatment regimens addressing these issues can be seen in their decreasing trends. However, despite well-known fact that nutritional deficiencies and other GI disorders are common, their trend is increasing highlights the need to address those issues. Most important of all, fluid and electrolyte disorder, though less aware and reported, stands as second most common cause of admission and trends are on the rise in recent years, indicating the urgent need to address the issue. Our study depicts effectiveness of current treatment guidelines hence aim to help in developing better treatment modules to reduce morbidity of IBD patients.
P-092 Adherence to Quality of Care Indicators is Greater in Inflammatory Bowel Disease Dedicated Gastroenterologists
Thomas Alex 1, Walker Ted2, Gutierrez Alexandra3, Bruns Mark1, Hiatt-Jensen Deborah4, Stenson William1, Deepak Parakkal1, Ciorba Matthew5, Christophi George2. 1Washington University School of Medicine, Saint Louis, Missouri, 2Washington University School of Medicine, St Louis, Missouri, 3Washington University, St. Louis, Missouri, 4Washington University School of Medicine, Creve Coeur, Missouri, 5Washington University in St. Louis, Saint Louis, Missouri
BACKGROUND: Inflammatory bowel disease (IBD) patients often receive inconsistent care that can lead to suboptimal clinical outcomes. Physician performance measures and quality of care indicators for IBD were developed by the American Gastroenterological Association (AGA) and the Crohn’s and Colitis Foundation of America (CCFA) with the goal to improve clinical outcomes, quality of life, and decrease healthcare costs. We aimed to assess adherence to IBD quality care indicators at a tertiary academic center by IBD-dedicated gastroenterologists (IBD-GIs) compared to general gastroenterologists practicing in the referring community that manage IBD patients (Gen-GIs).
METHODS: A prospective review (January 1, 2017 to April 30, 2017) was conducted of consecutive outpatient visits at the gastroenterology clinic at Washington University in Saint Louis. Demographics and established quality of care indicators in IBD as published by AGA and CCFA including in collection were: documentation of IBD phenotype, vaccination status, and appropriate endoscopic evaluation. We compared adherence to quality of care indicators by IBD-GIs managing established IBD patients vs referred patients with IBD managed by community Gen-GIs using t-test, ANOVA (Prism, Irving CA).
RESULTS: Over the study period, 478 patients (median age 42 years, 51% female, 14% African American) were evaluated in the clinic. Disease duration was a median of 14 years, and 55% had Crohn’s disease. 235 patients were managed by IBD-GIs and 248 were managed by Gen-GIs with similar demographics among the two groups. IBD-GIs were significantly more adherent with recommended quality of care indicators compared to Gen-GIs, including IBD phenotype documentation (74% vs 33%, P<0.01), using steroid-sparing treatments to limit corticosteroid usage less than 12 weeks (75% vs 54%, P<0.01), and adherence colon cancer surveillance (62% vs 34%, P<0.01). In addition, regarding health maintenance, IBD-GIs vaccinated more patients compared to Gen-GIs including HBV (76% vs 57%, P=0.02), Influenza (59% vs 40%, P=0.01), and Pneumovax (36% vs 16%, P=0.01).
CONCLUSION(S): IBD-GIs compared to Gen-GIs are consistently and significantly more adherent in the implementation of quality of care indicators for IBD. Our data suggest that patients with IBD might benefit from focused and comprehensive clinical care by IBD-dedicated gastroenterologists and highlights the need for further education of Gen-GI physicians in areas where specialized IBD care is not currently available. Additionally, there are significant areas of improvement in clinical care such as health maintenance, even in IBD dedicated providers.
P-093 Improvement of Disability in Ulcerative Colitis Patients After One Year With Anti-TNF Agents
Bissoli Gabriela1, da Silva Rosemary2; Baima Julio 3, Farinelli Elen2, Síbia Carina2, de Barros Jaqueline2, Biondi Robertha2, Renosto Fernanda2, Saad-Hossne Rogerio4, Sassaki Ligia5. 1UNESP, Botucatu, Brazil, 2Faculty of Medicine of Botucatu, Botucatu, Brazil, 3Faculty of Medicine of Botucatu, Botucatu, Brazil, 4Digestive Surgery Department, Unesp Botucatu, Botucatu, Brazil, 5Unesp- FMB, Botucatu, Brazil
BACKGROUND: Ulcerative Colitis (UC) is an inflammatory bowel disease characterized by a chronic relapsing colon inflammation. The symptoms can have significant psychosocial implications that can affect the health-related quality of life (HRQoL) and cause disability. Anti-TNF agents are not only effective in inducing remission but have also been shown to improve HRQoL. The purpose of the present study was to determine the impact of the treatment with anti-TNF agents on the improvement of quality of life and disability in UC patients.
METHODS: A prospective, longitudinal study was performed on patients with UC treated with anti-TNF agents for one year. Data were collected at baseline prior to initiation of treatment and at weeks 14, 30 and 54 after starting anti-TNF treatment. Biological treatment was indicated for patients with moderate and severe colitis refractory to immunosuppressants, steroids refractory or steroids dependent, and those admitted to the hospital with severe colitis, when they were steroid refractory or dependent. Mayo Score was used to assess the clinical response of UC patients. Clinical response was defined as a reduction of 3 points or more on total Mayo score from baseline. Clinical remission was defined as a total Mayo score of 2 points or lower, with no sub score exceeding 1 point. Endoscopic response was defined as Mayo endoscopic sub score 0 or 1. The inflammatory bowel disease questionnaire (IBDQ) was used to measure the HRQoL at baseline and at weeks 14, 30 and 54. The Karnofsky Performance Scale Index was used to measure disability. The Karnofsky score runs from 100 to 0, where 100 is "perfect" health and 0 is death. Statistical Analysis: variables were analyzed at four time points using variance analysis of repeated measurements (ANOVA) with the Tukey post-test. This study was approved by the Research Ethics Committee (CAAE: 48594815.8.0000.5411).
RESULTS: Thirty patients were included in this study. Sixteen (53.33%) were male, 96.67% Caucasian race, the mean age was 40.47y (±15.87) and the disease duration was 4.80y (± 4.13). Location data included 80% with pancolitis, 20% with left colitis, and no patients with distal colitis. The mean of Mayo score at baseline was 7.63 (±3.12) points and the endoscopy sub score was 2.83 (±0.38) points. Anti-TNF therapy included adalimumab in 8 patients and infliximab in 22 patients. Clinical response was achieved in 22 patients (73.33%) in total; clinical remission was achieved in 15 patients (50%) in total, and the endoscopy response was achieved in 50% of the patients. Patients improved their HRQoL, without differences between groups (P=0.99). The IBDQ score ranges from 118.93 (±46.02) at baseline to 147.52 (±47.21) at week 14 (P=0.11), 164.88 (±48.14) at week 30 (P=0.003) and to 165.13 (±49.24) at week 54 (P=0.004). The Karnofsky score ranges from 68.00 (±17.10) at baseline to 80.00 (±11.74) at week 14 (P=0.003), 84.62 (±10.67) at week 30 (P<0.0001) and to 88.75 (±10.76) at week 54 (P<0.0001).
CONCLUSION(S): UC patients treated with anti-TNF agents presented an improvement in HRQoL and in disability.
P-094 Crohn's Disease and Sarcopenia: Predicting Surgical Outcomes
Shah Marmy1; Ray Jennifer 2, Sontag Stephen1, Hayden Dana3. 1Hines VA Hospital, Hines, Illinois, 2Loyola University Medical Center, Maywood, Illinois, 3Loyola University, Maywood, Illinois
BACKGROUND: Crohn’s disease is often complicated by the formation of fibrosis and strictures which often necessitate bowel resection. Bowel resection is associated with increased mortality, renal, and respiratory failure. Sarcopenia or low skeletal muscle mass is often accelerated in chronic illnesses and has been associated with increased risk of post-surgical complications. The aim of this study is to identify muscle mass as a prognostic indicator for post-operative complications in patients with Crohn’s disease. Our primary analysis includes complications of infection and mortality.
METHODS: We conducted a retrospective study and searched both inpatient and outpatient data of patients with confirmed diagnosis of Crohn’s disease. The search was conducted with ICD-10 codes for Crohn’s, bowel resection, ileocecectomy, and colectomy from January 2000 to January 2017 at Loyola University Medical Center. Sarcopenia was defined using the EWGSOP guidelines using sex-specific skeletal muscle index. Muscle mass was evaluated via analytic morphomics Mimics software measuring cross sectional areas of bilateral psoas and rectus abdominus skeletal muscle on CT abdomen/pelvis or CT enterography at the level of L3 at least 2 months prior to surgical intervention. Pre-operative factors evaluated included hemoglobin, albumin, and CRP while some post-operative complication measures included infection, anastomotic leak, ileus, and death secondary to surgery. Post-operative complications were measured up to 2 years after surgery.
RESULTS: Our search yield 1244 patients; of which, 78 met inclusion and exclusion criteria. Of these 78 patients, 53 were found to have sarcopenia by EWGSOP. In terms or mortality, only 6 of 74 died. Of those 6, only 4 were secondary to immediate post-operative complications. For other secondary outcomes, only 4 patients had anastomotic leaks while 13 had an associated wound infection.
CONCLUSION(S): Sarcopenia was not associated with increased mortality, anastomotic leak, or increased risk of wound infection. This would suggest that although sarcopenia may impact more long-term consequences of Crohns' disease, it is not necessarily a barrier to surgery in patients needed bowel resection.
P-095 Young Investigator Vaccinations in IBD Patients: Internists’ Practice and Perceptions of Responsibility
Hammami Muhammad, Pandit Pratik, Talkin Rebecca, Schroeder Katie. Saint Louis University, Saint Louis, Missouri
BACKGROUND: Inflammatory bowel disease (IBD) patients are at increased risk of vaccination-preventable infections, which is exaggerated by the increasing use of steroids, immune-modulators and biologics. However, it is not clear whether the gastroenterologist (GI) or the primary care provider (PCP) would or should assume responsibility for vaccinations in this population.
METHODS: We anonymously surveyed a convenient sample of 94 internists who are affiliates or trainees of St. Louis University (SLU), St. Louis, Missouri (11.6% university faculty, 5.9% Veterans Administration faculty, 82.5% medical residents), using electronic or paper self-administered instruments.
RESULTS: Out of the 87 participants (response rate 92.5%), 67% (59% alone, and 8% with other specialty) indicated that PP should determine which and when vaccinations should be given (vs. 32% indicating that GI should), 82% that PCP should document and keep track of vaccination status (vs 16% indicating that GI should), and 75% that vaccinations should be ordered by PCP (vs. 23% indicating that GI should). Sixty one percent reported assessing vaccinations all or most of the time (most commonly assessed vaccinations were influenza (93%), pneumococcal PNA (87%), and zoster (64%) and least commonly HPV (21%) and measles/mumps/rubella (29%)), 53% and 17% being comfortable to provide inactivated and live vaccines, respectively, and 23% always providing age appropriate vaccines prior to immune-suppression therapy. When asked about specific clinical scenarios, 18% reported always providing zoster vaccination to patients Ëƒ50 year-old, 8% to patients Ëƒ50 year-old on low dose immune-suppression, and 3% 4 weeks before starting biologics; 0% reported routinely checking varicella IgG titers and providing vaccination accordingly and 2% checking titers and providing vaccination 4 weeks before starting biologics; 69% reported always providing influenza annual vaccination, 67% acknowledged the importance of providing non-live-trivalent vaccine, and 7% reported counseling patients’ households to avoid the inhaled vaccine; and 35% reported always providing pneumococcal vaccinations with PSV23 and 24% providing PSV13 followed by PSV23 ≥8 weeks later and a booster every 5 years to immunosuppressed patients.
CONCLUSION(S): The data indicates a sharp divide in SLU internists’ perception of who should take responsibility of vaccination of IBD patients and that IBD patients’ vaccination is not adequately addressed by internists. The applicability of our results to internists in other settings is not known. We suggest that gastroenterologists maintain full responsibility for vaccination of IBD patients. Alternatively, specific strategies, such as more explicit guidelines for internists and electronic medical record reminders and checkpoints would be required.
