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  • Review Article
  • Published:

Current best practice for disease activity assessment in IBD

Nature Reviews Gastroenterology & Hepatology volume 13, pages 567–579 (2016)Cite this article

Subjects

Key Points

  • Objective assessment of disease activity in IBD is important for guiding subsequent therapy as part of a 'treat to target' strategy

  • Multiple domains of disease activity assessment exist in IBD (symptoms, endoscopy, histology, radiology, biomarkers and quality of life), and targets should be recognized as goals for therapy within each domain

  • Confusing terminology and the use of composite indices (combining symptom assessment with objective measurements of quality of life or inflammation) confound the formal evaluation of disease activity

  • Biomarkers are useful adjuncts to monitor disease activity in both ulcerative colitis and Crohn's disease

  • Assessment of quality of life is an important aspect of medical decision-making, as improving quality of life is a major goal of therapy

Abstract

Therapeutic advances in the management of IBD have led to a paradigm shift in the assessment of IBD disease activity. Beyond clinical remission, objective assessment of inflammation is now critical to guiding subsequent therapy as part of a 'treat to target' strategy. Multiple domains of disease activity assessment in IBD exist, each of which has its merits, although none are perfect. The aim of this Review is to comprehensively evaluate measures of disease activity in both ulcerative colitis and Crohn's disease, including clinical, endoscopic, histological and radiological assessment tools, as well as the use of biomarkers and quality of life evaluation. A subjective appraisal of the best indices for use in clinical practice is provided, based on index validation, responsiveness and experience in clinical trials, international specialist opinion, and practicality and suitability for use in clinical practice. This Review aims to enable the reader to gain confidence in IBD disease activity assessment and to give ready access to the necessary tools.

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Figure 1: Domains of disease activity assessment.

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References

  1. Dignass, A. et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 2: current management. J. Crohns Colitis 6, 991–1030 (2012).

    Article  PubMed  Google Scholar 

  2. Dignass, A. et al. The second European evidence-based consensus on the diagnosis and management of Crohn's disease: current management. J. Crohns Colitis 4, 28–62 (2010).

    Article  CAS  PubMed  Google Scholar 

  3. Peyrin-Biroulet, L. et al. Selecting therapeutic targets in inflammatory bowel disease (STRIDE): determining therapeutic goals for treat-to-target. Am. J. Gastroenterol. 110, 1324–1338 (2015).

    Article  CAS  PubMed  Google Scholar 

  4. Walsh, A. J. et al. Comparing disease activity indices in ulcerative colitis. J. Crohns Colitis 8, 318–325 (2014).

    Article  CAS  PubMed  Google Scholar 

  5. Bryant, R. V., Winer, S., Travis, S. P. & Riddell, R. H. Systematic review: histological remission in inflammatory bowel disease. Is 'complete' remission the new treatment paradigm? An IOIBD initiative. J. Crohns Colitis 8, 1582–1597 (2014).

    Article  CAS  PubMed  Google Scholar 

  6. Marchal-Bressenot, A. et al. Development and validation of the Nancy histological index for UC. Gut http://dx.doi.org/10.1136/gutjnl-2015-310187 (2015).

  7. Travis, S. P. et al. Once-daily budesonide MMX in active, mild-to-moderate ulcerative colitis: results from the randomised CORE II study. Gut 63, 433–441 (2014).

    Article  CAS  PubMed  Google Scholar 

  8. Travis, S. P. et al. Developing an instrument to assess the endoscopic severity of ulcerative colitis: the Ulcerative Colitis Endoscopic Index of Severity (UCEIS). Gut 61, 535–542 (2012).

    Article  PubMed  Google Scholar 

  9. Travis, S. P. et al. Reliability and initial validation of the ulcerative colitis endoscopic index of severity. Gastroenterology 145, 987–995 (2013).

    Article  PubMed  Google Scholar 

  10. Walmsley, R. S., Ayres, R. C., Pounder, R. E. & Allan, R. N. A simple clinical colitis activity index. Gut 43, 29–32 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Schroeder, K. W., Tremaine, W. J. & Ilstrup, D. M. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N. Engl. J. Med. 317, 1625–1629 (1987).

    Article  CAS  PubMed  Google Scholar 

  12. Sandborn, W. J. et al. Repifermin (keratinocyte growth factor-2) for the treatment of active ulcerative colitis: a randomized, double-blind, placebo-controlled, dose-escalation trial. Aliment. Pharmacol. Ther. 17, 1355–1364 (2003).

    Article  CAS  PubMed  Google Scholar 

  13. Turner, D. et al. Development, validation, and evaluation of a pediatric ulcerative colitis activity index: a prospective multicenter study. Gastroenterology 133, 423–432 (2007).

    Article  PubMed  Google Scholar 

  14. Truelove, S. C. & Witts, L. J. Cortisone in ulcerative colitis; final report on a therapeutic trial. Br. Med. J. 2, 1041–1048 (1955).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Turner, D. et al. A systematic prospective comparison of noninvasive disease activity indices in ulcerative colitis. Clin. Gastroenterol. Hepatol. 7, 1081–1088 (2009).

