Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

State-of-the-art medical prevention of postoperative recurrence of Crohn's disease

Nature Reviews Gastroenterology & Hepatology volume 10, pages 413–422 (2013)Cite this article

Subjects

This article has been updated

Abstract

Postoperative recurrence of Crohn's disease is a frequent and often severe sequela of the disease. Until a few years ago it was deemed inescapable, as all the conventional medications used to treat the disease have been proven of little benefit in preventing recurrence after surgical treatment. In the past few years, anti-TNF agents given immediately after surgery have shown a remarkable efficacy in the prevention of disease recurrence. Large, randomized, controlled trials are currently underway to confirm these findings. Anti-TNF treatment of endoscopic lesions that occur after surgery seems to be less effective than using TNF antagonists to prevent recurrence. However, although the data are limited, this treatment strategy seems to be still superior to all the other prevention strategies that are not based on anti-TNF agents. Limited data are available on long-term outcomes of patients treated with anti-TNF agents after surgery. They suggest that these medications are safe and effective after many years of treatment. In addition, these agents might prevent recurrence even at doses lower than those used in patients with Crohn's disease who have not had surgery.

Key Points

  • Recurrence of Crohn's disease after surgery is frequent and often severe

  • Existing medications used to treat patients with Crohn's disease, such as mesalazine, antibiotics and immunomodulators, have proven of little benefit for this indication

  • In recent years, a number of studies have shown anti-TNF agents to be extremely effective, either given preventively immediately after surgery or to treat mucosal recurrence that has already taken place

  • Large randomized studies are seeking to confirm these findings

  • Current, albeit limited, evidence indicates that anti-TNF agents might be effective in the long term, even at doses lower than those used in patients who have not had surgery

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Ileocolic anastomosis after infliximab interruption and re-treatment with low doses.
Figure 2: Proposed algorithm to prevent postoperative recurrence in patients at low and high risk of recurrence after ileocolonic resection.

Similar content being viewed by others

Change history

  • 09 May 2013

    In the version of this article initially published online, the year of publication of reference 95 in Table 2 was incorrect. The error has been corrected for the print, HTML and PDF versions of the article.

References

  1. 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 

  2. Sorrentino, D. & Paviotti, A. Postsurgical recurrence of Crohn's disease: the beginning of the end? Gastroenterology 137, 1181–1182 (2009).

    Article  PubMed  Google Scholar 

  3. Regueiro, M. et al. Crohn's disease activity index does not correlate with endoscopic recurrence one year after ileocolonic resection. Inflamm. Bowel Dis. 17, 118–126 (2011).

    Article  PubMed  Google Scholar 

  4. Hanauer, S. B. et al. Postoperative maintenance of Crohn's disease remission with 6-mercaptopurine, mesalamine, or placebo: a 2-year trial. Gastroenterology 127, 723–729 (2004).

    Article  CAS  PubMed  Google Scholar 

  5. Sorrentino, D., Terrosu, G., Avellini, A. & Maiero, S. Infliximab and low dose methotrexate for prevention of postsurgical recurrence of ileocolonic Crohn's disease. Arch. Intern. Med. 167, 1804–1810 (2007).

    Article  PubMed  Google Scholar 

  6. Walters, T. D. et al. Validating Crohn's disease activity indices for use in assessing postoperative recurrence. Inflamm. Bowel Dis. 17, 1547–1556 (2011).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  8. Sachar, D. B. Recurrence rates in Crohn's disease: predicting the future and predicting the past. Gut 55, 1069–1070 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Terdiman, J. P. Prevention of postoperative recurrence in Crohn's disease. Clin. Gastroenterol. Hepatol. 6, 616–620 (2008).

    Article  PubMed  Google Scholar 

  10. Lamb, C. A. et al. Faecal calprotectin or lactoferrin can identify postoperative recurrence in Crohn's disease. Br. J. Surg. 96, 663–674 (2009).