P-096 Physical Activity in Daily Life and Exercise Capacity in Patients With Crohn's Disease on Infliximab-Induced Remission: A Cross-Sectional Study
Cabalzar Andrea1, Chebli Liliana2; Ribeiro Tarsila 1, Lucca Fernando3, Gaburri Pedro1, Reboredo Maycon1, Pinheiro Bruno1, Malaguti Carla4, Chebli Julio5. 1Federal University of Juiz de Fora, Juiz de Fora, Brazil, 2Federal University of Juiz de Fora, Juiz de Fora, Brazil, 3Federal University of Juiz de Fora / Gastroenterology Department, Juiz e Fora, Brazil, 4Federal University of São Carlos, Juiz de Fora, Brazil, 5Inflammatory Bowel Diseases Center, Federal University of Juiz de Fora, Juiz de Fora, Brazil
BACKGROUND: Physical activity in daily life and exercise capacity have never been assessed in Crohn’s disease patients on infliximab-induced remission. We aimed to evaluate the physical activity in daily life, exercise capacity, quality of life and mood disorders in patients with moderate-to-severe Crohn’s disease on infliximab-induced remission, and to investigate variables associated with physical activity in daily life in these patients.
METHODS: A cross-sectional study was conducted, in which 26 patients with Crohn’s disease were selected. Controls were currently asymptomatic individuals with functional dyspepsia. Patients underwent to evaluation of physical activity in daily life by a triaxial accelerometer, exercise capacity (shuttle walk test), handgrip strength, quality of life and mood disorders.
RESULTS: The number of steps taken (7446 ± 3081 vs. 7898 ± 2487), the active time (80.6 ± 42 vs. 89.7 ± 24.3 min), the shuttle walk test distance (662.7 ± 252.9 vs. 728.8 ± 346.6 m) and the handgrip (34.3 ± 11.1 kgf vs. 32.9 ± 11.9 kgf) didn’t show significant difference between Crohn’s disease patients and controls, respectively. The time spending lying down (116.3 ± 107.4 vs. 63.7 ± 55.8 min) and some domains of quality of life were superior in Crohn’s disease patients (P<0.05). No correlation was observed between the physical activity in daily life and quality of life or mood disorders in Crohn’s disease patients (P>0.05).
CONCLUSION(S): In conclusion, moderate-severe CD patients on infliximab-induced clinical remission have the same level of physical activity in daily life and exercise capacity when compared with controls. Some domains of QoL were higher in CD patients. However, because asymptomatic patients with quiescent CD can have as low level of physical activity, it is important that strategies to stimulate physical activity be part of the care for CD patients, so that they can to take up and derive optimal benefit from exercise activities.
P-097 Young Investigator Corticosteroid Use Is Not Associated With Decreased Length of Stay in Patients Hospitalized With Crohn’s Associated Small Bowel Obstruction
Quarta Giulio 1, Thanawala Shivani1, Liu Yingheng1, Chang Shannon1, Malter Lisa2, Dikman Andrew3, Hudesman David4. 1NYU School of Medicine, New York, New York, 2NYU School of Medicine, New York, New York, 3New York University School of Medicine, New York, New York, 4New York University School of Medicine, New York, New York
BACKGROUND: Nearly one-half of Crohn’s disease patients require bowel resection within the first 10 years of disease (1). Small bowel obstruction (SBO) is the most common indication for surgery in Crohn’s patients, followed by abscess and presence of fistulizing disease (2). There are little data regarding pharmacologic treatment of Crohn’s-associated SBO with corticosteroids. In particular, the safety and efficacy of corticosteroids in treating inflammation in the setting of acute Crohn’s SBO remains unclear.
METHODS: Our group performed a retrospective chart review of patients admitted with Crohn’s-disease associated SBO to our institution. Key variables examined included use of corticosteroids, length of stay, infectious complications, and short-term requirement for surgery. Inclusion criteria included adults (>18 years) who were not pregnant and carried a known diagnosis of Crohn’s disease. Using the i2b2 search engine, patients admitted with the ICD10 diagnoses for Crohn’s disease and a primary diagnosis of SBO were included. Analysis of outcomes was performed comparing patients who received steroids versus those who did not using t-statistics and chi-square analysis.
RESULTS: Between 2015 and 2017, fifty-seven patients met inclusion criteria. The majority (n=32, 56%) received no corticosteroids for the preceding three months nor during the admission for SBO, while the minority (n=25, 44%) did receive steroids. The mean age of patients (45±19 years vs 46±18 years, P=0.92), and duration of Crohn’s disease (14±13 years vs 14±12 years, P=0.93) did not differ between groups. C-reactive peptide (CRP) on admission did not differ between groups (23.9±17 vs 46.6±78, P=0.49). Eleven patients (19%) required surgery related to Crohn’s disease during or within the three months following admission. There was no difference in requirement for surgery between groups. In multivariable logistic regression, the only factor associated with requirement for surgery was duration of Crohn’s disease (P<0.05). There was no difference in duration of nasogastric tube placement, time to PO challenge, or length of hospital stay. There were no mortalities in either group and no difference in infectious complications after discharge.
CONCLUSION(S): These results suggest that corticosteroids are not associated with improved outcomes in patients with Crohn’s associated SBO. Length of stay is not decreased due to use of corticosteroids. The study is limited by its retrospective design and small sample size. However, future case-control or randomized clinical trials can examine the use of corticosteroids during acute Crohn’s-associated SBO.
1. Frolkis, A. D., Dykeman, J., Negron, M. E., Debruyn, J., Jette, N., Fiest, K. M., Frolkis, T., Barkema, H. W., Rioux, K. P., Panaccione, R., Ghosh, S., Wiebe, S., and Kaplan, G. G. (2013) Risk of surgery for inflammatory bowel diseases has decreased over time: a systematic review and meta-analysis of population-based studies. Gastroenterology 145, 996-1006.
2. Nguyen, G. C., Loftus, E. V., Jr., Hirano, I., Falck-Ytter, Y., Singh, S., Sultan, S., and Committee, A. G. A. I. C. G. (2017) American Gastroenterological Association Institute Guideline on the Management of Crohn's Disease After Surgical Resection. Gastroenterology 152, 271-275.
P-098 Complementary and Alternative Medicine in Brazilian Patients With Inflammatory Bowel Diseases
Henriques Débora1; Baima Julio 2, de Barros Jaqueline3, Vanni Jeslei1, Oliveira Rebeca1, Lima Henrique4, Otiti Jean4, Neves Fabio4, Sassaki Ligia5, Zaltman Cyrla6. 1UNESP, Botucatu, Brazil, 2Faculty of Medicine of Botucatu, Botucatu, Brazil, 3Faculty of Medicine of Botucatu, Botucatu, Brazil, 4UFRJ, Rio de Janeiro, Brazil, 5Unesp- FMB, Botucatu, Brazil, 6Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
BACKGROUND: The conventional treatment of Inflammatory Bowel Disease (IBD) is based on drug therapy, but different studies have shown a progressive increase in the use of Complementary and Alternative Medicine (CAM), usually combined with conventional treatment, which is reported in rates between 31% and 51%. The most commonly used therapies depend on the country of the study. The aim of the study was to evaluate the prevalence of CAM use and the satisfaction with this therapy among IBD patients.
METHODS: A cross-sectional study was performed in adult IBD outpatients with confirmed diagnosis (Crohn's Disease-CD, Ulcerative Colitis-UC), totalizing a sample of 145 eligible individuals. Data were collected from August 2016 to June 2017 in two Southeastern Brazilian reference centers. Sociodemographic variables and medical history were obtained from patient’s medical records. Disease activity was evaluated by Harvey-Bradshaw Index (HBI) and Mayo Score to CD and UC respectively. Disease location and extension was classified through the Montreal classification to both diseases. Questionnaires were employed to evaluate HRQoL (IBDQ), anxiety and depression (HADS) and a semi structured interview was done with a questionnaire that contains the following sections of CAM: 1) CAM products- tea, probiotics, omega 3, homeopathy and herbal therapies. 2) Current or previous use, time duration of use, frequency, indication and patient satisfaction. Statistical analysis: descriptive statistics and association tests (P<0.05). Logistic regression models were performed to study association with clinical variables and CAM use. This study was approved by the Research Ethics Committee (CAAE: 67198117.6.0000.5257).
RESULTS: One hundred and thirty-seven individuals were included, 52.55% were female and the mean age was 40.52y (±14.05). The disease duration was 11.86 y (±7.18); 71 (56.20%) patients had CD and 60 (43.80%) had UC. The majority of the individuals were in clinical remission (CD:67.11%; UC:55.00%) according to HBI and Mayo score. The HRQoL was classified as excellent in 23.53%, good in 47.06%, regular in 22.06% and poor in 7.35% of patients. Sixty one (44.53%) patients presented anxious and 29.93% presented depression according to HADS. Fifteen patients (11%) have used CAM for IBD treatment, such as tea (3.65%), probiotics (5.11%), omega-3 (2.19%), homeopathy (1.46%) and herbal therapies (0.73%). The specific rates of satisfaction for each CAM use were: tea (16.13%), probiotics (23.05%), omega-3 (0), homeopathy (26.67%) and herbal therapies (30%). There was no difference between CAM use in CD patients as compared to UC patients (P=0.40). There was no association between CAM use and clinical variables such as age (OR:1.001; CI95%:0.972-1.030; P=0.96), gender/female (OR:2.393; CI95%:1.0-5.72; P=0.05), IBDQ score (OR:0.995; CI95%:0.985-1.004; P=0.27), HADS anxiety score (OR:1.020; CI95%:0.940-1.107; P=0.63) or HADS depression score (OR:1.034; CI95%:0.943-1.134; P=0.47).
CONCLUSION(S): The prevalence of CAM use was low among Southeastern Brazilian IBD patients. Despite this found, patients were satisfied with this therapy.
P-099 Patient-ly Waiting: A Systematic Review of Patient-Centered Access to IBD Care in Canada
Mathias Holly 1, Veldhuyzen van Zanten Sander2, Kits Olga3, Heisler Courtney1, Jones Jennifer1. 1QEII Health Sciences Centre, Halifax, Canada, 2University of Alberta, Edmonton, Canada, 3Nova Scotia Health Authority/Dalhousie University, Halifax, Canada
BACKGROUND: Inflammatory Bowel Disease (IBD), such as Crohn’s disease and ulcerative colitis, can lead to debilitating lifelong effects on patients’ and their family’s physical, emotional and financial well-being. Canada has the highest prevalence of IBD in the world. Data shows that 1 in 150 Canadians are living with IBD, and 10 200 new cases are diagnosed each year. Access to quality care is critical for disease management. While access to care is typically measured through actual access (e.g. directly measurable dimensions like wait time), increasing emphasis is being placed on perceived access, which is more subjective, but portrays access from a patient-centered perspective. Dimensions of perceived access may include patient knowledge and cultural acceptability of care. A systematic review of the literature was performed to determine how perceived and actual access to specialty care influence disease-related and patient-oriented outcomes for patients living with IBD in Canada.
METHODS: Using a systematic search strategy, Cochrane, PubMed and CINHAL databases were searched for peer-reviewed English language articles published between 2006-2016. Criteria for inclusion were articles which focused on patients living with IBD, and addressed actual and perceived access to IBD specialty healthcare within Canada. Both observational and experimental study designs were eligible for inclusion. Articles were excluded if they did not focus on both IBD and Canada. Study quality was evaluated using the Cochrane risk of bias tool and was assessed by two reviewers. Included articles were analyzed for the following patient focused themes (from the Levesque et al. (2013) patient centered framework): affordability, accessibility, appropriateness, acceptability, availability & accommodation.
RESULTS: The search strategy yielded eight articles based on the inclusion criteria. Of these eight, six addressed perceived access in relation to IBD care, while two focussed on actual access to IBD care. All themes from the Levesque et al. (2013) patient-centered access framework were represented in the literature. Most of the included articles addressed availability and accommodation (e.g. pediatric and late onset service utilization, distance management, wait times, integrated model of care); appropriateness (e.g. distance management, integrated model of care); and affordability of IBD care in Canada (e.g. disease burden, quality of life and support). Only one article addressed approachability and acceptability of IBD care (e.g. patient awareness and advocacy). All included articles emphasized a need for greater patient-centered measures (e.g. multidisciplinary clinics, comprehensive drug plans) with a goal to improve patient access and, ultimately, patient outcomes.
CONCLUSION(S): Canadian-based published research addressing access to IBD care is very limited. This gap constitutes an obstacle to the development of patient centered health care system innovations, such as creating cost-effective patient-oriented improvements in service delivery, which will improve overall patient outcomes. While there are still many unanswered questions concerning the impact of actual and perceived access on IBD patient outcomes, patient-oriented IBD research with a focus on access to specialty care should be a priority.
P-100 Venous Thromboembolism Prophylaxis in Hospitalized Patients With Inflammatory Bowel Disease: Are We Falling Short?