    Article  PubMed  Google Scholar 

  16. D'Haens, G. et al. A review of activity indices and efficacy end points for clinical trials of medical therapy in adults with ulcerative colitis. Gastroenterology 132, 763–786 (2007).

    Article  CAS  PubMed  Google Scholar 

  17. Dignass, A. et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 1: definitions and diagnosis. J. Crohns Colitis 6, 965–990 (2012).

    Article  PubMed  Google Scholar 

  18. Dinesen, L. C. et al. The pattern and outcome of acute severe colitis. J. Crohns Colitis 4, 431–437 (2010).

    Article  PubMed  Google Scholar 

  19. Neurath, M. F. & Travis, S. P. Mucosal healing in inflammatory bowel diseases: a systematic review. Gut 61, 1619–1635 (2012).

    Article  CAS  PubMed  Google Scholar 

  20. Sandborn, W. J. et al. A review of activity indices and efficacy endpoints for clinical trials of medical therapy in adults with Crohn's disease. Gastroenterology 122, 512–530 (2002).

    Article  PubMed  Google Scholar 

  21. Froslie, K. F., Jahnsen, J., Moum, B. A. & Vatn, M. H. Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort. Gastroenterology 133, 412–422 (2007).

    Article  PubMed  Google Scholar 

  22. Ardizzone, S. et al. Randomised controlled trial of azathioprine and 5-aminosalicylic acid for treatment of steroid dependent ulcerative colitis. Gut 55, 47–53 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Rutgeerts, P. et al. Scheduled maintenance treatment with infliximab is superior to episodic treatment for the healing of mucosal ulceration associated with Crohn's disease. Gastrointest. Endosc. 63, 433–442 (2006).

    Article  PubMed  Google Scholar 

  24. Schnitzler, F. et al. Mucosal healing predicts long-term outcome of maintenance therapy with infliximab in Crohn's disease. Inflamm. Bowel Dis. 15, 1295–1301 (2009).

    Article  PubMed  Google Scholar 

  25. Colombel, J. F. et al. Early mucosal healing with infliximab is associated with improved long-term clinical outcomes in ulcerative colitis. Gastroenterology 141, 1194–1201 (2011).

    Article  CAS  PubMed  Google Scholar 

  26. Rutter, M. et al. Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis. Gastroenterology 126, 451–459 (2004).

    Article  PubMed  Google Scholar 

  27. Corte, C. J. et al. Association between the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and outcomes in acute severe ulcerative colitis. J. Crohns Colitis http://dx.doi.org/10.1093/ecco-jcc/jjv047 (2015).

  28. Ikeya, K. et al. The ulcerative colitis endoscopic index of severity more accurately reflects clinical outcomes and long-term prognosis than the mayo endoscopic score. J. Crohns Colitis http://dx.doi.org/10.1093/ecco-jcc/jjv210 (2015).

  29. Baars, J. E., Nuij, V. J., Oldenburg, B., Kuipers, E. J. & van der Woude, C. J. Majority of patients with inflammatory bowel disease in clinical remission have mucosal inflammation. Inflamm. Bowel Dis. 18, 1634–1640 (2012).

    Article  PubMed  Google Scholar 

  30. Bessissow, T. et al. Prognostic value of serologic and histologic markers on clinical relapse in ulcerative colitis patients with mucosal healing. Am. J. Gastroenterol. 107, 1684–1692 (2012).

    Article  PubMed  Google Scholar 

  31. Bitton, A. et al. Clinical, biological, and histologic parameters as predictors of relapse in ulcerative colitis. Gastroenterology 120, 13–20 (2001).

    Article  CAS  PubMed  Google Scholar 

  32. Bryant, R. V. et al. Beyond endoscopic mucosal healing in UC: histological remission better predicts corticosteroid use and hospitalisation over 6 years of follow-up. Gut 65, 408–414 (2015).

    Article  CAS  PubMed  Google Scholar 

  33. Gupta, R. B. et al. Histologic inflammation is a risk factor for progression to colorectal neoplasia in ulcerative colitis: a cohort study. Gastroenterology 133, 1099–1105 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  34. Mosli, M. H. et al. Development and validation of a histological index for UC. Gut http://dx.doi.org/10.1136/gutjnl-2015-310393 (2015).

  35. Magro, F. et al. European consensus on the histopathology of inflammatory bowel disease. J. Crohns Colitis 7, 827–851 (2013).