    Article  CAS  PubMed  Google Scholar 

  11. Sorrentino, D. et al. Early diagnosis and treatment of postoperative endoscopic recurrence of Crohn's disease: partial benefit by infliximab-a pilot study. Dig. Dis. Sci. 57, 1341–1348 (2012).

    Article  CAS  PubMed  Google Scholar 

  12. Bourreille, A. et al. Wireless capsule endoscopy versus ileocolonoscopy for the diagnosis of postoperative recurrence of Crohn's disease: a prospective study. Gut 55, 978–983 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Koilakou, S. et al. Endoscopy and MR enteroclysis: equivalent tools in predicting clinical recurrence in patients with Crohn's disease after ileocolic resection. Inflamm. Bowel Dis. 16, 198–203 (2010).

    Article  PubMed  Google Scholar 

  14. Soyer, P. et al. Suspected anastomotic recurrence of Crohn disease after ileocolic resection: evaluation with CT enteroclysis. Radiology 254, 755–764 (2010).

    Article  PubMed  Google Scholar 

  15. 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 

  16. Sachar, D. B. et al. Recurrence patterns after first resection for stricturing or penetrating Crohn's disease. Inflamm. Bowel Dis. 15, 1071–1075 (2009).

    Article  PubMed  Google Scholar 

  17. Watanabe, T. et al. Interval of less than 5 years between the first and second operation is a risk factor for a third operation for Crohn's disease. Inflamm. Bowel Dis. 18, 17–24 (2012).

    Article  PubMed  Google Scholar 

  18. Buisson, A., Chevaux, J. B., Allen, P. B., Bommelaer, G. & Peyrin-Biroulet, L. The natural history of post-operative Crohn's disease recurrence. Aliment. Pharmacol. Ther. 35, 625–633 (2012).

    Article  CAS  PubMed  Google Scholar 

  19. Ferrante, M. et al. The value of myenteric plexitis to predict early postoperative Crohn's disease recurrence. Gastroenterology 130, 1595–1606 (2006).

    Article  PubMed  Google Scholar 

  20. Ng, S. C. et al. Predictive value and clinical significance of myenteric plexitis in Crohn's disease. Inflamm. Bowel Dis. 15, 1499–1507 (2009).

    Article  PubMed  Google Scholar 

  21. Sokol, H. et al. Plexitis as a predictive factor of early postoperative clinical recurrence in Crohn's disease. Gut 58, 1218–1225 (2009).

    Article  CAS  PubMed  Google Scholar 

  22. Simillis, C., Jacovides, M., Reese, G. E., Yamamoto, T. & Tekkis, P. P. Meta-analysis of the role of granulomas in the recurrence of Crohn disease. Dis. Colon Rectum 53, 177–185 (2010).

    Article  PubMed  Google Scholar 

  23. Bernell, O., Lapidus, A. & Hellers, G. Risk factors for surgery and recurrence in 907 patients with primary ileocaecal Crohn's disease. Br. J. Surg. 87, 1697–1701 (2000).

    Article  CAS  PubMed  Google Scholar 

  24. Yamamoto, T., Allan, R. N. & Keighley, M. R. Long-term outcome of surgical management for diffuse jejunoileal Crohn's disease. Surgery 129, 96–102 (2001).

    Article  CAS  PubMed  Google Scholar 

  25. Poggioli, G. et al. Factors affecting recurrence in Crohn's disease. Results of a prospective audit. Int. J. Colorectal Dis. 11, 294–298 (1996).

    Article  CAS  PubMed  Google Scholar 

  26. De Cruz, P., Kamm, M. A., Prideaux, L., Allen, P. B. & Desmond, P. V. Postoperative recurrent luminal Crohn's disease: a systematic review. Inflamm. Bowel Dis. 18, 758–777 (2012).

    Article  PubMed  Google Scholar 

  27. Reese, G. E. et al. The effect of smoking after surgery for Crohn's disease: a meta-analysis of observational studies. Int. J. Colorectal Dis. 23, 1213–1221 (2008).