Delmonico Matthew 1, Urbas Ryan2, Huntington William2, Vitorsky Olga2, Canakis Andrew3. 1Lankenau Medical Center, Wynnewood, Pennsylvania, 2Lankenau Medical Center, Wynnewood, Pennsylvania, 3Philadelphia College of Osteopathic Medicine, Wynnewood, Pennsylvania
BACKGROUND: Venous Thromboembolism (VTE) in hospitalized Inflammatory Bowel Disease (IBD) patients increases length of stay by 48% and leads to a 59% increase in hospital charges1. Analyses show30% of gastroenterologists are unaware of ACG guidelines for VTE prophylaxis in hospitalized IBD patients; only 34% reported they would give prophylaxis to patients with an active flare2. We hypothesize that we under-prescribe prophylaxis in IBD patients due to misguided fear of poor outcomes such as bleeding. Our primary objective is to determine if Lankenau Medical Center adheres to guidelines set forth by gastroenterology societies as well as the American College of Chest Physicians in implementing VTE prophylaxis among hospitalized IBD patients.
METHODS: We conducted a retrospective cohort study reviewing inpatient medical records for admissions to Lankenau Medical Center from January 1st, 2009 to December 31st, 2014 with an ICD diagnosis of IBD. Patients were evaluated regardless of admitting diagnosis. Exclusion criteria included age <18 and >90, and patients on long term systemic anticoagulation for any reason, including those with a history of VTE. We subsequently excluded charts from 2009 secondary to a lack of data within the electronic medical record. We collected data on IBD diagnosis (UC vs Crohns), and choice of VTE prophylaxis including enoxaparin, unfractionated heparin, sequential compression devices, Aspirin 81mg BID or none. Additional variables were collected for future analysis. We categorized VTE prophylaxis on admission as follows: a.) Appropriate VTE prophylaxis with heparin or Lovenox; b.) Inappropriate VTE prophylaxis, with sequential compression devices or aspirin; or c.) No VTE prophylaxis.
RESULTS: 568 inpatient charts were evaluated. 182 of these met exclusion criteria; 386 were included. 99% (N=384) had a confirmed diagnosis of Crohn’s disease while 1% (N=4) had Ulcerative Colitis. 49% of patients were placed on appropriate pharmacologic VTE prophylaxis (N= 189). Subcutaneous heparin was implemented in 12% while 37% were started on enoxaparin. The remaining 50% of our population was started on either inappropriate VTE prophylaxis or no prophylaxis at all. Of those started on inappropriate VTE prophylaxis on admission 20% received sequential compression devices while 2% received twice daily aspirin therapy. 27% of our study population was not started on any VTE prophylaxis on admission.
CONCLUSION(S): Appropriate VTE prophylaxis in hospitalized IBD patients has been shown to decrease morbidity, length of stay, and cost. Nevertheless, even experts remain unaware of guideline recommendations for VTE prophylaxis in this population. We showed that our institution is currently falling short of recommendations. Further analysis will determine any significant variables influencing use of VTE prophylaxis in the 50% of our population with inadequate therapy; we hope to define the barriers to VTE prophylaxis initiation, in order to develop a comprehensive intervention to improve our compliance with these guidelines.
P-101 Tolerability of Ustekinumab in Induction and Maintenance for the Treatment of Crohn’s Disease
Loftus, Jr Edward 1, Sattin Bernie2, Jacobstein Douglas3, Gasink Christopher4, Sloan Sheldon5, Feagan Brian6, Colombel Jean-Frederic7. 1Mayo Clinic, Rochester, Minnesota, 2Janssen Inc., Toronto, Canada, 3Janssen Research & Development, LLC, Spring House, Pennsylvania, 4Janssen Research and Development, LLC, Spring House, Pennsylvania, 5Janssen Scientific Affairs, LLC, Horsham, Pennsylvania, 6Robarts Research Institute, University of Western Ontario, London, Canada, 7Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York
BACKGROUND: Tolerance to therapy is critical for patients to receive the maximal treatment benefit. In Phase 3 clinical trials for ustekinumab (UST) for moderate to severe Crohn’s disease (CD), UNITI-1 enrolled anti-TNF failures and UNITI-2 enrolled conventional therapy failures. In UNITI-1, 36.4% had previous intolerance (infusion-related reactions [IRR], delayed hypersensitivity reactions, or injection site reactions [ISR]) that led to discontinuation of the anti-TNF. UNITI-2 enrolled patients that were not intolerant to anti-TNFs, but some were intolerant to immunomodulators (39%) or corticosteroids (15%). Here we assess tolerability as measured by IRR, delayed hypersensitivity, or ISR to UST in the Phase 3 CD trials.
METHODS: All enrolled patients in UNITI-1 and UNITI-2 were given an intravenous (IV) induction infusion of UST 130mg, UST ~6 mg/kg, or placebo (PBO). The IM-UNITI maintenance study began 8 weeks after IV induction; UST IV responders were randomized to UST 90mg SC Q8W, UST 90mg SC Q12W, or PBO. Non-randomized patients, included non-responders to placebo who received 130mg IV UST, then continued to UST 90mg SC Q12W maintenance therapy; non-responders to IV UST who received UST 90 mg SC, then continued UST 90 mg SC Q8W in maintenance; and IV placebo responders who received placebo SC in maintenance.
RESULTS: Overall, IRR were infrequent: 4.0% and 1.9% of all patients in UNITI 1 & 2, respectively, experienced infusion reactions to the single IV dose. There were no differences in IRR between PBO & UST, or between UST doses (UNITI 1 IRRs in 2.0%, PBO and 4.5% UST 130mg and 3.6%, UST ~6 mg/kg; UNITI 2 IRRs in 2.9%, PBO and 2.4% UST 130mg and 1.4%, UST ~6 mg/kg). During IM-UNITI, in non-randomized patients who were non-responders to placebo induction and received a 130mg IV injection, IRR to PBO and UST were similar and infrequent (2.5% and 1.8%, respectively). There were no anaphylactic or delayed hypersensitivity reactions to any IV dose. After SC administration, ISRs were infrequent and not different across groups. In the combined (randomized and non- randomized) population, ISRs were 1.7% with PBO, and 3.0% with UST. No serious ISRs were reported. The most common ISR was erythema, reported in 1.1% of PBO, and 1.7% of UST. There were no anaphylactic or delayed hypersensitivity reactions to any SC dose. Amongst randomized patients, ISRs were infrequent and consistent between groups. ISRs occurred in 3/418 (0.7%) of all UST 90mg Q12W injections and in 12/599 (2.0%) of all UST 90mg Q8W injections. One patient in the entire phase 3 program discontinued therapy due to ISR.
CONCLUSION(S): In a broad population of patients with Crohn’s disease, many of whom were intolerant to previous therapies, UST had a tolerable profile. Rates of IRR and ISR were minimal, and were not different between groups, nor populations.
P-102 Safety of Ustekinumab With and Without Concomitant Corticosteroids or Immunosuppressants in Patients With Moderately-to-Severely Active Crohn’s Disease
Sands Bruce 1, Gasink Christopher2, Jacobstein Douglas3, Ott Elyssa4, Lang Yinghua2, Ramachandran Paraneedharan3, Ghosh Subrata5. 1Icahn School of Medicine at Mount Sinai, New York, New York, 2Janssen Research and Development, LLC, Spring House, Pennsylvania, 3Janssen Research & Development, LLC, Spring House, Pennsylvania, 4Janssen Scientific Affairs, LLC, Spring House, Pennsylvania, 5University of Birmingham, Birmingham, United Kingdom
BACKGROUND: Ustekinumab (UST), a monoclonal antibody to IL-12 and 23, was recently approved for the treatment of moderate-severe CD. Here we report safety data with and without concomitant use of Immunomodulators (IMM) and corticosteroids (CS) in induction and maintenance in patients pooled from the Phase 2 and 3 CD studies.
METHODS: Percentages of patients experiencing safety events (AEs, SAEs, infections, and deaths) were assessed with and without concomitant IMM or CS use at baseline after IV ustekinumab (UST) or placebo (PBO) induction (8 weeks) and were then also compared with SC UST or PBO maintenance (up to 44 weeks) from the Phase 2 and 3 CD clinical studies. Patients who received IV ustekinumab (doses included: 130mg flat dose and 1, 3, 4.5, & 6 mg/kg) during the placebo-controlled induction period (Week 0-8) were pooled from 2 Phase 2 (C0379T07 & CERTIFI) and 2 Phase 3 (UNITI-1 and 2) clinical studies (total n= 1,986). For maintenance, SC UST (combining 90mg q8w and q12w) and PBO were pooled and compared in the randomized responder populations (ie responders to IV ustekinumab induction) from the maintenance phase of the Phase 2 CERTIFI (Week 8 to Week 22) and Phase 3 IM-UNITI (Week 0 to Week 44) studies (total n= 541).
RESULTS: No death occurred in either the induction or maintenance phases in any groups. Through 8 weeks of induction, the percentages of patients with AEs, SAEs, and infections were similar between UST and PBO both on and off IMM and CS: across all 4 subgroups, for UST, 58-63% had AEs, 4-7% had SAEs, and 19-23% had infections and for PBO, 56-66% had AEs, 5-9% had SAEs, and 21-26% had infections. In maintenance, proportions of patients experiencing AEs, SAEs, and infections were generally similar between UST and PBO groups both on and off IMM and CS,: across all 4 subgroups, for UST, 72-82% had AEs, 9-10% had SAEs, and 41-43% had infections and for PBO, 77-87% had AEs, 9-15% had SAEs, and 37-49% had infections. Proportions of patients on CS in both the UST and PBO groups experienced slightly higher rates of AEs compared with those not on CS (UST, 82% vs 74%, respectively; PBO, 87% vs 76%, respectively). Additionally, PBO patients on CS also experienced slightly higher rates of SAEs (15%) and infections (49%) than the other groups (9-12% with SAEs; 37-43% with infections).
CONCLUSION(S): No differences in safety data were identified based on the use of concomitant IMMs or CSs in UST-treated patients with either IV induction or with SC maintenance compared to PBO. The concomitant use of IMM or CS during either IV induction or SC maintenance treatment with UST did not adversely impact the previously reported favorable safety profile of UST in moderate to severe CD patients, although concomitant CS did result in slightly higher rates of events during maintenance, particularly in the PBO group.
P-103 Rapidity of Symptomatic Improvement With Vedolizumab Therapy for Active CD: A GEMINI 2 Post Hoc Analysis
Feagan Brian 1, Lissoos Trevor2, Lasch Karen3, James Alexandra4, Cao Charlie5, Khalid Javaria Mona4, Colombel Jean-Frederic6. 1Robarts Research Institute, University of Western Ontario, London, Canada, 2Takeda Pharmaceuticals USA, Inc., Deerfield, Illinois, 3Takeda Pharmaceuticals USA, Inc., Deerfield, Illinois, 4Takeda Development Centre Europe, Ltd., London, United Kingdom, 5Takeda Pharmaceuticals USA, Inc., Deerfield, Illinois, 6Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York
BACKGROUND: Vedolizumab (VDZ), a humanized monoclonal anti-α4β7 integrin antibody, is approved for the treatment of adults with moderately to severely active Crohn’s disease (CD). Improvements in patient-reported symptoms remain important treatment goals for patients. We aimed to characterize the rapidity of symptomatic improvement following VDZ induction therapy in the GEMINI 2 trial.
METHODS: Patients with active, moderate to severe CD were randomized to receive placebo (PBO) or VDZ at weeks (wks) 0 and 2 during the 6-wk induction phase. The two patient-reported components of the Crohn’s disease activity index (CDAI) score—abdominal pain subscores (APS) and number of liquid or very soft stools subscore, or stool frequency (SF)—were evaluated at 0, 2, 4, and 6 wks. Mean percentage change from baseline was reported for the overall population and in patients who were tumor necrosis factor antagonist (TNF) naïve. The difference in adjusted percentage change from BL between VDZ and PBO was determined using an ANCOVA model with treatment as a factor and baseline values as covariates.