    Article  CAS  PubMed  Google Scholar 

  36. Mosli, M. H. et al. Reproducibility of histological assessments of disease activity in UC. Gut 64, 1765–1773 (2015).

    Article  PubMed  Google Scholar 

  37. Bressenot, A. et al. Comparing histological activity indexes in UC. Gut 64, 1412–1418 (2015).

    Article  PubMed  Google Scholar 

  38. Riley, S. A., Mani, V., Goodman, M. J., Dutt, S. & Herd, M. E. Microscopic activity in ulcerative colitis: what does it mean? Gut 32, 174–178 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Geboes, K. et al. A reproducible grading scale for histological assessment of inflammation in ulcerative colitis. Gut 47, 404–409 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Azad, S., Sood, N. & Sood, A. Biological and histological parameters as predictors of relapse in ulcerative colitis: a prospective study. Saudi J. Gastroenterol. 17, 194–198 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  41. Feagan, B. G. et al. Treatment of ulcerative colitis with a humanized antibody to the α4β7 integrin. N. Engl. J. Med. 352, 2499–2507 (2005).

    Article  CAS  PubMed  Google Scholar 

  42. Panes, J. et al. Imaging techniques for assessment of inflammatory bowel disease: joint ECCO and ESGAR evidence-based consensus guidelines. J. Crohns Colitis 7, 556–585 (2013).

    Article  CAS  PubMed  Google Scholar 

  43. Benchimol, E. I. et al. Toxic megacolon in children with inflammatory bowel disease: clinical and radiographic characteristics. Am. J. Gastroenterol. 103, 1524–1531 (2008).

    Article  PubMed  Google Scholar 

  44. Allison, M. C. & Vallance, R. Prevalence of proximal faecal stasis in active ulcerative colitis. Gut 32, 179–182 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Fletcher, J. G., Fidler, J. L., Bruining, D. H. & Huprich, J. E. New concepts in intestinal imaging for inflammatory bowel diseases. Gastroenterology 140, 1795–1806 (2011).

    Article  PubMed  Google Scholar 

  46. Yarur, A. J. et al. Predictive factors for clinically actionable computed tomography findings in inflammatory bowel disease patients seen in the emergency department with acute gastrointestinal symptoms. J. Crohns Colitis 8, 504–512 (2014).

    Article  PubMed  Google Scholar 

  47. Ordas, I. et al. Diagnostic accuracy of magnetic resonance colonography for the evaluation of disease activity and severity in ulcerative colitis: a prospective study. Gut 62, 1566–1572 (2013).

    Article  PubMed  Google Scholar 

  48. Oussalah, A. et al. Diffusion-weighted magnetic resonance without bowel preparation for detecting colonic inflammation in inflammatory bowel disease. Gut 59, 1056–1065 (2010).

    Article  PubMed  Google Scholar 

  49. Parente, F. et al. Are colonoscopy and bowel ultrasound useful for assessing response to short-term therapy and predicting disease outcome of moderate-to-severe forms of ulcerative colitis?: a prospective study. Am. J. Gastroenterol. 105, 1150–1157 (2010).

    Article  PubMed  Google Scholar 

  50. Parente, F. A. et al. Response to high-dose steroids of severe attacks of ulcerative colitis may rely on bowel ultrasound instead of colonoscopy: a preliminary study. Gut 55 A118 (2006).

    Google Scholar 

  51. Asthana, A. K. et al. Failure of gastroenterologists to apply intestinal ultrasound in inflammatory bowel disease in the Asia-Pacific: a need for action. J. Gastroenterol. Hepatol. 30, 446–452 (2015).

    Article  PubMed  Google Scholar 

  52. Solem, C. A. et al. Correlation of C-reactive protein with clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease. Inflamm. Bowel Dis. 11, 707–712 (2005).

    Article  PubMed  Google Scholar 

  53. Osada, T. et al. Correlations among total colonoscopic findings, clinical symptoms, and laboratory markers in ulcerative colitis. J. Gastroenterol. Hepatol. 23 (Suppl. 2), S262–S267 (2008).

    Article  PubMed  Google Scholar 

  54. Turner, D. et al. Severe pediatric ulcerative colitis: a prospective multicenter study of outcomes and predictors of response. Gastroenterology 138, 2282–2291 (2010).

    Article  CAS  PubMed  Google Scholar 

  55. Travis, S. P. et al. Predicting outcome in severe ulcerative colitis. Gut 38, 905–910 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Kumar, S., Ghoshal, U. C., Aggarwal, R., Saraswat, V. A. & Choudhuri, G. Severe ulcerative colitis: prospective study of parameters determining outcome. J. Gastroenterol. Hepatol. 19, 1247–1252 (2004).

    Article  PubMed  Google Scholar 

  57. Aceituno, M. et al. Steroid-refractory ulcerative colitis: predictive factors of response to cyclosporine and validation in an independent cohort. Inflamm. Bowel Dis. 14, 347–352 (2008).

    Article  PubMed  Google Scholar 

  58. Cesarini, M. C. et al. P079. Predicting the risk of acute severe colitis (ASC) at diagnosis of Ulcerative Colitis (UC): external validation. J. Crohns Colitis 9 (Suppl. 1), S117–118 (2015).