    Article  PubMed  Google Scholar 

  28. Yamamoto, T. & Keighley, M. R. Smoking and disease recurrence after operation for Crohn's disease. Br. J. Surg. 87, 398–404 (2000).

    Article  CAS  PubMed  Google Scholar 

  29. Cottone, M. et al. Smoking habits and recurrence in Crohn's disease. Gastroenterology 106, 643–648 (1994).

    Article  CAS  PubMed  Google Scholar 

  30. McLeod, R. S. et al. Risk and significance of endoscopic/radiological evidence of recurrent Crohn's disease. Gastroenterology 113, 1823–1827 (1997).

    Article  CAS  PubMed  Google Scholar 

  31. Scarpa, M. et al. Surgical predictors of recurrence of Crohn's disease after ileocolonic resection. Int. J. Colorectal Dis. 22, 1061–1069 (2007).

    Article  PubMed  Google Scholar 

  32. Maconi, G. et al. CARD15 gene variants and risk of reoperation in Crohn's disease patients. Am. J. Gastroenterol. 104, 2483–2491 (2009).

    Article  CAS  PubMed  Google Scholar 

  33. Caprilli, R. et al. Prognostic factors for postoperative recurrence of Crohn's disease. Gruppo Italiano per lo Studio del Colon e del Retto (GISC). Dis. Colon Rectum 39, 335–341 (1996).

    Article  CAS  PubMed  Google Scholar 

  34. Post, S. et al. The impact of disease pattern, surgical management, and individual surgeons on the risk for relaparotomy for recurrent Crohn's disease. Ann. Surg. 223, 253–260 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kinchen, J., Rajaratnam, K., Kingston, G., Mee, A. S. & De Silva, A. N. The presence of microscopic disease at the resection margins predicts post-surgical relapse in Crohn's Disease. Gastroenterology 142, S1068 (2012).

    Article  Google Scholar 

  36. Fazio, V. W. et al. Effects of resection margin on the recurrence of Crohn's disease in the small bowel: a randomized controlled trial. Ann. Surg. 224, 563–571 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Renna, S. et al. Meta-analysis of the placebo rates of clinical relapse and severe endoscopic recurrence in postoperative Crohn's disease. Gastroenterology 135, 1500–1509 (2008).

    Article  CAS  PubMed  Google Scholar 

  38. McLeod, R. S. et al. Prophylactic mesalamine treatment decreases postoperative recurrence of Crohn's disease. Gastroenterology 109, 404–413 (1995).

    Article  CAS  PubMed  Google Scholar 

  39. Brignola, C. et al. Mesalamine in the prevention of endoscopic recurrence after intestinal resection for Crohn's disease. Italian Cooperative Study Group. Gastroenterology 108, 345–349 (1995).

    Article  CAS  PubMed  Google Scholar 

  40. Sutherland, L. R. et al. A randomized, placebo-controlled, double-blind trial of mesalamine in the maintenance of remission of Crohn's disease. The Canadian Mesalamine for Remission of Crohn's Disease Study Group. Gastroenterology 112, 1069–1077 (1997).

    Article  CAS  PubMed  Google Scholar 

  41. Lochs, H. et al. Prophylaxis of postoperative relapse in Crohn's disease with mesalamine: European Cooperative Crohn's Disease Study VI. Gastroenterology 118, 264–273 (2000).

    Article  CAS  PubMed  Google Scholar 

  42. Caprilli, R. et al. Two mesalazine regimens in the prevention of the post-operative recurrence of Crohn's disease: A pragmatic, double-blind, randomized controlled trial. Aliment. Pharmacol. Ther. 17, 517–523 (2003).

    Article  CAS  PubMed  Google Scholar 

  43. Camma, C., Giunta, M., Rosselli, M. & Cottone, M. Mesalamine in the maintenance treatment of Crohn's disease: A metaanalysis adjusted for confounding variables. Gastroenterology 113, 1465–1473 (1997).