RESULTS: The adjusted treatment difference in abdominal pain score (APS) (%) with 95%CI for Weeks 2, 4, and 6 were -19.4 (-32.2, -6.6), -22.0 (-33.7, -10.2), and -21.1(-33.1, -9.1) respectively for TNF naïve patients and -10.4 (-18.1, -2.7), -11.2 (-18.9, -3.5) and -11.7(-19.9, -3.6) respectively for all patients. Similarly, greater percentage decreases in SF were observed with VDZ than with PBO, reaching statistical significance at wks 2 and 6. The adjusted treatment difference (%) with 95%CI for Weeks 2 and 6 were -14.5 (-23.3, -5.6) and -16.4 (-28.7, -4.0) respectively for TNF naïve patients and -9.3(-16.2, -2.4) and -11.5 (-20.0, -3.0) respectively for all patients, which was statistically significant. A composite score of APS and SF showed similar trends with significantly greater percentage decreases with VDZ than PBO at all time points. The adjusted treatment difference (%) with 95%CI for Weeks 2 and 6 were -14.6 (-23.1, -6.0) and -14.8 (-25.9, -3.7) respectively for TNF naïve patients and 8.2 (-14.1, -2.4) and -9.4 (-16.8, -2.0) respectively for all patients. Overall, for APS and SF endpoints, the differences in percentage change between VDZ and PBO were greater in naïve pts than in the overall population. Notably, differences in percentage APS decrease from BL in naïve pts were about 2- times as much as in the overall population [% decrease in naïve vs overall: -19.4 vs -10.4; -22.0 vs -11.2; -21.1 vs -11.7 at wks 2, 4, and 6, respectively].
CONCLUSION(S): Symptomatic improvements were achieved with VDZ therapy as early as wk 2, with greater differences from PBO observed in TNF-naïve patients compared with the overall population. These results highlight that rapid onset of action of VDZ in CD occurs within a 6 week induction period; however, maximum efficacy may require assessment at week 14 as per prescribing information.
P-104 Vedolizumab Demonstrates Early Symptomatic Improvement in Ulcerative Colitis: A GEMINI 1 Post Hoc Analysis
Feagan Brian 1, Lasch Karen2, Khalid Javaria Mona3, Cao Charlie4, Wojtowicz Abigail5, James Alexandra3, Colombel Jean-Frederic6. 1Robarts Research Institute, University of Western Ontario, London, Canada, 2Takeda Pharmaceuticals USA, Inc., Deerfield, Illinois, 3Takeda Development Centre Europe, Ltd., London, United Kingdom, 4Takeda Pharmaceuticals USA, Inc., Deerfield, Illinois, 5Takeda Pharmaceuticals USA, Inc., Deerfield, Illinois, 6Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York
BACKGROUND: Vedolizumab (VDZ) achieves long term clinical remission and mucosal healing in patients (pts) with moderately-to-severely active ulcerative colitis (UC). Relief of rectal bleeding (RB) and stool frequency (SF) remain important treatment goals for pts and key indicators of remission for physicians. We aimed to characterize early symptomatic response with VDZ, specifically evaluating the timing of RB and SF improvement.
METHODS: We assessed symptomatic improvement with VDZ through post-hoc analysis of GEMINI 1 data. Pts with active, moderate-to-severe UC were randomized to receive double-blind placebo (PBO) or VDZ at weeks (wks) 0 and 2 during the 6-wk induction phase. Mayo clinic SF subscores (SFS) and RB subscore (RBS) were evaluated at 0, 2, 4, and 6 wks. Mean subscores and mean percent change from baseline (BL) were reported for the overall population and in those who were tumor necrosis factor antagonist (anti-TNF) naïve. The percentages of pts who reached SFS≤1 and/or RBS=0 were also determined.
RESULTS: In anti-TNF-naïve pts, greater percentage decreases in mean SFS from BL were observed with VDZ vs PBO, reaching statistical significance at wks 4 and 6 as suggested by the non-overlapping 95% confidence intervals. Percent change from baseline (95%CI) at wks 2, 4, and 6 were -19.9(-28.0, -11.8), -35.7(-45.2, -26.2) and -36.5(-45.0, -28.0) respectively for VDZ and -5.0(-15.7, 5.7), -0.4(-12.8, 11.9) and -12(-23.4, -0.6) respectively for PBO. The same trends were observed in the overall population without reaching statistical significance. Percent change from baseline (95%CI) at wks 2, 4, and 6 were -12.3(-18.6, -6.0), -23.5(-31.2, -15.7) and -25.0(-31.6, -18.3) respectively for VDZ and -6.4(-14.2, 1.5), -9.9(-19.5, -0.3), and -12.4(-20.8, -4.0) respectively for PBO. Similarly, a numerically greater percentage decrease from BL in RBS was observed with VDZ vs PBO, reaching statistical significance at wk 6 in both anti-TNF-naïve and overall populations. Percent change from baseline (95%CI) at wks 2, 4, and 6 for anti-TNF-naïve pts were -29.8(-39.2, -20.4), -45.6(-55.4, -35.9) and -59.0(-67.6, -50.3) respectively for VDZ, and -19.8 (-32.3, -7.3), -28.0(-40.8, -15.3) and -27.1(-38.7, -15.4) respectively for PBO. Percent change from baseline (95%CI) at wks 2, 4, and 6 for overall pts were -28.6 (-35.5, -21.6), -42.3(-49.5, -35.1) and -49.5 (-57.0, -41.9) respectively for VDZ and -20.7 (-29.4, -12.1), -29.6(-38.4, -20.7) and -26.8 (-36.3, -17.3) respectively for PBO. Significantly higher percentages of pts achieved SFS≤1 or RBS=0 with VDZ vs PBO at wk 6 (32% higher with 95%CI:19.5-44.6 and 22.9% higher with 95%CI:9.8-36.0, respectively) and as early as wk 2 (22.2% higher with 95%CI of 9.6-34.9 and 12.3% higher with 95%CI:0.6-24.1, respectively) among the anti-TNF-naïve population. A composite of SFS≤1 and RBS=0 was achieved in a significantly greater percentage of pts with VDZ than PBO at all time points for both anti-TNF naïve and overall populations with treatment differences of 15.7% and 9.0% at Week 2.
CONCLUSION(S): Symptomatic improvements were achieved with VDZ as early as wk 2, with greater differences from PBO observed in anti-TNF-naïve pts. These results highlight the rapid onset of VDZ in UC; however, assessing efficacy at wk 14 and beyond for those who exhibit a more gradual response should be used to inform clinical practice.
P-105 Etrolizumab Treatment Improves Histologic Activity as Assessed by Both the Robarts Histopathology and Nancy Histological Indices
Peyrin-Biroulet Laurent1, Feagan Brian2, De Hertogh Gert3, Rubin David T.4, Maciuca Romeo5, McBride Jacqueline5; Arulmani Udayasankar 5, Scherl Alexis5. 1Gastroenterology Unit, Nancy, France, 2University of Western Ontario, London, Canada, 3University of Leuven, Leuven, Belgium, 4University of Chicago Medicine, Chicago, Illinois, 5Genentech, Inc., South San Francisco, California
BACKGROUND: Etrolizumab, an anti-β7 monoclonal antibody, showed efficacy and safety during 10 weeks of induction in patients with moderate-to-severe ulcerative colitis in the Phase 2 EUCALYPTUS trial. Since a reduction in histologic inflammation has been linked with improved long-term clinical outcome, and the FDA recommends using both histologic and endoscopic assessments for efficacy evaluation, the effect of etrolizumab on histologic inflammation was evaluated in mucosal biopsies from EUCALYPTUS patients using the Robarts histopathology index (RHI) and Nancy histological index (NHI).
METHODS: 124 patients were randomly assigned (1:1:1) to receive subcutaneous etrolizumab (100 mg at weeks 0, 4, and 8, with placebo at week 2, or 420 mg loading dose at week 0, followed by 300 mg at weeks 2, 4, and 8) or matching placebo. Biopsies were taken using flexible sigmoidoscopy/full colonoscopy from the most inflamed colonic area within 10-40 cm from the anal verge at baseline and at week 10. 62 patients provided consent for long-term sample storage for research; batched H&E-stained slides were scored by a single pathologist using the Geboes scale (later converted to RHI) and NHI. At week 10, mean changes in RHI and NHI scores for pooled etrolizumab or placebo were calculated. Subanalyses explored histologic response (reductions of ≥ 6 or 10 points or ≥ 50% improvement from baseline RHI and ≥ 1 or 2 points reduction from baseline NHI), remission (no neutrophils, RHI ≤ 4 and NHI=0, ≤ 1 or 2) and correlation with endoscopic improvement.
RESULTS: Analysis included 56 patients with baseline data and baseline NHI>1. At week 10, RHI and NHI scores decreased by a greater extent with etrolizumab compared with placebo, regardless of anti–tumor necrosis factor α (aTNF) experience (RHI −8.4 vs −1.6; P=0.032 and NHI −1.2 vs −0.2; P=0.011 for all comers). A greater proportion of etrolizumab-treated patients achieved categorical histologic improvement and remission; specifically, histologic improvement was achieved in 49% (≥ 6 decrease from baseline RHI) and 58% (≥ 1 decrease from baseline NHI) of patients receiving etrolizumab compared with 30% and 14% receiving placebo, respectively. Of patients with an endoscopic subscore (ES) ≤ 1 at week 10 (n=6), 100% experienced histologic response as assessed by RHI (5/5 with RHI nonmissing at week 10), and 83% (5/6) by NHI. Mean (SD) RHI changes were −19.2 (10.0) in patients with an ES ≤ 1 at week 10 versus −4.4 (10.1) in patients with an ES>1. Mean (SD) NHI changes were −2.5 (1.5) in patients with an ES ≤ 1 at week 10 versus −0.6 (1.3) in patients with an ES>1. Spearman correlation coefficients between RHI and NHI were 0.82 at baseline and 0.91 at week 10, while both histologic scores were similarly correlated with ES (0.25-0.28 at baseline and 0.38-0.40 at week 10).
CONCLUSION(S): Histologic activity assessment using RHI or NHI demonstrates improvement after week 10 with etrolizumab treatment and was greater in aTNF-naive patients. Importantly, RHI or NHI reductions were associated with improved ES at week 10.
P-106 Long, Non-coding RNA Gene Expression Signatures to Distinguish Irritable Bowel Syndrome and Inflammatory Bowel Disease
Spurlock, III Charles 1, Tossberg John2, Shaginurova Guzel1, Harmata Andrew2, Crooke, III Philip3, Aune Thomas4. 1IQuity, Inc./Vanderbilt University School of Medicine, Nashville, Tennessee, 2IQuity, Inc., Nashville, Tennessee, 3IQuity, Inc./Vanderbilt University, Nashville, Tennessee, 4IQuity, Inc./Vanderbilt University School of Medicine, Nashville, Tennessee
BACKGROUND: lncRNAs play critical roles in the regulation gene activity. This extends to genes whose protein products are critical for mounting both innate and adaptive immune responses. Our understanding of the functional role of lncRNAs in human diseases, including gastrointestinal disease, is in its infancy. No blood-based RNA biomarkers have been made commercially available to distinguish IBS from IBD or identify individual inflammatory colitides. Here we sought to develop machine learning classifiers using long, non-coding RNA (lncRNA) gene expression data from blood to distinguish irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD).
METHODS: Peripheral whole blood collected into PAXgene tubes was obtained from healthy control subjects (n=115), and patients diagnosed with irritable bowel syndrome (n=128), Crohn’s disease (n=89), and ulcerative colitis (n=84). Patients diagnosed with celiac disease (n=39) were recruited as an additional inflammatory disease control group for classifiers capable of distinguishing IBS from Crohn’s disease or ulcerative colitis. RNA sequencing was performed using a small subset of healthy control, celiac, Crohn’s disease and ulcerative colitis patient samples to derive 48 highly differentially expressed candidate lncRNA gene targets. To validate sequencing findings, RT-PCR was performed on all patients recruited in the study (n=489). Gene expression datasets generated were used to train and independently validate machine learning classifiers capable of distinguishing IBS and IBD from other subjects in the study cohort.
RESULTS: lncRNAs measured by RT-PCR exhibit high degrees of differential expression across healthy control, IBS, and IBD cohorts. Unlike previous studies of mRNAs, lncRNA expression differences were frequently 4-fold or greater in case/control comparisons. lncRNAs exhibit a high degree of discriminatory power and confidence of machine learning predictions with accuracy exceeding 90% for classifiers capable of discriminating irritable bowel syndrome from other inflammatory conditions and healthy controls.
CONCLUSION(S): Gene expression data derived from peripheral whole blood analyzed using machine learning methods produces classifiers capable of distinguishing presence of irritable bowel syndrome and inflammatory bowel disease. Use of this information may provide clinically actionable information for healthcare providers.