    Google Scholar 

  59. Henriksen, M. et al. C-Reactive protein: a predictive factor and marker of inflammation in inflammatory bowel disease. Results from a prospective population-based study. Gut 57, 1518–1523 (2008).

    Article  CAS  PubMed  Google Scholar 

  60. Yoon, J. Y. et al. Correlations of C-reactive protein levels and erythrocyte sedimentation rates with endoscopic activity indices in patients with ulcerative colitis. Dig. Dis. Sci. 59, 829–837 (2014).

    Article  CAS  PubMed  Google Scholar 

  61. Guardiola, J. et al. Fecal level of calprotectin identifies histologic inflammation in patients with ulcerative colitis in clinical and endoscopic remission. Clin. Gastroenterol. Hepatol. 12, 1865–1870 (2014).

    Article  CAS  PubMed  Google Scholar 

  62. Yamaguchi, S. et al. Fecal calprotectin is a clinically relevant biomarker of mucosal healing in patients with quiescent ulcerative colitis. J. Gastroenterol. Hepatol. 31, 93–98 (2016).

    Article  CAS  PubMed  Google Scholar 

  63. Theede, K. et al. Level of fecal calprotectin correlates with endoscopic and histologic inflammation and identifies patients with mucosal healing in ulcerative colitis. Clin. Gastroenterol. Hepatol. 13, 1929–1936.e1 (2015).

    Article  CAS  PubMed  Google Scholar 

  64. Yamamoto, T., Shiraki, M., Bamba, T., Umegae, S. & Matsumoto, K. Fecal calprotectin and lactoferrin as predictors of relapse in patients with quiescent ulcerative colitis during maintenance therapy. Int. J. Colorectal Dis. 29, 485–491 (2014).

    Article  PubMed  Google Scholar 

  65. Gisbert, J. P. et al. Fecal calprotectin and lactoferrin for the prediction of inflammatory bowel disease relapse. Inflamm. Bowel Dis. 15, 1190–1198 (2009).

    Article  PubMed  Google Scholar 

  66. De Vos, M. et al. Consecutive fecal calprotectin measurements to predict relapse in patients with ulcerative colitis receiving infliximab maintenance therapy. Inflamm. Bowel Dis. 19, 2111–2117 (2013).

    Article  PubMed  Google Scholar 

  67. Molander, P. et al. Fecal calprotectin concentration predicts outcome in inflammatory bowel disease after induction therapy with TNFalpha blocking agents. Inflamm. Bowel Dis. 18, 2011–2017 (2012).

    Article  PubMed  Google Scholar 

  68. Molander, P. et al. Does fecal calprotectin predict short-term relapse after stopping TNFα-blocking agents in inflammatory bowel disease patients in deep remission? J. Crohns Colitis 9, 33–40 (2015).

    PubMed  Google Scholar 

  69. Osterman, M. T. et al. Mesalamine dose escalation reduces fecal calprotectin in patients with quiescent ulcerative colitis. Clin. Gastroenterol. Hepatol. 12, 1887–1893.e3 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Falvey, J. D. et al. Disease activity assessment in IBD: clinical indices and biomarkers fail to predict endoscopic remission. Inflamm. Bowel Dis. 21, 824–831 (2015).

    Article  PubMed  Google Scholar 

  71. Mosli, M. H. et al. C-Reactive protein, fecal calprotectin, and stool lactoferrin for detection of endoscopic activity in symptomatic inflammatory bowel disease patients: a systematic review and meta-analysis. Am. J. Gastroenterol. 110, 802–819 (2015).

    Article  PubMed  Google Scholar 

  72. Calafat, M. et al. High within-day variability of fecal calprotectin levels in patients with active ulcerative colitis: what is the best timing for stool sampling? Inflamm. Bowel Dis. 21, 1072–1076 (2015).

    Article  PubMed  Google Scholar 

  73. Kristensen, V. et al. Prediction of endoscopic disease activity in ulcerative colitis by two different assays for fecal calprotectin. J. Crohns Colitis 9, 164–169 (2015).

    Article  PubMed  Google Scholar 

  74. Porter, M. E. What is value in health care? N. Engl. J. Med. 363, 2477–2481 (2010).

    Article  CAS  PubMed  Google Scholar 

  75. Guyatt, G. et al. A new measure of health status for clinical trials in inflammatory bowel disease. Gastroenterology 96, 804–810 (1989).

    Article  CAS  PubMed  Google Scholar 

  76. Bodger, K., Ormerod, C., Shackcloth, D. & Harrison, M. Development and validation of a rapid, generic measure of disease control from the patient's perspective: the IBD-control questionnaire. Gut 63, 1092–1102 (2014).

    Article  PubMed  Google Scholar 

  77. Irvine, E. J., Zhou, Q. & Thompson, A. K. The Short Inflammatory Bowel Disease Questionnaire: a quality of life instrument for community physicians managing inflammatory bowel disease. CCRPT Investigators. Canadian Crohn's Relapse Prevention Trial. Am. J. Gastroenterol. 91, 1571–1578 (1996).