    Article  CAS  PubMed  Google Scholar 

  44. Doherty, G., Bennett, G., Patil, S., Cheifetz, A. & Moss, A. C. Interventions for prevention of post-operative recurrence of Crohn's disease. Cochrane Database of Systematic Reviews, Issue 4. Art. No.: CD006873 http://dx.doi.org/10.1002/14651858.CD006873.pub2 (2009).

  45. Ford, A. C. et al. Efficacy of 5-aminosalicylates in Crohn's disease: systematic review and meta-analysis. Am. J. Gastroenterol. 106, 617–629 (2011).

    Article  CAS  PubMed  Google Scholar 

  46. Ewe, K., Herfarth, C., Malchow, H. & Jesdinsky, H. J. Postoperative recurrence of Crohn's disease in relation to radicality of operation and sulfasalazine prophylaxis: A multicenter trial. Digestion 42, 224–232 (1989).

    Article  CAS  PubMed  Google Scholar 

  47. Ewe, K., Bottger, T., Buhr, H. J., Ecker, K.-W. & Otto, H. F. Low-dose budesonide treatment for prevention of postoperative recurrence of Crohn's disease: a multicentre randomized placebo-controlled trial. German Budesonide Study Group. Eur. J. Gastroenterol. Hepatol. 11, 277–282 (1999).

    Article  CAS  PubMed  Google Scholar 

  48. Hellers, G. et al. Oral budesonide for prevention of postsurgical recurrence in Crohn's disease. The IOIBD Budesonide Study Group. Gastroenterology 116, 294–300 (1999).

    Article  CAS  PubMed  Google Scholar 

  49. Rutgeerts, P. et al. Controlled trial of metronidazole treatment for prevention of Crohn's recurrence after ileal resection. Gastroenterology 108, 1617–1621 (1995).

    Article  CAS  PubMed  Google Scholar 

  50. Rutgeerts, P. et al. Ornidazole for prophylaxis of postoperative Crohn's disease recurrence: a randomized, double-blind, placebo-controlled trial. Gastroenterology 128, 856–861 (2005).

    Article  CAS  PubMed  Google Scholar 

  51. Ardizzone, S. et al. Azathioprine and mesalamine for prevention of relapse after conservative surgery for Crohn's disease. Gastroenterology 127, 730–740 (2004).

    Article  CAS  PubMed  Google Scholar 

  52. Sandborn, W. J. & Feagan, B. G. The efficacy of azathioprine and 6-mercaptopurine for the prevention of postoperative recurrence in patients with Crohn's disease remains uncertain. Gastroenterology 127, 990–993 (2004).

    Article  CAS  PubMed  Google Scholar 

  53. Papay, P. et al. The impact of thiopurines on the risk of surgical recurrence in patients with Crohn's disease after first intestinal surgery. Am. J. Gastroenterol. 105, 1158–1164 (2010).

    Article  CAS  PubMed  Google Scholar 

  54. D'Haens, G. et al. Therapy of metronidazole with azathioprine to prevent postoperative recurrence of Crohn's Disease: a controlled randomized trial. Gastroenterology 135, 1123–1129 (2008).

    Article  CAS  PubMed  Google Scholar 

  55. Herfarth, H. et al. Adverse events in clinical trials with azathioprine and mesalamine for prevention of postoperative recurrence of Crohn's disease. Gut 55, 1525–1526 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Peyrin-Biroulet, L. et al. Azathioprine and 6-mercaptopurine for the prevention of postoperative recurrence in Crohn's disease: a meta-analysis. Am. J. Gastroenterol. 104, 2089–2096 (2009).

    Article  CAS  PubMed  Google Scholar 

  57. Colombel, J. F. et al. Interleukin 10 (Tenovil) in the prevention of postoperative recurrence of Crohn's disease. Gut 49, 42–46 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Esaki, M. et al. Preventive effect of nutritional therapy against postoperative recurrence of Crohn disease, with reference to findings determined by intra-operative enteroscopy. Scand. J. Gastroenterol. 40, 1431–1437 (2005).