P-107 Efficacy of Quantitated Autofluorescence Imaging Endoscopy in Patients With Ulcerative Colitis: A Multicenter Study
Moriichi Kentaro 1, Fujiya Mikihiro1, Sugiyama Yuya1, Iwama Takuya1, Ijiri Masami1, Tanaka Kazuyuki1, Takahashi Keitaro1, Sakatani Aki1, Ando Katsuyoshi1, Nomura Yoshiki1, Ueno Nobuhiro1, Kashima Shin1, Inaba Yuhei2, Ito Takahiro3, Okumura Toshikatsu1. 1Asahikawa Medical University, Asahikawa, Japan, 2Asahikawa City Hospital, Asahikawa, Japan, 3Asahikawa Kousei Hospital, Asahikawa, Japan
BACKGROUND: The evaluation of mucosal inflammation by endoscopy is crucial to determine the therapeutic strategy in patients with ulcerative colitis. The Mayo endoscopic score (Mayo-ES) or Matts endoscopic score (Matts-ES) and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) have generally been used for endoscopic assessments. Image-enhanced endoscopy, including autofluorescence imaging (AFI), is also applied clinically. It is crucial to understand the characteristics of each endoscopic assessment. The aim of this study was to evaluate these endoscopic assessments in UC patients.
METHODS: One hundred and thirty-three patients diagnosed with UC who underwent white light endoscopy (WLE) and AFI at Asahikawa Medical University Hospital between 2007 and 2015 were enrolled in this study. A total of 300 endoscopic images were assessed using the Mayo-ES, Matts-ES, UCEIS and quantified AFI by 5 experts (ex-group) and 5 residents (non-ex-group) in 3 different hospitals. A lesion was categorized as endoscopically active when the Mayo-ES or Matts-ES was 2 or more. AFI images were quantified using an image-analysis software program. The ratio of the reverse gamma value of green (fluorescence) divided by that of red (reflex) was defined as the fluorescence index (F-index). Biopsy specimens were obtained from all lesions corresponding to the images and evaluated according to Matts pathological criteria. We retrospectively investigated 1) the cut-off value of F-index using a receiver operating curve (ROC) analysis, 2) the diagnostic accuracy for mucosal inflammation and the kappa value for the inter-observer agreement of each endoscopic assessment in ex-group and non-ex-group and 3) the additional efficacy of the F-index for improving the Mayo-ES.
RESULTS: 1) The ROC analysis showed that the optimum cut-off value for the F-index for active inflammation was 1.00. 2) The accuracy/kappa value of the Mayo-ES, Matts-ES, UCEIS and F-index for active inflammation were 73.5%/0.62, 78.1%/0.78, 80.9%/0.85 and 75.5%/0.96 in the ex-group, respectively, and 71.1%/0.52, 77.4%/0.66, 76.0%/0.71 and 75.8%/0.99 in the non-ex-group, respectively. The UCEIS showed a significantly high accuracy in ex-group in comparison to other assessments, but no significant difference in the non-ex-group in comparison to other assessments. The F-index showed an excellent kappa value in both group. 3) The average accuracy of each Mayo-ES score in the ex-group versus the non-ex-group was as follows: 0, 88.5% vs. 77.7%; 1, 39.2% vs. 48.2%; 2, 92.0% vs. 81.0%; and 3, 97.1% vs. 89.1%, respectively. The F-index significantly increased the diagnostic accuracy in lesions classified into Mayo-ES 1 from 39.2% to 67.8% in the ex-group and 48.2% to 65.4% in the non-ex-group.
CONCLUSION(S): The diagnostic accuracy of UCEIS for inflammation activity was significantly higher among experienced endoscopists than non-experienced endoscopists. The quantified AFI (F-index) showed an excellent kappa value with sufficient diagnostic accuracy, regardless of the endoscopic experience, and was thus considered useful for estimating the UC activity, especially for non-experienced endoscopists.
P-108 Therapeutic Drug Monitoring of the Biosimilar SB2 (RENFLEXIS™, Infliximab-abda) Using LabCorp Infliximab Assays for Drug Level and Anti-drug Antibodies
Chun Kelly 1, Garcia Gonzalez Zonia2, Yang Jane1. 1LabCorp, Calabasas, California, 2LabCorp, Calabasas, California
BACKGROUND: Therapeutic drug monitoring (TDM) of infliximab (IFX) concentration and anti-infliximab antibody (ADA) titer has helped physicians make informed clinical decisions in the management of inflammatory bowel disease (IBD). A TDM-based approach to treating IBD patients has been used to improve clinical efficacy of anti-TNF agents. The LabCorp IFX TDM test (drug and ADA levels) has been validated in peer-reviewed literature and is widely used by clinicians to help maximize treatment response. Recently approved by the FDA for treatment of IBD, RENFLEXIS (SB2, infliximab-abda) is a biosimilar of the originator infliximab (TNF alpha inhibitor). The aim of this study was to validate the LabCorp IFX TDM test for the quantification of serum SB2 concentrations and ADA.
METHODS: To demonstrate ability to measure RENFLEXIS using the LabCorp IFX TDM test, SB2-specific immunoassays were developed. SB2 calibrators and SB2-conjugated key reagents were used to compare with IFX TDM kits. Analytical performance including accuracy, precision, spike and recovery, specificity and selectivity was assessed. Exogenous SB2 was spiked into donor serum to assess recovery using the IFX drug assay. 124 IFX-treated IBD patients were split-tested using SB2 and IFX drug and ADA assays to assess equivalency and interchangeability between the two methods.
RESULTS: Both SB2 drug level and ADA showed excellent agreement to IFX drug level and ADA respectively. SB2 assay accuracy (<11% bias) and precision (<7% CV) were equivalent to IFX accuracy (<5% bias) and precision (<10% CV) across the measuring range of the assay. More importantly, spike and recovery of RENFLEXIS using the IFX drug assay was equivalent to the recovery of reference product IFX using the IFX drug assay. SB2 was spiked into the donor serum pool to generate 0.25, 0.5, 1.0, 2.0, 4.0, 5.0, 6.0, & 8.0 ug/mL targets. The same target concentrations were generated for IFX. Both sets of targets were read using the IFX drug assay. Percent recovery of SB2 ranged from 87% to 114%; IFX recovery was 83% to 113%. Average spike and recovery was 99% for both SB2 and IFX using the IFX drug assay. Both the SB2 drug assay and IFX drug assay were used to analyze 59 serum samples of IBD patients treated with reference product IFX. The calculated linear regression between the two methods was Y=1.11x-0.13 and r2=1.0. The SB2-specific anti-drug antibody assay performed essentially identically to the reference product IFX ADA assay in terms of precision (<10% CV), accuracy (<10% bias), linearity, drug tolerance and sensitivity. 65 ADA positive serum samples from IBD patients were tested using the SB2 ADA assay. Antibody titer values were compared. Linear regressions of Y=1.09x-8.7, r2=0.99 were obtained.
CONCLUSION(S): This study demonstrates complete cross-reactivity of RENFLEXIS (infliximab-abda) in LabCorp IFX TDM assay. Healthcare providers can confidently use LabCorp IFX TDM test to monitor RENFLEXIS (infliximab-abda) serum drug levels and ADA titers in their patients.
P-109 Use of Therapeutic Drug Monitoring (TDM) to Aid Treatment Decision Making: A Retrospective View From a Large Community Practice
Fourment Chris, Pieper Alexander, Ritter Tim. Texas Digestive Disease Consultants, Southlake, Texas
BACKGROUND: Traditionally, when a patient’s inflammatory bowel disease (IBD) symptomology worsens, physicians make a decision to either change the current therapy based on perceived loss of response or continue on the same therapy, adjusting either dose or frequency. Consequently, many patients are discontinued from effective therapies too soon, while others remain on ineffective therapies in the hopes that the clinical outcome will eventually improve. We aimed to provide insight into the usefulness of therapeutic drug monitoring (TDM) in a large community practice.
METHODS: We conducted a retrospective analysis of patients receiving Infliximab (IFX) infusions who had TDM assays drawn between August 1st, 2016 and July 31st, 2017. We documented serum IFX and antibody to Infliximab (ATI) levels, alongside 4 categories of lab values (C-reactive protein, sedimentation rate, albumin, fecal calprotectin) and 3 categories of patient clinical symptoms (bowel movements, abdominal pain, rectal bleeding) to measure overall patient symptomology. We then examined the physician response to TDM and the impact it had on patient symptoms and lab values.
RESULTS: A total of 67 IBD patients received a serum IFX level result lower than 4 μg/mL (34 Male, 43 CD). 23 patients had an undetectable serum IFX level (34.3%), 50 patients had an undetectable ATI level (74.6%) while 10 patients had an ATI level greater than 200 ng/mL (14.9%), and 7 patients had an undetectable level of both serum IFX and ATI (10.4%). 17 patients changed therapy following the TDM results (25.4%), with 3 patients (17.6%) changing therapy more than once. 24 patients changed the dosage and/or frequency of Remicade infusions (35.8%), with 1 being taken off therapy altogether. 26 of the 67 patients (38.8%) had no change in therapy despite low or undetectable drug levels.
CONCLUSION(S): Therapeutic Drug Monitoring led to more appropriate management of drug therapy in a majority of patients. However, in many patients the information received was not optimally interpreted or utilized. This suggests that further physician education or possibly automatic drug management protocols are needed to optimize patient outcomes.
P-110 Diagnostic Performance of Zinc Protoporphyrin/Heme Ratio in Screening of Anemia and Non-anemic Iron Deficiency in Patients With Inflammatory Bowel Disease
Aksan Ayşegìl1, Leventi Lena2, Radeke Heinfried3, Dignass Axel4; Stein Jìrgen 5. 1Hacettepe University, Ankara, Turkey, 2DGD Clinics Sachsenhausen, Frankfurt/Main, Germany, 3Goethe University Frankfurt, Frankfurt/Main, Germany, 4Agaplesion Markus Krankenhaus, Frankfurt, Frankfurt/Main, Germany, 5Interdisciplinary Crohn Colitis Centre Rhein-Main, Frankfurt/Main, Germany
BACKGROUND: Anemia in inflammatory bowel disease (IBD) is related to the chronic inflammatory nature of the disease and is commonly associated with iron deficiency (ID). However, the diagnosis of iron deficiency by means of currently available laboratory parameters is hampered by the lack of a gold standard and is even more complex and nonspecific in the presence of concomitant inflammatory conditions. Ferritin, in particular, as an acute-phase protein, may be strongly influenced by active inflammation. Zinc protoporphyrin (ZPP) has been identified as a promising screening method for iron deficiency, even in the presence of inflammation. Increase in ZPP/heme ratio has been demonstrated to correlate well with other parameters of iron homeostasis. The aim of this study is to investigate and compare the diagnostic performance of ZPP in ID, iron deficiency anemia (IDA), anemia of chronic disease (ACD) and combined ACD/IDA.
METHODS: The study population consisted of 130 patients with IBD (62.5% female) who consecutively attended the Crohn-Colitis Center Frankfurt for routine evaluation between May 2008 and December 2013. Blood count, transferrin saturation (TSAT), serum ferritin (SF), C-reactive protein (CRP), and zinc protoporphyrin (ZPP) were determined by routine assays. Anemia was defined according to the World Health Organization criteria, as a hemoglobin concentration of <13g/dL for men and <12g/dL for women. For the multiple-criteria model, ID was considered present if individuals had ≥2 abnormal values from among ferritin (<30μg/L), TSAT (<20%), and ZPP (<40μmol/mol Hb). Patients with anemia were classified as having IDA if active inflammation was absent (CRP ≤5mg/L) and TSAT<20% and ferritin level <30μg/L. Patients were classified as having ACD if active inflammation (CRP >5mg/L) was present and TSAT <20% and ferritin ≥100μg/L. Mixed anemia, IDA/ACD, was defined as active inflammation (CRP >5mg/L) and TSAT <20% and ferritin level <100μg/L.
RESULTS: ZPP showed a better correlation with haemoglobin values than either ferritin or TSAT (correlation coefficients; -0.471, 0.376, 0.469 for ZPP, ferritin and TSAT, respectively; P<0.001). On the other hand, no correlation was found between ZPP and CRP (correlation coefficient; -0.097, P>0.05). The receiver operating characteristic (ROC) curves for the various iron indicators used to diagnose any type of anemia as defined by the multiple-criteria model indicated that the diagnostic accuracy of ZPP was superior to that of either ferritin or TSAT (AUC; 0.667, 0.380, 0.327 for ZPP, ferritin and TSAT, respectively).
CONCLUSION(S): Determination of ZPP allows detection and quantification of impaired iron homeostasis in patients with chronic inflammatory disorders. Our results clearly demonstrate the potential utility of ZPP for detection of iron deficiency in IBD patients with inflammation and anemia. Furthermore, our findings indicate that ZPP is a more reliable marker of iron deficiency than either ferritin or TSAT in patients with inflammatory disease, regardless of the degree of inflammation and the presence of anemia. Therefore, ZPP presents a useful additional diagnostic tool in screening for anemic and non-anemic iron deficiency in IBD patients.