    CAS  PubMed  Google Scholar 

  78. Alrubaiy, L. et al. Development of a short questionnaire to assess the quality of life in Crohn's disease and ulcerative colitis. J. Crohns Colitis 9, 66–76 (2015).

    Article  PubMed  Google Scholar 

  79. Jowett, S. L., Seal, C. J., Barton, J. R. & Welfare, M. R. The short inflammatory bowel disease questionnaire is reliable and responsive to clinically important change in ulcerative colitis. Am. J. Gastroenterol. 96, 2921–2928 (2001).

    Article  CAS  PubMed  Google Scholar 

  80. Seagrove, A. C. et al. Randomised controlled trial. Comparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis: Trial design and protocol (CONSTRUCT). BMJ Open 4, e005091 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  81. Best, W. R., Becktel, J. M., Singleton, J. W. & Kern, F. Jr. Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study. Gastroenterology 70, 439–444 (1976).

    Article  CAS  PubMed  Google Scholar 

  82. Sands, B. E. & Ooi, C. J. A survey of methodological variation in the Crohn's disease activity index. Inflamm. Bowel Dis. 11, 133–138 (2005).

    Article  PubMed  Google Scholar 

  83. Harvey, R. F. & Bradshaw, J. M. A simple index of Crohn's-disease activity. Lancet 1, 514 (1980).

    Article  CAS  PubMed  Google Scholar 

  84. Vermeire, S., Schreiber, S., Sandborn, W. J., Dubois, C. & Rutgeerts, P. Correlation between the Crohn's disease activity and Harvey-Bradshaw indices in assessing Crohn's disease severity. Clin. Gastroenterol. Hepatol. 8, 357–363 (2010).

    Article  PubMed  Google Scholar 

  85. Irvine, E. J. Usual therapy improves perianal Crohn's disease as measured by a new disease activity index. McMaster IBD Study group. J. Clin. Gastroenterol. 20, 27–32 (1995).

    Article  CAS  PubMed  Google Scholar 

  86. D'Haens, G. R. et al. Endpoints for clinical trials evaluating disease modification and structural damage in adults with Crohn's disease. Inflamm. Bowel Dis. 15, 1599–1604 (2009).

    Article  PubMed  Google Scholar 

  87. De Cruz, P., Kamm, M. A., Prideaux, L., Allen, P. B. & Moore, G. Mucosal healing in Crohn's disease: a systematic review. Inflamm. Bowel Dis. 19, 429–444 (2013).

    Article  PubMed  Google Scholar 

  88. Mary, J. Y. & Modigliani, R. Development and validation of an endoscopic index of the severity for Crohn's disease: a prospective multicentre study. Groupe d'Etudes Therapeutiques des Affections Inflammatoires du Tube Digestif (GETAID). Gut 30, 983–989 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Daperno, M. et al. Development and validation of a new, simplified endoscopic activity score for Crohn's disease: the SES-CD. Gastrointest. Endosc. 60, 505–512 (2004).

    Article  PubMed  Google Scholar 

  90. Rutgeerts, P. et al. Predictability of the postoperative course of Crohn's disease. Gastroenterology 99, 956–963 (1990).

    Article  CAS  PubMed  Google Scholar 

  91. Rutgeerts, P. et al. Natural history of recurrent Crohn's disease at the ileocolonic anastomosis after curative surgery. Gut 25, 665–672 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. D'Haens, G. R. et al. Early lesions of recurrent Crohn's disease caused by infusion of intestinal contents in excluded ileum. Gastroenterology 114, 262–267 (1998).

    Article  CAS  PubMed  Google Scholar 

  93. Korelitz, B. I. & Sommers, S. C. Response to drug therapy in Crohn's disease: evaluation by rectal biopsy and mucosal cell counts. J. Clin. Gastroenterol. 6, 123–127 (1984).

    Article  CAS  PubMed  Google Scholar 

  94. Molander, P. et al. Achievement of deep remission during scheduled maintenance therapy with TNFα-blocking agents in IBD. J. Crohns Colitis 7, 730–735 (2013).

    Article  PubMed  Google Scholar 

  95. D'Haens, G. et al. Endoscopic and histological healing with infliximab anti-tumor necrosis factor antibodies in Crohn's disease: a European multicenter trial. Gastroenterology 116, 1029–1034 (1999).

    Article  CAS  PubMed  Google Scholar 

  96. Geboes, K. et al. Endoscopic and histologic evidence of persistent mucosal healing and correlation with clinical improvement following sustained infliximab treatment for Crohn's disease. Curr. Med. Res. Opin. 21, 1741–1754 (2005).

    Article  CAS  PubMed  Google Scholar 

  97. Panes, J. et al. Systematic review: the use of ultrasonography, computed tomography and magnetic resonance imaging for the diagnosis, assessment of activity and abdominal complications of Crohn's disease. Aliment. Pharmacol. Ther. 34, 125–145 (2011).

    Article  CAS  PubMed  Google Scholar 

  98. Craig, O. et al. Diagnostic accuracy of computed tomography using lower doses of radiation for patients with Crohn's disease. Clin. Gastroenterol. Hepatol. 10, 886–892 (2012).

    Article  PubMed  Google Scholar 

  99. Kuehle, C. A. et al. Hydro-MRI of the small bowel: effect of contrast volume, timing of contrast administration, and data acquisition on bowel distention. AJR. Am. J. Roentgenol. 187, W375–385 (2006).

    Article  PubMed  Google Scholar 

  100. Rimola, J. et al. Magnetic resonance imaging for evaluation of Crohn's disease: validation of parameters of severity and quantitative index of activity. Inflamm. Bowel Dis. 17, 1759–1768 (2011).

    Article  PubMed  Google Scholar 

  101. Rimola, J. et al. Magnetic resonance for assessment of disease activity and severity in ileocolonic Crohn's disease. Gut 58, 1113–1120 (2009).

    Article  CAS  PubMed  Google Scholar 

  102. Ordas, I. et al. Accuracy of magnetic resonance enterography in assessing response to therapy and mucosal healing in patients with Crohn's disease. Gastroenterology 146, 374–382.e1 (2014).

    Article  CAS  PubMed  Google Scholar 

  103. Cipriano, L. E., Levesque, B. G., Zaric, G. S., Loftus, E. V. Jr & Sandborn, W. J. Cost-effectiveness of imaging strategies to reduce radiation-induced cancer risk in Crohn's disease. Inflamm. Bowel Dis. 18, 1240–1248 (2012).

    Article  PubMed  Google Scholar 

  104. Van Assche, G. et al. Magnetic resonance imaging of the effects of infliximab on perianal fistulizing Crohn's disease. Am. J. Gastroenterol. 98, 332–339 (2003).

    Article  PubMed  Google Scholar 

  105. Parks, A. G., Gordon, P. H. & Hardcastle, J. D. A classification of fistula-in-ano. Br. J. Surg. 63, 1–12 (1976).

    Article  CAS  PubMed  Google Scholar 

  106. Martinez, M. J., Ripolles, T., Paredes, J. M., Blanc, E. & Marti-Bonmati, L. Assessment of the extension and the inflammatory activity in Crohn's disease: comparison of ultrasound and MRI. Abdom. Imag. 34, 141–148 (2009).

    Article  Google Scholar 

  107. Migaleddu, V. et al. Contrast-enhanced ultrasonographic evaluation of inflammatory activity in Crohn's disease. Gastroenterology 137, 43–52 (2009).

    Article  PubMed  Google Scholar 

  108. Neye, H. et al. Evaluation of criteria for the activity of Crohn's disease by power Doppler sonography. Dig. Dis. (Basel, Switzerland) 22, 67–72 (2004).

    Article  PubMed  Google Scholar 

  109. Limberg, B. Diagnosis of chronic inflammatory bowel disease by ultrasonography. Zeitschrift Gastroenterol. 37, 495–508 (1999).

    CAS  Google Scholar 

  110. Paredes, J. M. et al. Abdominal sonographic changes after antibody to tumor necrosis factor (anti-TNF) alpha therapy in Crohn's Disease. Dig. Dis. Sci. 55, 404–410 (2010).

    Article  CAS  PubMed  Google Scholar 

  111. Calabrese, E. et al. Development of a numerical index quantitating small bowel damage as detected by ultrasonography in Crohn's disease. J. Crohns Colitis 6, 852–860 (2012).

    Article  PubMed  Google Scholar 

  112. Moreno, N. et al. Usefulness of abdominal ultrasonography in the analysis of endoscopic activity in patients with Crohn's disease: changes following treatment with immunomodulators and/or anti-TNF antibodies. J. Crohns Colitis 8, 1079–1087 (2014).

    Article  PubMed  Google Scholar 

  113. Zorzi, F. et al. A sonographic lesion index for Crohn's disease helps monitor changes in transmural bowel damage during therapy. Clin. Gastroenterol. Hepatol. 12, 2071–2077 (2014).

    Article  PubMed  Google Scholar 

  114. Calabrese, E. et al. Accuracy of small-intestine contrast ultrasonography, compared with computed tomography enteroclysis, in characterizing lesions in patients with Crohn's disease. Clin. Gastroenterol. Hepatol. 11, 950–955 (2013).

    Article  PubMed  Google Scholar 

  115. Castiglione, F. et al. Oral contrast-enhanced sonography for the diagnosis and grading of postsurgical recurrence of Crohn's disease. Inflamm. Bowel Dis. 14, 1240–1245 (2008).

    Article  PubMed  Google Scholar 

  116. Novak, K. et al. Clinic-based Point of Care Transabdominal Ultrasound for Monitoring Crohn's Disease: Impact on Clinical Decision Making. J. Crohns Colitis 9, 795–801 (2015).

    Article  PubMed  Google Scholar 

  117. Kiss, L. S. et al. Early clinical remission and normalisation of CRP are the strongest predictors of efficacy, mucosal healing and dose escalation during the first year of adalimumab therapy in Crohn's disease. Aliment. Pharmacol. Ther. 34, 911–922 (2011).

    Article  CAS  PubMed  Google Scholar 

  118. Hanauer, S. B. et al. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn's disease: the CLASSIC-I trial. Gastroenterology 130, 323–333 (2006).

    Article  CAS  PubMed  Google Scholar 

  119. Lamireau, T. et al. Efficacy and tolerance of infliximab in children and adolescents with Crohn's disease. Inflamm. Bowel Dis. 10, 745–750 (2004).

    Article  PubMed  Google Scholar 

  120. Rutgeerts, P. et al. Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn's disease. Gastroenterology 117, 761–769 (1999).

    Article  CAS  PubMed  Google Scholar 

  121. Targan, S. R. et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group. N. Engl. J. Med. 337, 1029–1035 (1997).

    Article  CAS  PubMed  Google Scholar 

  122. Reinisch, W. et al. Factors associated with short- and long-term outcomes of therapy for Crohn's disease. Clin. Gastroenterol. Hepatol. 13, 539–547.e2 (2015).

    Article  PubMed  Google Scholar 

  123. Sipponen, T. et al. Faecal calprotectin and lactoferrin are reliable surrogate markers of endoscopic response during Crohn's disease treatment. Scand. J. Gastroenterol. 45, 325–331 (2010).

    Article  CAS  PubMed  Google Scholar 

  124. Kiss, L. S. et al. High-sensitivity C-reactive protein for identification of disease phenotype, active disease, and clinical relapses in Crohn's disease: a marker for patient classification? Inflamm. Bowel Dis. 18, 1647–1654 (2012).

    Article  PubMed  Google Scholar 

  125. Henderson, P. et al. Serum C-reactive protein and CRP genotype in pediatric inflammatory bowel disease: influence on phenotype, natural history, and response to therapy. Inflamm. Bowel Dis. 21, 596–605 (2015).

    Article  PubMed  Google Scholar 

  126. Click, B. et al. Silent crohn's disease: asymptomatic patients with elevated C-reactive protein are at risk for subsequent hospitalization. Inflamm. Bowel Dis. 21, 2254–2261 (2015).

    PubMed  Google Scholar 

  127. Kennedy, N. A. et al. Thiopurine withdrawal during sustained clinical remission in inflammatory bowel disease: relapse and recapture rates, with predictive factors in 237 patients. Aliment. Pharmacol. Ther. 40, 1313–1323 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Louis, E. et al. Maintenance of remission among patients with Crohn's disease on antimetabolite therapy after infliximab therapy is stopped. Gastroenterology 142, 63–70 e65 (2012).

    Article  CAS  PubMed  Google Scholar 

  129. Treton, X. et al. Azathioprine withdrawal in patients with Crohn's disease maintained on prolonged remission: a high risk of relapse. Clin. Gastroenterol. Hepatol. 7, 80–85 (2009).

    Article  PubMed  Google Scholar 

  130. Reinisch, W., Wang, Y., Oddens, B. J. & Link, R. C-Reactive protein, an indicator for maintained response or remission to infliximab in patients with Crohn's disease: a post-hoc analysis from ACCENT I. Aliment. Pharmacol. Ther. 35, 568–576 (2012).

    Article  CAS  PubMed  Google Scholar 

  131. Jones, J. et al. Relationships between disease activity and serum and fecal biomarkers in patients with Crohn's disease. Clin. Gastroenterol. Hepatol. 6, 1218–1224 (2008).

    Article  PubMed  Google Scholar 

  132. Zubin, G. & Peter, L. Predicting endoscopic crohn's disease activity before and after induction therapy in children: a comprehensive assessment of PCDAI, CRP, and fecal calprotectin. Inflamm. Bowel Dis. 21, 1386–1391 (2015).

    PubMed  PubMed Central  Google Scholar 

  133. Chamouard, P., Richert, Z., Meyer, N., Rahmi, G. & Baumann, R. Diagnostic value of C-reactive protein for predicting activity level of Crohn's disease. Clin. Gastroenterol. Hepatol. 4, 882–887 (2006).

    Article  CAS  PubMed  Google Scholar 

  134. Karoui, S. et al. Correlation between levels of C-reactive protein and clinical activity in Crohn's disease. Dig. Liver Dis. 39, 1006–1010 (2007).

    Article  CAS  PubMed  Google Scholar 

  135. Florin, T. H., Paterson, E. W., Fowler, E. V. & Radford-Smith, G. L. Clinically active Crohn's disease in the presence of a low C-reactive protein. Scand. J. Gastroenterol. 41, 306–311 (2006).

    Article  CAS  PubMed  Google Scholar 

  136. Yang, D. H. et al. Usefulness of C-reactive protein as a disease activity marker in Crohn's disease according to the location of disease. Gut Liver 9, 80–86 (2015).

    Article  CAS  PubMed  Google Scholar 

  137. Wright, E. K. et al. Measurement of fecal calprotectin improves monitoring and detection of recurrence of Crohn's disease after surgery. Gastroenterology 148, 938–947 (2015).

    Article  CAS  PubMed  Google Scholar 

  138. Cerrillo, E. et al. Fecal calprotectin in ileal Crohn's disease: relationship with magnetic resonance enterography and a pathology score. Inflamm. Bowel Dis. 21, 1572–1579 (2015).

    Article  PubMed  Google Scholar 

  139. Schoepfer, A. M. et al. Fecal calprotectin more accurately reflects endoscopic activity of ulcerative colitis than the Lichtiger Index, C-reactive protein, platelets, hemoglobin, and blood leukocytes. Inflamm. Bowel Dis. 19, 332–341 (2013).

    Article  PubMed  Google Scholar 

  140. D'Haens, G. et al. Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease. Inflamm. Bowel Dis. 18, 2218–2224 (2012).

    Article  PubMed  Google Scholar 

  141. Ferreiro-Iglesias, R. et al. Fecal calprotectin as predictor of relapse in patients with inflammatory bowel disease under maintenance infliximab therapy. J. Clin. Gastroenterol. 50, 147–151 (2016).

    Article  CAS  PubMed  Google Scholar 

  142. Mooiweer, E. et al. Low fecal calprotectin predicts sustained clinical remission in inflammatory bowel disease patients: a plea for deep remission. J. Crohns Colitis 9, 50–55 (2015).

    Article  PubMed  Google Scholar 

  143. De Cruz, P. et al. Postoperative recurrence of Crohn's disease: impact of endoscopic monitoring and treatment step-up. Colorectal Dis. 15, 187–197 (2013).

    Article  CAS  PubMed  Google Scholar 

  144. Gecse, K. B. et al. Impact of disease location on fecal calprotectin levels in Crohn's disease. Scand. J. Gastroenterol. 50, 841–847 (2015).

    Article  CAS  PubMed  Google Scholar 

  145. Allen, P. B. & Peyrin-Biroulet, L. Moving towards disease modification in inflammatory bowel disease therapy. Curr. Opin. Gastroenterol. 29, 397–404 (2013).

    Article  CAS  PubMed  Google Scholar 

  146. Peyrin-Biroulet, L. et al. Defining disease severity in inflammatory bowel disease: current and future directions. Clin. Gastroenterol. Hepatol. 14, 348–354.e17 (2016).

    Article  PubMed  Google Scholar 

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Author notes

  1. Alissa J. Walsh and Robert V. Bryant: These authors are joint first authors.

Authors and Affiliations

  1. Experimental Medicine Division, Translational Gastroenterology Unit, John Radcliffe Hospital, Headley Way, Headington, OX3 9DU, Oxford, UK

    Alissa J. Walsh & Simon P. L. Travis

  2. Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, North Terrace, Adelaide, 5000, South Australia, Australia

    Robert V. Bryant

  3. School of Medicine, University of Adelaide, Adelaide, 5005, South Australia, Australia

    Robert V. Bryant

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All authors contributed equally to this article.

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Correspondence to Alissa J. Walsh.

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Competing interests

A.J.W. has served as an advisory board member for AbbVie, Ferring, Janssen-Cilag, Hospira and Takeda. She has received honoraria for speaking from AbbVie, Ferring, Janssen-Cilag and Shire, and has received grants for support of research from AbbVie, Ferring, Janssen-Cilag and Shire. R.V.B. has received conference attendance support from Ferring, Janssen, and Takeda, and honoraria for speaking from Abbvie, Janssen-Cilag and Shire, and S.P.L.T. has received grants for research support from AbbVie, Lilly, Norman Collison Foundation, UCB and Vifor. He has received consulting and/or speaker fees from AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Cosmo, Ferring, Giuliani SpA, GlaxoSmithKline, Lilly, MSD, Neovacs, Novartis, Norman Collison Foundation, Novo Nordisk, Pfizer, Proximagen, Receptos, Shire, Sigmoid Pharma, Takeda, TopiVert, UCB, VHsquared, Vifor, and Warner Chilcott.

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FURTHER INFORMATION

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Supplementary information

Supplementary information S1 (tables)

List of disease activity indices for ulcerative colitis (PDF 281 kb)

Supplementary information S2 (tables)

Simple Clinical Colitis Activity Index (SCCAI) (PDF 656 kb)

Supplementary information S3 (box 1)

Search methodology (PDF 104 kb)

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Walsh, A., Bryant, R. & Travis, S. Current best practice for disease activity assessment in IBD. Nat Rev Gastroenterol Hepatol 13, 567–579 (2016). https://doi.org/10.1038/nrgastro.2016.128

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