    Article  PubMed  Google Scholar 

  59. Yamamoto, T., Nakahigashi, M., Umegae, S., Kitagawa, T. & Matsumoto, K. Impact of long-term enteral nutrition on clinical and endoscopic recurrence after resection for Crohn's disease: a prospective, non-randomized, parallel, controlled study. Aliment. Pharmacol. Ther. 25, 67–72 (2007).

    Article  CAS  PubMed  Google Scholar 

  60. Yamamoto, T., Shiraki, M., Nakahigashi, M., Umegae, S. & Matsumoto, K. Enteral nutrition to suppress postoperative Crohn's disease recurrence: a five-year prospective cohort study. Int. J. Colorectal Dis. 28, 335–340 (2013).

    Article  PubMed  Google Scholar 

  61. Prantera, C., Scribano, M. L., Falasco, G., Andreoli, A. & Luzi, C. Ineffectiveness of probiotics in preventing recurrence after curative resection for Crohn's disease: A randomised controlled trial with Lactobacillus GG. Gut 51, 405–409 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Marteau, P. et al. Ineffectiveness of Lactobacillus johnsonii LA1 for prophylaxis of postoperative recurrence in Crohn's disease: A randomised, double blind, placebo controlled GETAID trial. Gut 55, 842–847 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Van Gossum, A. et al. Multicenter randomized controlled clinical trial of probiotics (Lactobacillus johnsonii, LA1) on early endoscopic recurrence of Crohn's disease after lleo-caecal resection. Inflamm. Bowel Dis. 13, 135–142 (2007).

    Article  PubMed  Google Scholar 

  64. Chermesh, I. et al. Failure of Synbiotic 2000 to prevent postoperative recurrence of Crohn's disease. Dig. Dis. Sci. 52, 385–389 (2007).

    Article  PubMed  Google Scholar 

  65. Rutgeerts, P. et al. Effect of fecal stream diversion on recurrence of Crohn's disease in the neoterminal ileum. Lancet 338, 771–774 (1991).

    Article  CAS  PubMed  Google Scholar 

  66. D'Haens, G. 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 

  67. Fichera, A., McCormack, R., Rubin, M. A., Hurst, R. D. & Michelassi, F. Long-term outcome of surgically treated Crohn's colitis: a prospective study. Dis. Colon Rectum 48, 963–969 (2005).

    Article  PubMed  Google Scholar 

  68. Amiot, A. et al. Crohn's disease recurrence after total proctocolectomy with definitive ileostomy. Dig. Liver Dis. 43, 698–702 (2011).

    Article  PubMed  Google Scholar 

  69. Colombel, J. F. et al. Infliximab, azathioprine, or combination therapy for Crohn's disease. N. Engl. J. Med. 362, 1383–1395 (2010).

    Article  CAS  PubMed  Google Scholar 

  70. D'Haens, G. et al. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial. Lancet 371, 660–667 (2008).

    Article  CAS  PubMed  Google Scholar 

  71. Hanauer, S. B. et al. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet 359, 1541–1549 (2002).

    Article  CAS  PubMed  Google Scholar 

  72. Hyams, J. et al. Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn's disease in children. Gastroenterology 132, 863–873 (2007).

    Article  CAS  PubMed  Google Scholar 

  73. Peyrin-Biroulet, L., Bigard, M. A., Malesci, A. & Danese, S. Step-up and top-down approaches to the treatment of Crohn's disease: early may already be too late. Gastroenterology 135, 1420–1422 (2008).

    Article  PubMed  Google Scholar 

  74. Colombel, J. F. et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial. Gastroenterology 132, 52–65 (2007).

    Article  CAS  PubMed  Google Scholar 

  75. Schreiber, S. et al. Increased response and remission rates in short duration Crohn's disease with subcutaneous certolizumab pegol: an analysis of PRECISE 2 randomized maintenance trial data. Am. J. Gastroenterol. 105, 1574–1582 (2010).