P-111 Young Investigator Vedolizumab Trough Levels in Inflammatory Bowel Disease: Initial Clinical Experience
Al-Bawardy Badr, Piovezani Ramos Guilherme, Loftus, Jr Edward. Mayo Clinic, Rochester, Minnesota
BACKGROUND: Therapeutic drug monitoring is an integral part of inflammatory bowel disease (IBD) management. Vedolizumab trough level evaluation has recently become available, but the clinical utility and optimal cutoff value of these levels have not been well defined. The aims of this study are to determine: 1) the median vedolizumab trough level and frequency of detectable antibodies; 2) the effect of concomitant corticosteroids and combination immunomodulator therapy on vedolizumab trough level; 3) the correlation of vedolizumab tough levels with C-reactive protein (CRP) and mucosal healing (MH); and 4) change in clinical management based on vedolizumab trough levels.
METHODS: A retrospective study of IBD patients treated with vedolizumab from January 1st 2008 to March 1st 2017 at our institution was conducted. Patients who have had vedolizumab trough levels checked were included in the study. Data were abstracted for demographics, smoking status, and IBD disease and management details. Endoscopic and CRP data were collected if they were performed within 3 months and 30 days of vedolizumab trough level, respectively. Outcomes included: median vedolizumab level in the cohort; presence of anti-vedolizumab antibodies; effect of corticosteroids and concomitant immunomodulator therapy on vedolizumab levels; and median vedolizumab level associated with normal CRP (< 3 mg/dL) and MH.
RESULTS: A total of 50 patients (68% CD, 26% UC, 6% indeterminate colitis) were included in the study. The median age was 43 (range, 16-86) years and 42% were male. Combination therapy with immunomodulators was employed in 18 patients (13 with thiopurines; 5 with methotrexate). Concomitant corticosteroid use was noted in 28%. Vedolizumab was administered every 8 weeks (n=36), 6 weeks (n=5) and 4 weeks (n=9). The median vedolizumab trough level was 14.75 (0-49.6) ug/mL. None of the patients had any detectable anti-vedolizumab antibodies. The median vedolizumab trough level was 13.8 (3.5-43) ug/mL and 14.8 (0-49.6) ug/mL in patients on and off corticosteroids, respectively (P=0.65). In patients on combination therapy with immunomodulators, the median vedolizumab trough level was 10.2 (0-49.5) ug/mL vs. 15.1 (3-49.6) ug/mL in patients on monotherapy (P=0.56). Endoscopic assessment and CRP levels were performed in 28 patients. MH was achieved in 18% (n=5). The median vedolizumab trough level was 11.2 (5.9-19.2) ug/mL and 9.1 (0-19.6) ug/mL in patients with and without MH, respectively (P=0.86). Patients with a normal CRP had a median vedolizumab trough level of 11.4 (3.5-38.7) ug/mL compared to 14.7 (0-49.6) ug/mL in those with high CRP (P=0.67). Vedolizumab trough levels resulted in change in clinical management in 80% of the cohort which included: decrease in dose interval in 33 patients, discontinuation of vedolizumab in 6 patients, and addition of an immunomodulator in 3 patients.
CONCLUSION(S): In a clinical cohort of IBD patients treated with vedolizumab, the median tough level was approximately 15 ug/mL, and no anti-drug antibodies were detected. Concomitant corticosteroid and immunomodulator therapy did not affect vedolizumab trough levels. No correlation between vedolizumab trough level with MH and CRP could be found. However, our results are limited by the small sample size.
P-112 Young Investigator Use of High Resolution Anorectal Manometry in UC Patients in Remission With Persistent Anorectal Symptoms
San Vicente Parada Elias, Gonzàlez Martinez Marina, Mayoral Zavala Arturo. 1H. de Especialidades, Centro Medico Nacional sXXI, IMSS, Mexico City, Mexico
BACKGROUND: A group of patients with UC continue to present symptomatology despite being in remission. Previous studies with conventional anorectal manometry in patients with active UC or remission, decreased rectal compliance was reported, and sphincter pressures within normal parameters. Because of inflammation-induced fibrosis in activity periods, decreased rectal compliance has been proposed as the cause of persistent symptomatology, in remission. Our aim was evaluated UC patients in remission with persistent anorectal symptoms with HRAM.
METHODS: Patients in remission in the Montreal and Mayo activity score for colonoscopy, from July 1, 2015 to June 31, 2016. Inclusion criteria:> 18 years, anorectal symptoms, signing of consent for HRAM. Exclusion criteria: alterations in proctological examination, loss of remission, anorectal surgery. A Manoscan 360 Sierra Scientific device with solid-state catheter, Manoview 2.1 software, was used. The mean volume for the first sensation, sensation and urgency of defecation, mean basal pressure of the sphincter and maximum contraction were reported. We analyzed the association between symptoms and HRAM results with the t test, and the association between symptoms and the extent of disease and evolution with X2. P=<0.5 to two tails was taken as significant. Analyzed with SPSS v22.
RESULTS: The inclusion criteria were 17 patients with anorectal symptoms, 9 accepted HRAM. The median age: 59 years, with 14 years of evolution, 66.7% female gender. Patients who accepted HRAM, according to Montreal: E3 44.4%, E1 33.3% and E2 22.2%; 66.7% were Mayo 1 and Mayo 0, 33.3%. 55.6% had tenesmus, fecal incontinence 22.2%, proctalgia 22.2% and constipation 22.2%. Two patients had constipation and tenesmus, one proctalgia and tenesmus. The median anal resting and squeeze of female patients: anal resting 71.25 mmHg (42.5-75.9), squeeze 132 mmHg (86.7-267.5). In male patients: anal resting 84.6 (82.6-92.3) and squeeze 251.4 mmHg (208.9-273.2). Volume for first sensation in female: 40 mL (30-50) and urge to defecate 150 mL (120-160). Volume in male: first sensation 50 mL (20-60) and urge to defecate 140 mL (140-150). Two presented paradoxical contraction. We found correlation of proctalgia with first sensation with P=0.210 and urge to defecate P=0.015. There was no relationship of symptoms with years of evolution or extension of UC.
CONCLUSION(S): The persistence of anorectal symptoms in patients with UC in remission is high. In our study, the most frequent symptom is tenesmus (55.6%). Patients had hyposensitivity and decreased rectal capacity. The anorectal symptoms are not related to years of evolution and extent of disease. There is correlation between proctalgia and changes in rectal capacity reported in HRAM.
P-113 Clinical significance of Anti-neutrophil Cytoplasmic Antibodies to Proteinase-3 (PR3-ANCA) in Patients With Ulcerative Colitis
Hamada Kensuke 1, Yoshino Takuya2, Sono Makoto1, Yazumi Shujiro1. 1Kitano Hospital, Osaka, Japan, 2Kyoto University, Graduate School of Medicine, Kyoto, Japan
BACKGROUND: Recently, many reports have been made on diagnostic value of anti-neutrophil cytoplasmic antibodies (ANCA) in patients with ulcerative colitis (UC). However, clinical significance of PR3-ANCA for UC is not well understood yet. We aim to analyze the clinical significance of PR3-ANCA in patients with UC.
METHODS: 74 patients with UC evaluated to proteinase-3-ANCA (PR3-ANCA) and myeloperoxidase-ANCA (MPO-ANCA) from July 2013 to July 2017 in our hospital were analyzed. Clinical remission was defined as less than 5 points of Lichtiger index, and endoscopic mucosal healing (MH) was defined as Mayo endoscopic score 0 or 1, respectively. We evaluated the ratio of positive for PR3- and MPO-ANCA in UC patients, and also evaluated the differences of clinical features between ANCA-positive and ANCA-negative groups.
RESULTS: Out of 74 UC-patients, 46 (62.1%) and 8 (10.8%) were positive for PR3-ANCA and MPO-ANCA, respectively. All cases positive for MPO-ANCA were also positive for PR3-ANCA. The ratio of patients with extensive colitis in the PR3-ANCA-positive group was significantly higher than that in the PR3-ANCA-negative group (71.7% and 46.6%, respectively; P=0.03). Moreover, the disease activity and MH rate of PR3-ANCA positive group was significantly higher and lower than those of PR3-ANCA negative group, respectively (disease activity: P=0.015, and MH rate: P<0.01). On the other hand, there was no significant difference in clinical characteristics, such as gender, age, serum level of C-reactive protein (CRP) and albumin levels, between the PR3-ANCA-positive and PR3-ANCA-negative group. However, regression analysis demonstrated that the titer of PR3-ANCA was significantly related with the serum level of albumin (r=0.396, P<0.01) and C-reactive protein (r=0.156, P<0.01), although there was no relationship between the titer of PR3-ANCA and Lichtiger index. In the sequent clinical course, the ratio of UC-patients requiring infliximab in the PR3-ANCA-positive group was also higher than that in the PR3-ANCA-negative group (17.4% and 0%, respectively; P=0.013). On the other hand, there was no significant difference in the ratio of UC-patients requiring surgery between the PR3-ANCA-positive and the PR3-ANCA-negative group (12.2% vs 0%, respectively; P>0.05).
CONCLUSION(S): PR3-ANCA may be the prognostic factor for refractory UC requiring intensive therapies, because there is less rate of MH in the group of PR3-ANCA positive, apparently.
P-114 Young Investigator IBD – Is It a Risk Factor for the Diagnosis of Hepatic Steatosis?
Arieira Cátia 1, Monteiro Sara2, Xavier Sofia3, Dias de Castro Francisca4, Magalhães Joana5, Marinho Carla6, Cotter José4. 1Hospital da Senhora da Oliveira, Guimarães, Portugal, 2Gastroenterology Department, Hospital Senhora da Oliveira-Guimarães, Guimarães, Portugal, 3Hospital da Senhora da Oliveira, Guimarães, Portugal, 4Gastroenterology Department, Hospital Senhora da Oliveira-Guimarães, Guimarães, Portugal, 5Gastroenterology Department, Hospital da Senhora da Oliveira-Guimarães, Guimarães, Portugal, 6Hospital da Senhora da Oliveira, Guimarães, Portugal
BACKGROUND: Although is not yet established, recent studies suggest an increase prevalence of hepatic steatosis (HS) in patients with inflammatory bowel disease (IBD). Factors such as chronic inflammation, previous surgeries, drug-induced hepatotoxicity, malnutrition and intestinal dysbiosis seem to be involved in the pathogenesis of this disease. Aim: To assess the frequency of HS in IBD patients quantified by CAP (controlled attenuation parameter) and by clinical-analytical methods: Hepatic Steatosis Index (HSI) and Fatty Liver Index (FLI). A secondary aim is to investigate risk factors associated with HS in IBD patients.
METHODS: Cross-sectional study that included consecutive outpatients that were observed in our department between January and March 2017. Patients with known liver disease or alcohol habits were excluded. HS was defined as HSI ≥ 36 or FLI ≥ 60 or CAP> 248.
RESULTS: 149 patients included with mean age 40.7 ± 13 years, 83 female (55.7%), 59.7% with Crohn's disease (CD). 62 patients (41.7%) had CAP> 248, 20 (13.4%) FLI> 60 and 40 (26.8%) HSI> 36. There were no differences in the mean CAP value (244 ± 54.2), HSI (33.3 ± 5.18), and FLI (31.5 ± 25.3) among patients with CD and Ulcerative Colitis. We found that patients with CAP> 248 were more frequently obese (27.4% vs 0% p <0.001), males (54.8% vs. 36.8% P=0.029) and presented more frequently metabolic syndrome (25% vs 4.6% p <0.001). Regarding the IBD factors, patients with HS had a higher frequency of previous surgeries (30.6% vs16.1% P=0.035). There were no differences between hospitalization, duration of the disease, use of corticosteroids or other IBD treatments.
CONCLUSION(S): In our cohort, the frequency of HS varied between 13.4% and 41.7% defined by non-invasive methods. We found that the presence of metabolic syndrome and obesity were more frequent in patients with HS. Regarding factors related to IBD, patients with previous history of surgery were more frequently diagnosed with HS.
P-115 Young Investigator Is Contrast-Enhanced Ultrasonography the Best Non-invasive Method to Evaluate Ileal Crohn’s Disease Activity?
Monteiro Sara, Dias de Castro Francisca, Leite Sílvia, Magalhães Joana, Moreira Maria João, Cotter José. Gastroenterology Department, Hospital Senhora da Oliveira-Guimarães, Guimaraes, Portugal
BACKGROUND: Contrast-enhanced ultrasonography (CEUS) is an imaging technique that has been used to monitor patients with Crohn's Disease (CD). Our aim was to determine the performance of conventional US and CEUS and other non-invasive parameters such as clinical activity and analytical biomarkers to detect ileal CD inflammatory activity assessed by ileocolonoscopy.
METHODS: Thirty patients with known ileal CD were evaluated. All patients underwent a conventional US followed by a CEUS using a microbubble contrast agent (SonoVue®). US examinations was performed using a Hitachi HI VISION Avius®, employing a linear abdominal transducer. Qualitative and quantitative parameters from the sonographic analysis included maximum bowel wall thickness, vascularity pattern by Doppler US and quantitative measurements of contrast bowel wall enhancement using CEUS (peak intensity and time to peak). Disease small bowel activity was assessed by ileocolonoscopy (reference) and patients were graded as inactive (normal or mild disease) or active (moderate or severe inflammation). Clinical disease activity was assessed by the Harvey–Bradshaw Index (HBI). Fecal calprotectin (FC) and C reactive protein (CRP) were performed within 1 week from CEUS and correlated with ileal inflammatory activity assessed by ileocolonoscopy.
RESULTS: Endoscopic disease severity was as follow: normal or mild in 14 patients (46.7%), moderate or severe in 16 patients (53.3%). Sixteen patients (53.3%) had significant clinical activity (HBI≥5 points). No association was found between clinical activity by HBI and endoscopic disease activity (P=0.77). In patients with moderate and severe endoscopic activity, mean FC tended to be higher than in patients with inactive disease, but the difference was not statistically significant (878.6 μg/L vs 809.6 μg/L, P=0.78).
No association was found between mean CRP and endoscopic activity (23.1 vs 23.9, P=0.95).
In patients with active endoscopic disease, wall bowel thickness of the terminal ileum was higher than in patients with inactive disease, but this result was not statistically significant (6.5 mm vs 5.7 mm, P=0.33). No association was found between the presence of moderate to severe vascularity by Doppler (P=0.15), loss of normal stratification of the bowel wall (P= 0.596), mesentery hypertrophy (P= 0.69), mesenteric lymph nodes (P= 0.34) and disease activity. For CEUS, the peak intensity was related with disease severity (19.2 vs 8.7, P=0, 01) with a good capability to predict endoscopic activity in ileoscopy (area under the ROC curve 0.8, 95% CI 0.63-0.96). The time to peak could not predict endoscopic activity in ileoscopy (21.4 sec vs 20.9 sec, P=0.78).
CONCLUSION(S): Clinical and analytical parameters are not sufficient to predict endoscopic activity in the terminal ileum. Conventional US is also not capable to predict endoscopic activity, being contrast-enhanced US an excellent non-invasive method for this purpose. CEUS peak intensity is a non-invasive and valuable parameter for an accurate detection of ileal inflammatory activity in CD leaving open, in the future, the possibility to monitor the therapeutic response.
P-116 Faecal Extracts Biomarkers in IBD Patients: Is It Useful?
Neto Manoel. Federal University of Alagoas, Maceio, Brazil
BACKGROUND: Crohn Disease (CD) and Ulcerative Colitis (UC) are the main IBD known diseases related to genetic and environmental factors. Nowadays the diagnostic is invasive and onerous for the patient. The assessment of metabolite profiles in biofluids has become a powerful method for the detection of biomarker molecules and disease mechanisms. Metabolic reactions initiated by the host or gut microbiota can lead to identification of a marker metabolites present in biological fluids that allow differentiation between health and disease. A non-invasive approach of diagnosing IBD may also be preferable over endoscopy which is not without risk, although serious complications are reportedly low. Non-invasive fecal and serologic markers with variable specificity and sensitivity for IBD are already in use and our results prove that is a possible way to pursue and initiate a new alternative to findings new biomarker in inflammatory bowel disease.
METHODS: This project was approved by Ethic Committee of the University Hospital of Alagoas. All subjects were out patients from the University Hospital of Alagoas Prof. Alberto Antunes, Brazil. Feces water extracts from fourteen patients with advanced IBD and ten healthy control subjects. Samples were analysed by NOESY 1D 1H NMR technique in a Bruker Avance 400MHZ Spectrometer. All spectra were normalized and submitted to multivariate data analysis of PLS-DA (tools in MATLAB software). Cross validation analysis has been carried out and discriminant metabolites were selected by ANOVA (P<0.05). Metabolites were identified by comparison with data of the literature.
RESULTS: NMR Spectra have shown metabolites such as: butyrate, propionate, ethanol, lactate, leucine, alanine, acetate, methanol, tyrosine, oxaloacetate, glycine, succinate and gamma-aminobutyrate. After multivariate data analysis, cross validation has shown 90% confidence. PLS-DA was 0,75 for the 1stC and 0,49 for the 2ndC. ANOVA discriminant analysis has shown that lactate (P=0,01) and leucine (P=0.02) were higher in IBD patients, and ethanol (P=0.04) was higher in healthy subjects.
CONCLUSION(S): The faecal water analysis by 1H NMR 1D spectrometry has shown to be very powerful to differentiate between IBD patients with healthy subjects when comparing the spectra profile of both groups after multivariate data analysis using PLS-DA statistical methodology.
P-117 Young Investigator Level of Antibodies to Type I Collagen in Ulcerative Colitis
Mukhametova Dilyara 1, Abdulganieva Diana1, Zinkevich Oleg2, Saphina Nellya2, Koporulina Marina2, Odintsova Alfiya3. 1Kazan State Medical University, Kazan, Russia, 2Kazan State Medical Academy, Kazan, Russia, 3Republican Clinical Hospital, Kazan, Russia
BACKGROUND: Immunological disorders play an important role in the pathogenesis of ulcerative colitis (UC). Collagen is the main component of the intercellular matrix of connective tissue. It can be assumed that the immune disorders leading to the production of autoantibodies to collagen play a role in the pathogenesis of UC. Aim: to study the level of IgM and IgG to type I collagen (COL1) in UC.
METHODS: We prospectively included 61 patients with UC and 30 healthy controls. Mean age in UC was 37±1,5 years and in control group – 30±1,5. Severity of UC was assessed by Mayo score: remission – 5, mild – 25, moderate –26, severe – 5. Extraintestinal manifestations of UC were in 24 patients (39%). Level of serum IgM and IgG to COL1 was assessed by enzyme immunoassay.
RESULTS: In active UC levels of IgM to COL1 was increased (0,17 [0,10; 0,20] mkg/ml) compared with healthy (0,09 [0,07; 0,12] mkg/ml; p<0,01). The difference between remission (0,1 [0,09; 0,19] mkg/ml) and exacerbation, remission and control group was not detected (P>0,05). In patients with severe UC IgM to COL1 was 0,19 [0,18; 0,25] mkg/ml, which was higher than in moderate UC – 0,12 [0,08; 0,17] mkg/ml (p<0,05) and mild – 0,18 [0,11; 0,20] mkg/ml (p>0,05). There was a tendency to increase of IgM to COL1 in patients with extraintestinal manifestations (0,17 [0,10; 0,22] mkg/ml) than without them (0,12 [0,09; 0,18] mkg/ml). The level of IgG to COL1 in active UC (24,69 [16,36; 99,12] mkg/ml) was higher than in the control group 11,36 [6,93; 19,83] (p<0,05) and remission - 13,15 [8,88; 26,21] (p>0,05). There was not revealed the difference of IgG levels depending on the severity of disease. There was a tendency to increase of IgG to COL1 in patients with extraintestinal manifestations (16,18 [9,46; 26,21] mkg/ml), than without them (12,78 [8,81; 28,31] mkg/ml). There was increasing of ESR (r=0,36; P<0,05) and leukocytosis (r=0,32; P<0,05) with increase of IgM level to COL1.
CONCLUSION(S): In active UC, the level of serum antibodies of class IgM and IgG to COL1 increased compared with healthy. The maximum increase was found in the group of patients with severe relapse and in the presence of extraintestinal manifestations.
P-118 Factors Influencing Best Practices in Treating IBD: Results From a Predictive Modeling Analysis of Educational Outcomes Data
Reiter Jamie, Perez Jan, Tordoff Sharon, Faler Whitney. CME Outfitters, LLC, Bethesda, Maryland
BACKGROUND: Healthcare providers (HCPs) treating patients with inflammatory bowel disease (IBD) are tasked with balancing treatment efficacy and safety with individual patient preferences, including goals and cost. These challenges provided an opportunity for a continuing medical education (CME) activity that highlighted the risks/benefits of treatment options, cost, clinical considerations related to disease progression, and benefits of a proactive, personalized approach. The primary goals of the CME activity were to improve HCP knowledge, competence, and behavior surrounding these issues, which will ultimately translate to better patient outcomes. The goal of the present study was to use predictive modeling to determine factors that influence HCP practice behaviors to gain a better understanding of what motivates or prevents best practice implementation.
METHODS: Educational outcomes data were obtained from a CME activity on IBD, which consisted of a faculty-led webcast based on a live symposium at the Academy of Managed Care Pharmacy annual meeting. HCP surveys assessing knowledge, confidence, and behavior were administered before, immediately following, and 3 months following the activity. An analysis using PredictCME (based on chi-square automatic interaction detection) was conducted on data from the pre-activity survey, which included a behavior question related to utilizing a proactive, personalized approach weighing risk/benefit and cost when making treatment decisions. This was used as the response variable in the model. Predictor variables included demographics, knowledge, evaluation, and self-rating of ability for integrating concepts about disease progression into decision making.
RESULTS: Over 4,400 HCPs participated in the live and enduring versions of activity, with 168 HCPs participating in the pre-survey used for the analysis. Findings revealed self-rating of ability to be the strongest predictor of behavior (X2(1)=24.70, p<.001), with those who rated their ability as good or excellent being more likely to perform the practice behavior. A secondary predictor, affecting only those who rated their ability as good or excellent, was overall knowledge (X2(1)=13.98, p<.01), with those scoring 50% correct or greater being more likely to perform the practice behavior.
CONCLUSION(S): The strongest predictor of behavior was self-rating of ability for integrating concepts about disease progression into decision making. We view this as a similar measure to self-rated confidence. Therefore, the results from the PredictCME analysis suggest that building HCP confidence is an important component of ensuring best practices are performed for the management of patients with IBD. Improving HCP knowledge was also an important component of ensuring best practices are performed. Future CME activities will be designed to maximize HCP confidence and knowledge of topics relevant for improving practice behaviors in IBD.
P-119 Red Blood Cell Distribution Width and It's Association With Inflammatory Bowel Disease Management
Strauss Alexandra1; Rosario Michelle 2, Patel Harsh3, Caire Michael4, Kumar Ambuj5, Brady Patrick6. 1Johns Hopkins, Baltimore, Maryland, 2University of South Florida, Tampa, Florida, 3University of South Florida Morsani College of Medicine, Tampa, Florida, 4TGH Transplant & Specialty Services, Tampa, Florida, 5University of South Florida, Tampa, Florida, 6USF Health Division of Digestive Diseases and Nutrition, Tampa, Florida
BACKGROUND: Inflammatory Bowel Diseases (IBD) require close monitoring over a person’s lifetime to prevent long term negative sequelae and promote better outcomes. At present, the gold standard monitoring tool is endoscopic evaluation. Several non-invasive alternatives have been evaluated, however their benefit is unclear. The data we present evaluates red blood cell distribution width (RDW) as a predictive measure of active disease prior to endoscopy and if it is a useful prognostic tool. To date, the literature has noted a relationship between a high RDW and level of activity in many chronic inflammatory diseases, including IBD. This has been attributed to both the inflammatory nature of these diseases along with the associated anemia. Lastly, the benefits of RDW lie in its non-invasive nature and that it comes readily available in a commonly ordered lab test, a complete blood count (CBC), at no additional cost.
METHODS: Data on patients with IBD who had an RDW within one month prior to colonoscopy from January 1, 2015 to December 31, 2015 was pulled in a retrospective chart review. Both clinical and descriptive data were obtained for the study as well as patients’ Harvey Bradshaw Indices and Mayo Scores. Endoscopic data including the Mayo Endoscopic Score, Simplified Endoscopic Scoring System, and histologic data were also noted. Each endoscopy report was reviewed by two separate Gastroenterologists. Data exclusion criteria were: patients with hemoglobinopathies, organ transplant, hemoglobin less than 7, and for patients under the age of 18. The Mann-Whitney U Test was used to compare the difference among RDW values. Correlation between continuous variables was assessed using the Spearman Correlation Test. Statistical significance for all comparisons was set at 5%.
RESULTS: Sixty patients met inclusion criteria. Median age for the cohort was 35 years (SD=17.1). Evaluating other patient demographics, 46.9% of participants were males and most were Caucasian (68%). There was a relationship between RDW and need for medication escalation after endoscopy. Medication increase post-colonoscopy was more frequently noted in patients with RDWs above the normal value. There was a significant difference in RDW between patients with Ulcerative Colitis who had a change in management compared with those who did not require a change in treatment (U=18, P=0.027). Similarly, there was a significant difference in RDW value for patients with Crohn’s Disease who underwent change in treatment compared with patients who did not (U=101, P=0.043).
CONCLUSION(S): Based on the findings from our retrospective data collection, elevated RDW was associated with the need for escalation of treatment in patients with IBD. This relationship was present on subgroup analysis for patients with Ulcerative Colitis and with Crohn’s Disease.
P-120 Pseudopolyposis: A Manifestation of Isolated Upper Gastrointestinal Crohn’s Disease
Aggarwal Soorya 1, Cavanagh Yana2, Shulik Oleg3, Grossman Matthew4, Galeano Narmer4. 1Lehigh Valley Health Network at Cedar Crest, Allentown, Pennsylvania, 2New York Medical College at St. Joseph's Regional Medical Center, Paterson, New Jersey, 3Georgetown University Hospital, Washington, District of Columbia, 4St. Joseph’s Regional Medical Center, Paterson, New Jersey
BACKGROUND: Inflammatory Bowel Disease (IBD) likely results from a complex interplay of genetic predisposition, environmental and psychosocial factors and a dysregulation of gut microbiota [1-2]. Isolated upper gastrointestinal tract (UGI) CD has not been widely described and has no standardized societal recommendations for diagnosis or management, particularly in the pediatric patient . Standard IBD evaluation including serological testing, imaging and endoscopy may not be as useful in isolated UGI CD as this population manifests limited symptomatology and standard evaluation is most fruitful in patients with a high pre-test probability of CD [4-5]. The lack of classic symptoms may result in a low clinical suspicion and diagnostic delay . Modalities such as lift assisted endoscopic mucosal resection (EMR) may increase diagnostic yield in this patient population.
RESULTS: An 18-year-old male presented with persistent iron-deficiency anemia. He had no significant family history or personal GI complaints. Extensive out patient evaluation including IBD serology was unremarkable except for a positive qualitative fecal calprotectin. Index endoscopic evaluation at revealed numerous polypoid lesions in the stomach and duodenum with underlying erythema. However, pathology evaluation was non-specific. Repeat endoscopy with lift assisted EMR successfully sampled inflammatory polyps, focal crypt abscesses, chronic inflammation in the lamina propria, glandular epithelial reactive changes, superficial foveolar epithelial regenerative changes, and villous blunting of the small bowel.
CONCLUSIONS(S): Both true extra-colonic polyps and inflammatory polyps can present with anemia. Furthermore, both syndromic polyposis and inflamed polypoid tissue can grossly appear similar. As such, polyposis syndromes could not initially be excluded in our pediatric patient, in the setting of the gross endoscopic findings . We utilized EMR to increase the diagnostic yield of our tissue specimen and confirm the distinct histological findings associated with IBD that were present in our patient [8-10]. A high index of clinical suspicion should be maintained in pediatric males presenting with unexplained anemia, particularly IDA. A 2014 meta-analysis cited an up to 27% prevalence of clinically significant anemia in patients with CD . Additionally, considering our patients elevated fecal calprotectin, which has been shown to have a 97% sensitivity for IBD in the pediatric population, the overall clinical picture was highly suggestive of underlying IBD, despite negative serology . A diligent workup including laboratory evaluation, imaging and endoscopy with adequate tissue sampling should be obtained to establish pathology and dictate subsequent management.
P-121 Ileal Pouch of Ulcerative Colitis Patients Exhibit Impaired Autophagy
Paiva Nielce1, Pascoal Livia1, Negreiros Leandro1, Portovedo Mariana1, Coope Andressa1, Ayrizono Maria de Lourdes2, Coy Claudio1, Milanski Marciane1; Leal Raquel 1. 1University of Campinas, Campinas, Brazil, 2Unicamp, Campinas, Brazil
BACKGROUND: Total rectocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgery of choice for patients with ulcerative colitis (UC) that are refractory to clinical treatment and for familial adenomatous polyposis (FAP) with many rectal polyps. The main complication after this procedure is the pouch inflammation (pouchitis) that can affect up to 45 percent of patients who are submitted to IPAA for UC, and only five percent of the FAP patients who undergo the same procedure. Previous studies have shown increased pro-inflammatory cytokines in the ileal pouch (IP) mucosa of UC patients, even in the absence of clinical, endoscopic and histological inflammation. Autophagy is an evolutionarily conserved catabolic pathway that consists of selective degradation of cellular components and a homeostatic mechanism that protects cells exposed to stress situations (toxins, starvation), and defects in this pathway have been reported in inflammatory bowel diseases. However, there are no studies on the IP. Therefore, we studied markers for autophagy in the IP mucosa of UC and FAP patients comparing them to controls with a normal distal ileum.
METHODS: Sixteen patients with IP in "J" shape, asymptomatic and with endoscopically normal mucosa were evaluated. The control group consisted of eight patients with normal colonoscopy. Gene expression was analyzed by qPCR and protein levels by immunoblotting and immunofluorescence. This study was approved by the Ethics Committee of the University of Campinas and was performed in accordance with the Declaration of Helsinki. All results were reported as means ± SEM. Data were analyzed by non-parametric Test, comparing all groups. The level of significance was set at P<0.05.
RESULTS: There was a significant decrease in the transcriptional levels of ATG5, MAP1LC3A and BAX in the FAP group (P<0.05). There was also a decrease in the protein level of Beclin-1 in the UC and FAP compared to the control group (P<0.05). Although the LC3II levels by immunoblot were higher in the UC group, total LC3 and LC3/p62 co-localization were lower in the immunofluorescence analysis in the UC and FAP compared to the control group (P<0.05). Corroborating to these results, there was an increase of p62 by immunoblot in the UC group, compared to controls (P<0.05).
CONCLUSION(S): These results indicate impaired macroautophagy mechanism in the IP. In FAP, decreased autophagy may be related to impaired apoptosis, otherwise in UC, may be mainly due to increased Toll-Like Receptors (TLR) activation. These findings may explain the inflammation predisposition, mainly in the IP mucosa of UC patients.
Acknowledgments: We thank FAPESP (São Paulo Research Foundation) for financial support. Negreiros LMV (co-author) received scholarship from FAPESP. We are grateful to Prof. Tristan Torriani for English grammar revision. We thank Francesca Ramos and José Diego Botezelli for technical assistance and the staff of the Life Sciences Core Facility (LaCTAD) from State University of Campinas (UNICAMP), for the Cell Biology analysis.
P-122 Preoperative Serum Vedolizumab Levels Do Not Impact Postoperative Outcomes in Inflammatory Bowel Disease (IBD)
Lopez Nicole 1, Zaghiyan Karen2, Melmed Gil3, McGovern Dermot3, Jain Anjali4, Landers Carol1, Fleshner Phillip3. 1Cedars-Sinai, Los Angeles, California, 2Cedars Sinai Medical Center, Los Angeles, California, 3Cedars Sinai Medical Center, Los Angeles, California, 4Prometheus Labs Inc., San Diego, California
BACKGROUND: Although biological therapy has revolutionized the medical management of IBD, a crucial concern is whether patients undergoing major abdominal surgery after drug exposure are at increased risk of early postoperative complications. Studies reporting on the association of preoperative vedolizumab therapy use and postoperative outcomes in IBD have been published with conflicting results. Serum levels of anti-TNF drugs have been used as a surrogate for biologic effect on inflammatory mechanisms and have been correlated with postoperative outcomes. In a similar fashion, we sought to clarify associations between serum vedolizumab levels and postoperative outcomes in IBD patients.
METHODS: IBD patients on vedolizumab, with serum drawn within 7 days before surgery, were identified from a prospectively collected IRB-approved database. Serum vedolizumab levels were measured by investigators blinded to clinical outcomes using the homogenous mobility shift assay (Prometheus Laboratories Inc.). Patients were divided into 2 groups according to serum levels: Group 1 (undetectable vedolizumab levels; ≤1.8 mcg/ml)) and Group 2 (detectable serum vedolizumab levels; >1.8 mcg/ml). To assess whether a higher level of vedolizumab affected outcomes, Group 2 was divided further into high and low levels as determined by median detectable serum level. Postoperative outcomes, including the Comprehensive Complication index (CCI)), within 30 days of surgery were collected prospectively and compared among groups. Categorical variables were analyzed using Fisher’s exact test and continuous variables analyzed with Student’s t-test.
RESULTS: The study cohort of 35 patients had a median age of 29 (range, 14-62) years and included 18 (51%) males. Indications for surgery were Crohn’s disease (n=18;51%), ulcerative colitis (n=14;40%) or indeterminate colitis (n=3;9%). Index procedures included subtotal colectomy with ileostomy (n=10;29%), small bowel/ileocolic resection (n=9; 26%) and ileal pouch-anal anastomoses (n=8;23%). Serum vedolizumab levels were detectable in 23 (66%) patients and not detectable in 12 (34%) patients. Median detectable serum vedolizumab level at the time of surgery was 12.6 mcg/ml (range, 1.9-54.4). Twelve (34%) patients had low detectable levels and 11 (31%) had high detectable levels. Groups 1 and 2 were similar in all preoperative characteristics. There were no postoperative deaths. There were no significant differences between groups in regards to overall postoperative morbidity (13% vs. 42%; P=0.09), infectious complications (4% vs. 17%; P=0.26), 30-day readmission rates after surgery (13% vs. 33%; P=0.19), or CCI (1.9 vs. 5.1; P=0.07). Finally, among patients with detectable serum vedolizumab levels, there was no association between level of vedolizumab (high vs. low) and overall postoperative morbidity (18% vs. 17%; P=1), infectious complications (0% vs. 8%; P=1), 30-day readmission rates (18% vs. 8%; P=0.59) or CCI (0.79 vs 2.9; P=0.07) after surgery.
CONCLUSION(S): This first-ever study of serum vedolizumab levels in surgical patients showed that the presence and magnitude of serum drug levels do not adversely influence postoperative outcomes in IBD patients. Contrary to other studies, there appears to be no deleterious effect of preoperative vedolizumab use in IBD patients requiring surgery.
P-123 Comparison of the Expression of Metalloproteinases and Their Tissue Inhibitors in Ulcerative Colitis and Colon Diverticulitis
Nemeth Zoltan 1, Barratt-Stopper Patricia1, Hakakian Daniel2, Rolandelli Rolando3. 1Morristown Medical Center, Department of Surgery, Morristown, New Jersey, 2Morristown Medical Center, Morristown, New Jersey, 3Morristown Medical Center, Department of Surgery, Morristown, New Jersey
BACKGROUND: Various cell types of the gastrointestinal tract express matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). It has been proposed that the imbalance between these enzymes and their inhibitors can lead to extracellular matrix remodeling, mucosal damage and structural changes in colonic tissue. Therefore, we wanted to explore and compare the expression levels of several members of the MMP and TIMP families in patients with ulcerative colitis (UC) or diverticulitis who underwent a surgical colon resection.
METHODS: Messenger RNA (mRNA) expression levels were compared using real-time PCR in both inflamed and non-inflamed bowel specimens from patients with active UC (n=20) or diverticulitis (n=23) and without these diseases (control, n=25).
RESULTS: In both UC and diverticulitis, MMP-1, and TIMP-2 transcript levels were higher than in control. Interestingly, UC specimens showed significantly higher MMP-2, -3, -9, -10 and -13 mRNA expression, while diverticulitis specimens did not. However, in diverticulitis, MMP-28 transcript levels as well as TIMP-1, and -3 mRNA expression were significantly increased when compared to both UC and control. Generally, the highest levels of the MMPs were found in the inflamed areas of UC and diverticulitis, while TIMPs were more up-regulated in the adjacent, non-diseased areas.
CONCLUSION(S): UC and diverticulitis have a different MMP and TIMP expression pattern, with UC having a generally stronger and wider array of MMP activity. The pharmacological regulation of these enzymes and their natural tissue inhibitors may allow for more effective and personalized therapies.