    Article  CAS  PubMed  Google Scholar 

  76. Sorrentino, D. et al. Prevention of postoperative recurrence of Crohn's disease by Infliximab. Eur. J. Gastroenterol. Hepatol. 18, 457–459 (2006).

    Article  PubMed  Google Scholar 

  77. Baert, F. et al. Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease. N. Engl. J. Med. 348, 601–608 (2003).

    Article  CAS  PubMed  Google Scholar 

  78. Sorrentino, D. et al. Low-dose maintenance therapy with infliximab prevents postsurgical recurrence of Crohn's disease. Clin. Gastroenterol. Hepatol. 8, 591–599 (2010).

    Article  CAS  PubMed  Google Scholar 

  79. Hanauer, S. B. Risks and benefits of combining immunosuppressives and biological agents in inflammatory bowel disease: is the synergy worth the risk? Gut 56, 1181–1183 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Regueiro, M. et al. Infliximab prevents Crohn's disease recurrence after ileal resection. Gastroenterology 136, 441–450 (2009).

    Article  CAS  PubMed  Google Scholar 

  81. 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 

  82. Sorrentino, D. Mucosal healing and clinical remission in inflammatory bowel diseases: Are we missing something here? Inflamm. Bowel Dis. 19, E55–E56 (2013).

    Article  PubMed  Google Scholar 

  83. Yoshida, K. et al. Scheduled infliximab monotherapy to prevent recurrence of Crohn's disease following ileocolic or ileal resection: a 3-year prospective randomized open trial. Inflamm. Bowel Dis. 18, 1617–1623 (2012).

    Article  PubMed  Google Scholar 

  84. Sakuraba, A. et al. The use of infliximab in the prevention of postsurgical recurrence in polysurgery Crohn's disease patients: a pilot, open-labeled prospective study. Int. J. Colorectal Dis. 27, 947–952 (2012).

    Article  PubMed  Google Scholar 

  85. Tarekegn, S. et al. Biologics are superior to immunomodulators in prevention of post-operative recurrence of Crohn's disease. Gastroenterology 140, S-592 (2011).

    Article  Google Scholar 

  86. Papamichael, K., Archavlis, E., Lariou, C. & Mantzaris, G. J. Adalimumab for the prevention and/or treatment of post-operative recurrence of Crohn's disease: A prospective, two-year, single center, pilot study. J. Crohns Colitis 6, 924–931 (2012).

    Article  PubMed  Google Scholar 

  87. Savarino, E., Dulbecco, P., Bodini, G., Assandri, L. & Savarino, V. Prevention of postoperative recurrence of Crohn's disease by Adalimumab: a case series. Eur. J. Gastroenterol. Hepatol. 24, 468–470 (2012).

    Article  PubMed  Google Scholar 

  88. Aguas, M. et al. Adalimumab in prevention of postoperative recurrence of Crohn's disease in high-risk patients. World J. Gastroenterol. 18, 4391–4398 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Fernandez-Blanco, I., Monturiol, J. & Martinez, B. Adalimumab in the prevention of postoperative recurrence of Crohn's disease. Gastroenterology 138, S692 (2010).

    Google Scholar 

  90. De Cruz, P. et al. Adalimumab prevents post-operative Crohn's disease recurrence, and is superior to thiopurines: early results from the POCER Study. Gastroenterology 142, S212 (2012).

    Article  Google Scholar 

  91. Hellers, G. Crohn's disease in Stockholm county 1955–1974 A study of epidemiology, results of surgical treatment and long-term prognosis. Acta Chir. Scand. Suppl. 490, 1–84 (1979).

    CAS  PubMed  Google Scholar 

  92. Biancone, L. et al. Local injection of Infliximab in the postoperative recurrence of Crohn's disease. Gastrointest. Endosc. 63, 486–492 (2006).

    Article  PubMed  Google Scholar 

  93. Yamamoto, T., Umegae, S. & Matsumoto, K. Impact of infliximab therapy after early endoscopic recurrence following ileocolonic resection of Crohn's disease: a prospective pilot study. Inflamm. Bowel Dis. 15, 1460–1466 (2009).

    Article  PubMed  Google Scholar 

  94. Boueyre, E. et al. Efficacy of anti-TNF on severe postoperative endoscopic recurrence in Crohn's disease. Gastroenterology 142, S-660 (2012).

    Google Scholar 

  95. Regueiro, M. et al. 4.5 Yr follow-up of patients enrolled in the randomized controlled trial (RCT) of infliximab (Inf) for prevention of postoperative Crohn's disease (CD). Gastroenterology 138, S694 (2010).

    Article  CAS  Google Scholar 

  96. Gisbert, J. P. & Panés, J. Loss of response and requirement of infliximab dose intensification in Crohn's disease: a review. Am. J. Gastroenterol. 104, 760–767 (2009).

    Article  CAS  PubMed  Google Scholar 

  97. Danese, S. Mechanisms of action of infliximab in inflammatory bowel disease: an anti-inflammatory multitasker. Dig. Liver Dis. 40, S225–S228 (2008).

    Article  CAS  PubMed  Google Scholar 

  98. Barnes, M. J. & Powrie, F. Regulatory T cells reinforce intestinal homeostasis. Immunity 31, 401–411 (2009).

    Article  CAS  PubMed  Google Scholar 

  99. Miossec, P., Korn, T. & Kuchroo, V. K. Interleukin-17 and type 17 helper T cells. N. Engl. J. Med. 361, 888–898 (2009).

    Article  CAS  PubMed  Google Scholar 

  100. Bernstein, C. N. Anti-tumor necrosis factor therapy in Crohn's disease: more information and more questions about the long term. Clin. Gastroenterol. Hepatol. 8, 556–558 (2010).

    Article  PubMed  Google Scholar 

  101. 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 (2012).

    Article  CAS  PubMed  Google Scholar 

  102. Waugh, A. W. et al. Maintenance of clinical benefit in Crohn's disease patients after discontinuation of infliximab: long-term follow-up of a single centre cohort. Aliment. Pharmacol. Ther. 32, 1129–1134 (2010).

    Article  CAS  PubMed  Google Scholar 

  103. Schnitzler, F. et al. Long-term outcome of treatment with infliximab in 614 patients with Crohn's disease: results from a single-centre cohort. Gut 58, 492–500 (2009).

    Article  CAS  PubMed  Google Scholar 

  104. Baert, F. et al. Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn's disease. Gastroenterology 138, 463–468 (2010).

    Article  PubMed  Google Scholar 

  105. Steenholdt, C. et al. Outcome after discontinuation of infliximab in patients with inflammatory bowel disease in clinical remission: an observational Danish single center study. Scand. J. Gastroenterol. 47, 518–527 (2012).

    Article  CAS  PubMed  Google Scholar 

  106. Sorrentino, D. et al. Low dose infliximab for prevention of postoperative recurrence of Crohn's disease: long term follow-up and impact of infliximab trough levels and antibodies to infliximab. Gastroenterology (in press).

  107. Van de Casteele, N. et al. Results on the optimisation phase of the prospective controlled trough level adapted infliximab treatment (TAXIT) trial. Gastroenterology 142, S1159 (2012).

    Google Scholar 

  108. Steenholdt, C. et al. Cut-off levels and diagnostic accuracy of infliximab trough levels and anti-infliximab antibodies in Crohn's disease. Scand. J. Gastroenterol. 46, 310–318 (2011).

    Article  CAS  PubMed  Google Scholar 

  109. Cassinotti, A. & Travis, S. Incidence and clinical significance of immunogenicity to infliximab in Crohn's disease: a critical systematic review. Inflamm. Bowel Dis. 15, 1264–1275 (2009).

    Article  PubMed  Google Scholar 

  110. Bongartz, T. et al. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies. JAMA 295, 2275–2278 (2006).

    Article  CAS  PubMed  Google Scholar 

  111. Buisson, A., Chevaux, J. B., Bommelaer, G. & Peyrin-Biroulet, L. Diagnosis, prevention and treatment of postoperative Crohn's disease recurrence. Dig. Liver Dis. 44, 453–460 (2012).

    Article  PubMed  Google Scholar 

  112. Schwartz, M. & Regueiro, M. Prevention and treatment of postoperative Crohn's disease recurrence: an update for a new decade. Curr. Gastroenterol. Rep. 13, 95–100 (2011).

    Article  PubMed  Google Scholar 

  113. Spinelli, A., Sacchi, M., Fiorino, G., Danese, S. & Montorsi, M. Risk of postoperative recurrence and postoperative management of Crohn's disease. World J. Gastroenterol. 17, 3213–3219 (2011).

    PubMed  PubMed Central  Google Scholar 

  114. Van Assche, G. et al. European Crohn's and Colitis Organisation (ECCO). The second European evidence-based Consensus on the diagnosis and management of Crohn's disease: Special situations. J. Crohns Colitis 4, 63–101 (2010).

    Article  PubMed  Google Scholar 

  115. Peyrin-Biroulet, L., Oussalah, A., Roblin, X. & Sparrow, M. P. The use of azathioprine in Crohn's disease during pregnancy and in the post-operative setting: a worldwide survey of experts. Aliment. Pharmacol. Ther. 33, 707–713 (2011).

    Article  CAS  PubMed  Google Scholar 

  116. Yamamoto, T. Prevention of recurrence after surgery for Crohn's disease: efficacy of infliximab. World J. Gastroenterol. 16, 5405–5410 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  117. Borowiec, A. M. & Fedorak, R. N. Predicting, treating and preventing postoperative recurrence of Crohn's disease: the state of the field. Can. J. Gastroenterol. 25, 140–146 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  118. De Cruz, P. et al. Clinical risk stratification predicts development of endoscopic recurrence after Crohn's disease surgery: early results from the POCER Study. Gastroenterology 142, S568 (2012).

    Article  Google Scholar 

  119. Kandiel, A. et al. Increased risk of lymphoma among inflammatory bowel disease patients treated with azathioprine and 6-mercaptopurine. Gut 54, 1121–1125 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Reinisch, W. et al. Azathioprine versus mesalazine for prevention of postoperative clinical recurrence in patients with Crohn's disease with endoscopic recurrence: efficacy and safety results of a randomised, double-blind, double-dummy, multicentre trial. Gut 59, 752–759 (2010).

    Article  CAS  PubMed  Google Scholar 

  121. Yamamoto, T., Fazio, V. W. & Tekkis, P. P. Safety and efficacy of strictureplasty for Crohn's disease: a systematic review and meta-analysis. Dis. Colon Rectum 50, 1968–1986 (2007).

    Article  PubMed  Google Scholar 

  122. US National Library of Medicine. ClinicalTrials.gov [online], (2013).

  123. Danese, S., Fiorino, G. & Reinisch, W. Review article: Causative factors and the clinical management of patients with Crohn's disease who lose response to anti-TNF-α therapy. Aliment. Pharmacol. Ther. 34, 1–10 (2011).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Gastroenterology, Virginia Tech-Carilion School of Medicine, 3 Riverside Circle, Roanoke, 24016, VA, USA

    Dario Sorrentino

  2. Department of Clinical and Experimental Medical Sciences, University of Udine School of Medicine, Via Colugna 50, Udine, 33100, Italy

    Dario Sorrentino

Authors
  1. Dario Sorrentino
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

D. Sorrentino has received consulting fees and served on advisory committees or review panels for Abbott Laboratories, AstraZeneca, Centocor, Ferring Pharmaceuticals, Giuliani SpA, Hoffmann LaRoche, Janssen, MSD, Schering–Plough Corporation.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sorrentino, D. State-of-the-art medical prevention of postoperative recurrence of Crohn's disease. Nat Rev Gastroenterol Hepatol 10, 413–422 (2013). https://doi.org/10.1038/nrgastro.2013.69

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrgastro.2013.69

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing