Review Article

Prevention of Postoperative Recurrence in CD: Tailoring Treatment to Patient Profile

Author(s): Marjorie Argollo, Paulo Gustavo Kotze, Laura Lamonaca, Daniela Gilardi, Federica Furfaro, Takayuki Yamamoto and Silvio Danese*

Volume 20, Issue 13, 2019

Page: [1327 - 1338] Pages: 12

DOI: 10.2174/1389450120666190320110809

Price: $65


Crohn’s disease (CD) is an immune-mediated condition characterized by the transmural inflammation of the gut tissue, associated with progressive bowel damage often leading to surgical intervention. As operative resection of the damaged segment is not curative, a majority of patients undergoing intestinal resections for complicated CD present disease recurrence within 3 years after the intervention. Postoperative recurrence can be defined as endoscopic, clinical, radiological or surgical. Endoscopic recurrence rates within 1 year exceed 60% and the severity, according to the Rutgeerts’ score, is associated with worse prognosis and can predict clinical recurrence (in up to 1/3 of the patients). Most importantly, about 50% of patients will undergo a reoperation after 10 years of their first intestinal resection. Therefore, the prevention of postoperative recurrence in CD remains a challenge in clinical practice and should be properly managed. We aim to summarize the most recent data on the definition, risk factors, assessment and treatment of postoperative CD recurrence.

Keywords: Crohn's disease, postoperative recurrence, prevention, surgery treatment, immune-mediated, transmural inflammation.

Graphical Abstract
Peyrin-Biroulet L, Bouhnik Y, Roblin X, et al. French national consensus clinical guidelines for the management of Crohn’s disease. Dig Liver Dis 2017; 49(4): 368-77.Available from:.
[ j.dld.2016.12.008]
Fiorino G, Bonifacio C, Allocca M, et al. Bowel damage as assessed by the lémann index is reversible on anti-tnf therapy for crohn’s disease. J Crohn’s Colitis 2015; 9(8): 633-9.
Pariente B, Mary JY, Danese S, et al. Development of the Lémann index to assess digestive tract damage in patients with Crohn’s disease. Gastroenterology 2015; 148(1): 52-63.e3.Available from:.
Fortinsky KJ, Kevans D, Qiang J, et al. Rates and predictors of endoscopic and clinical recurrence after primary ileocolic resection for crohn’s disease. Dig Dis Sci 2017; 62(1): 188-96.
Buisson A, Chevaux JB, Bommelaer G, Peyrin-Biroulet L. Diagnosis, prevention and treatment of postoperative Crohn’s disease recurrence. Dig Liver Dis 2012; 44(6): 453-60.Available from:.
Kotze PG, Yamamoto T, Damiao AOMC. Postoperative approach for crohn’s disease: The right therapy to the right patient. Curr Drug Targets 2018; 19(7): 729-39.
Nguyen V, Kanth R, Gazo J, Sorrentino D. Management of post-operative Crohn’s disease in 2017: where do we go from here? Expert Rev Gastroenterol Hepatol 2016; 10(11): 1257-69.Available from:.
Yang KM, Yu CS, Lee JL, et al. Risk factors for postoperative recurrence after primary bowel resection in patients with Crohn’s disease. World J Gastroenterol 2017; 23(38): 7016-24.
Peyrin-Biroulet L, Loftus EV, Colombel JF, Sandborn WJ. The natural history of adult crohn’s disease in population-based cohorts. Gastroenterology 2010; 105(2): 289-97.
Buisson A, Chevaux JB, Allen PB, Bommelaer G, Peyrin-Biroulet L. Review article: the natural history of postoperative Crohn’s disease recurrence. Aliment Pharmacol Ther 2012; 36(6): 625-33.
Rutgeerts P, Geboes K, Vantrappen G, et al. Predictability of the postoperative course of Crohn’s disease. Gastroenterology 1990; 99(4): 956-63.
Rutgeerts P, Geboes K, Vantrappen G, et al. Natural history of recurrent Crohns disease at the ileocolonic anastomosis after curative surgery. Gut 1984; 25(6): 665-72.
Olaison G, Smedh K, Sjödahl R. Natural course of Crohn’s disease after ileocolic resection: endoscopically visualised ileal ulcers preceding symptoms. Gut 1992; 33(3): 331-5.
Bernell O, Lapidus A, Hellers G. Risk factors for surgery and recurrence in 907 patients with primary ileocaecal Crohn’s disease. Br J Surg 2000; 87(12): 1697-701.
Gionchetti P, Dignass A, Danese S, et al. 3rd European evidencebased consensus on the diagnosis and management of crohn’s disease 2016: part 2: surgical management and special situations on behalf of ECCO. J Crohn’s Colitis 2017; 135-49.
[ jjw 169]
Wright EK, Kamm MA, Wagner J, et al. Microbial factors associated with postoperative crohn’s disease recurrence. J Crohn’s Colitis 2017; 11(2): 191-203.
Nunes T, Etchevers MJ, García-Sánchez V, et al. Impact of smoking cessation on the clinical course of Crohn’s disease under current therapeutic algorithms: A multicenter prospective study. Am J Gastroenterol 2016; 111(3): 411-9.
Reese GE, Nanidis T, Borysiewicz C, et al. The effect of smoking after surgery for Crohn’s disease: a meta-analysis of observational studies. Int J Color Dis 2008; 23(12): 1213-21.
Lautenbach E, Berlin JA, Lichtenstein GR. Risk factors for early postoperative recurrence of Crohn’s disease. Gastroenterology 1998; 115(2): 259-67.
Simillis C, Yamamoto T, Reese GE, et al. A meta-analysis comparing incidence of recurrence and indication for reoperation after surgery for perforating versus nonperforating Crohn’s disease. Am J Gastroenterol 2008; 103(1): 196-205.
Bressenot A, Peyrin-Biroulet L. Histologic features predicting postoperative Crohn’s disease recurrence. Inflamm Bowel Dis 2015; 21(2): 468-75.
Collins M, Sarter H, Gower-Rousseau C, et al. Previous exposure to multiple anti-tnf is associated with decreased efficiency in preventing postoperative crohn’s disease recurrence. J Crohn’s Colitis 2017; 21(2): 468-75.
Holt DQ, Moore GT, Strauss BJG, Hamilton AL, De Cruz P, Kamm MA. Visceral adiposity predicts post-operative Crohn’s disease recurrence. Aliment Pharmacol Ther 2017; 45(9): 1255-64.
Nguyen VQ, Mays JL, Lang M, et al. Knowledge gaps in the management of postoperative crohn’s disease: A US National Survey. Dig Dis Sci 2018; 63(1): 53-60.
Pascua M, Su C, Lewis JD, Brensinger C, Lichtenstein GR. Meta-analysis: factors predicting post-operative recurrence with placebo therapy in patients with Crohn’s disease. Aliment Pharmacol Ther 2008; 28(5): 545-56.
Rispo A, Imperatore N, Testa A, et al. Diagnostic accuracy of ultrasonography in the detection of postsurgical recurrence in crohn’s disease: a systematic review with meta-analysis. Inflamm Bowel Dis 2018; 24(5): 977-88.
Rimola J, Rodriguez S, García-Bosch O, et al. Magnetic resonance for assessment of disease activity and severity in ileocolonic Crohn’s disease. Gut 2009; 58(8): 1113-20.
Rimola J, Ordás I, Rodriguez S, et al. Magnetic resonance imaging for evaluation of Crohn’s disease: Validation of parameters of severity and quantitative index of activity. Inflamm Bowel Dis 2011; 17(8): 1759-68.
Ordás I, Rimola J, Rodríguez S, et al. Accuracy of magnetic resonance enterography in assessing response to therapy and mucosal healing in patients with Crohn’s disease. Gastroenterology 2014; 146(2): 374-82.e1.
Baillet P, Cadiot G, Goutte M, et al. Faecal calprotectin and magnetic resonance imaging in detecting Crohn’s disease endoscopic postoperative recurrence. World J Gastroenterol 2018; 24(5): 641-50.
Koilakou S, Sailer J, Peloschek P, et al. Endoscopy and MR enteroclysis: Equivalent tools in predicting clinical recurrence in patients with Crohn’s disease after ileocolic resection. Inflamm Bowel Dis 2010; 16(2): 198-203.
Wright EK, Kamm MA, De Cruz P, et al. Measurement of fecal calprotectin improves monitoring and detection of recurrence of Crohn’s disease after surgery. Gastroenterology 2015; 148(5): 938-947.e1.
[ j.gastro.2015.01.026]
Boschetti G, Laidet M, Moussata D, et al. Levels of fecal calprotectin are associated with the severity of postoperative endoscopic recurrence in asymptomatic patients with Crohn’s disease. Am J Gastroenterol 2015; 110(6): 865-72.
Garcia-Planella E, Mañosa M, Cabré E, et al. Fecal calprotectin levels are closely correlated with the absence of relevant mucosal lesions in postoperative Crohn’s Disease. Inflamm Bowel Dis 2016; 22(12): 2879-85.
De Cruz P, Kamm MA, Hamilton AL, et al. Efficacy of thiopurines and adalimumab in preventing Crohn’s disease recurrence in high-risk patients - A POCER study analysis. Aliment Pharmacol Ther 2015; 42(7): 867-79.
Gecse K, Lowenberg M, Bossuyt P, et al. Agreement among experts in the endoscopic evaluation of postoperative recurrence in crohn’s disease using the rutgeerts score. Gastroenterology 2014; 146(5)S1(S-227).
Riviere P, Vermeire S, Irles-Depe M, et al. No change in determining crohn’s disease recurrence or need for endoscopic or surgical intervention with modification of rutgeerts’ scoring system. Clin Gastroenterol Hepatol 2019; 17(8): 1643-5.
Marteau P, Laharie D, Colombel JF, et al. Interobserver variation study of the rutgeerts score to assess endoscopic recurrence after surgery for Crohn’s disease. J Crohn’s Colitis 2016; 10(9): 1001-5. Epub 2016 Apr 11.
Regueiro M, Feagan BG, Zou B, et al. Infliximab reduces endoscopic, but not clinical, recurrence of crohn’s disease after ileocolonic resection. Gastroenterology 2016; 150(7): 1568-78.
Mowat C, Arnott I, Cahill A, et al. Mercaptopurine versus placebo to prevent recurrence of Crohn’s disease after surgical resection (TOPPIC): a multicentre, double-blind, randomised controlled trial. Lancet Gastroenterol Hepatol 2016; 1(4): 273-82.
D’Haens GR, Vermeire S, Van Assche G, et al. Therapy of metronidazole with azathioprine to prevent postoperative recurrence of crohn’s disease: A controlled randomized trial. Gastroenterology 2008; 135(4): 1123-9.
Managing Crohn’s disease after surgery: A Patient Guide. Gastroenterology 2017; 152(1): 296-7.
Domènech E, Garcia V, Iborra M, et al. Incidence and management of recurrence in patients with crohn’s disease who have undergone intestinal resection: the practicrohn study. Inflamm Bowel Dis 2017; 23(10): 1840-6.
Candia R, Naimark D, Sander B, Nguyen GC. Cost-utility analysis: thiopurines plus endoscopy-guided biological step-up therapy is the optimal management of postoperative Crohn’s Disease. Inflamm Bowel Dis 2017; 23(11): 1930-40.
Orel R, Trop TK. Intestinal microbiota, probiotics and prebiotics in inflammatory bowel disease. World J Gastroenterol 2014; 20(33): 11505-24.
Prantera C, Scribano ML, 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 2002; 51(3): 405-9.
Marteau P, Lémann M, Seksik 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 2006; 55(6): 842-7.
Van Gossum A, Dewit O, Louis E, 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 2007; 13(2): 135-42.
Doherty GA, Bennett GC, Cheifetz AS, Moss AC. Meta-analysis: targeting the intestinal microbiota in prophylaxis for post-operative Crohn’s disease. Aliment Pharmacol Ther 2010; 31(8): 802-9.
De Cruz P, Kamm MA, Hamilton AL, et al. Crohn’s disease management after intestinal resection: A randomised trial. Lancet 2015; 385(9976): 1406-7.Available from:.
Rutgeerts P, Hiele M, Geboes K, et al. Controlled trial of metronidazole treatment for prevention of crohn’s recurrence after ileal resection. Gastroenterology 1995; 108(6): 1617-21.
Rutgeerts P, Van Assche G, Vermeire S, et al. Ornidazole for prophylaxis of postoperative Crohn’s disease recurrence: A randomized, double-blind, placebo-controlled trial. Gastroenterology 2005; 128(4): 856-61.
Moja L, Danese S, Fiorino G, Del Giovane C, Bonovas S. Systematic review with network meta-analysis: comparative efficacy and safety of budesonide and mesalazine (mesalamine) for Crohn’s disease. Aliment Pharmacol Ther 2015; 41(11): 1055-65.Epub 2015 Apr 13.
Hellers G, Cortot A, Jewell D, et al. Oral budesonide for prevention of postsurgical recurrence in Crohn’s disease. The IOIBD budesonide study group. Gastroenterology 1999; 116(2): 294-300.
Ewe K, Bottger T, Buhr HJ, Ecker KW, Otto HF. 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 1999; 11(3): 277-82.
Punchard NA, Greenfield SM, Thompson RP. Mechanism of action of 5-arninosalicylic acid. Mediators Inflamm. 1992; 1(3): 151-65.Available from: . articlerender. fcgi?artid=2365334&tool=pmcentrez&rendertype= abstract
Ong MS, Grand RJ, Mandl KD. Trends in Pharmacologic Interventions for Preventing Recurrence of Crohn’s Disease after Ileocolonic Surgery. Inflamm Bowel Dis 2016; 22(10): 2432-41.
Allocca M, Landi R, Bonovas S, et al. Effectiveness of mesalazine, thiopurines and tumour necrosis factor antagonists in preventing post-operative crohn’s disease recurrence in a real-life setting. Digestion 2017; 96(3): 166-72.
Yang Z, Ye X, Wu Q, Wu K, Fan D. A network meta-analysis on the efficacy of 5-aminosalicylates , immunomodulators and biologics for the prevention of postoperative recurrence in Crohn ’ s disease [Internet]. Int J Surgery 2014; 12:: 516-22.Available from:.
Peyrin-Biroulet L, Deltenre P, Ardizzone S, et al. Azathioprine and 6-mercaptopurine for the prevention of postoperative recurrence in Crohn’s disease: A meta-analysis. Am J Gastroenterol 2009; 104(8): 2089-96.
Gordon M, Taylor K, Akobeng AK, Thomas AG. Azathioprine and 6-mercaptopurine for maintenance of surgically-induced remission in Crohn’s disease. Cochrane Database Syst Rev 2014; (8): CD010233.
Hanauer SB, Korelitz BI, Rutgeerts P, et al. Postoperative maintenance of Crohn’s disease remission with 6-mercaptopurine, mesalamine, or placebo: A 2-year trial. Gastroenterology 2004; 127(3): 723-9.
Argollo M, Fiorino G, Hindryckx P, Peyrin-Biroulet L, Danese S. Novel therapeutic targets for inflammatory bowel disease. J Autoimmun 2017; 85: 103-16.
Sorrentino Dario, Terrosu Giovanni, Avellini Claudio, et al. Infliximab with low-dose methotrexate for prevention of postsurgical recurrence of ileocolonic crohn disease. Arch Intern Med 2007; 167(16): 1804-7.
Regueiro M, Schraut W, Baidoo L, et al. Infliximab prevents Crohn’s disease recurrence after ileal resection. Gastroenterology 2009; 136(2): 441-50.e1.
Wilcox CM. Low-dose maintenance therapy with infliximab prevents postsurgical recurrence of crohn’s disease. Clin Gastroenterol Hepatol [Internet] 2010; 8(7): e78-9.Available from:.
Regueiro M, Kip KE, Baidoo L, Swoger JM, Schraut W. Postoperative therapy with infliximab prevents long-term crohn’s disease recurrence. Clin Gastroenterol Hepatol [Internet] 2014; 12(9)1494-1502.e1 Available from:.
Aguas M, Bastida G, Cerrillo E, et al. Adalimumab in prevention of postoperative recurrence of Crohn’s disease in high-risk patients. World J Gastroenterol 2012; 18(32): 4391-8.
Papamichael K, Archavlis E, Lariou C, Mantzaris GJ. Adalimumab for the prevention and/or treatment of post-operative recurrence of Crohn’s disease: A prospective, two-year, single center, pilot study. J Crohn’s Colitis [Internet] 2012; 6(9): 924-31. Available from:.
López-Sanromán A, Vera-Mendoza I, Domènech E, et al. Adalimumab vs azathioprine in the prevention of postoperative crohn’s disease recurrence. A GETECCU Randomised Trial. J Crohn’s Colitis [Internet] 2017; 1293-301.Available from:. https://academic.
Sakuraba A, Sato T, Matsukawa H, 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 2012; 27(7): 947-52.
Yoshida K, Fukunaga K, Ikeuchi H, 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 2012; 18(9): 1617-23.
Savarino E, Bodini G, Dulbecco P, et al. Adalimumab is more effective than azathioprine and mesalamine at preventing postoperative recurrence of Crohn’s disease: A randomized controlled trial. Am J Gastroenterol [Internet] 2013; 108(11): 1731-42. Available from:.
[ ajg.2013.287]
Armuzzi A, Felice C, Papa A, et al. Prevention of postoperative recurrence with azathioprine or infliximab in patients with Crohn’s disease: An open-label pilot study. J Crohn’s Colitis [Internet] 2013; 7(12): e623-9. Available from:.
Tursi A, Elisei W, Picchio M, et al. Comparison of the effectiveness of infliximab and adalimumab in preventing postoperative recurrence in patients with Crohn’s disease: an open-label, pilot study. Tech Coloproctol 2014; 18(11): 1041-6.
Kotze PG, Yamamoto T, Danese S, et al. Direct retrospective comparison of adalimumab and infliximab in preventing early postoperative endoscopic recurrence after ileocaecal resection for Crohn’s disease: Results from the MULTIPER database. J Crohn’s Colitis 2015; 9(7): 541-7.
Argollo M, Fiorino G, Peyrin-Biroulet L, Danese S. Vedolizumab for the treatment of Crohn’s disease. Expert Rev Clin Immunol 2018; 14(3): 179-89.
Baumgart DC, Bokemeyer B, Drabik A, Stallmach A, Schreiber S. Vedolizumab induction therapy for inflammatory bowel disease in clinical practice--a nationwide consecutive German cohort study. Aliment Pharmacol Ther 2016; 43(10): 1090-102.
Hanauer S, Colombel J, Sands BE, et al. Vedolizumab as Induction and Maintenance Therapy for Crohn’s Disease. N Engl J Med 2013; 369(8): 711-21.
Sandborn WJ, Feagan BG, Rutgeerts P, et al. Vedolizumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med [Internet] 2013; 369(8): 711-21. Available from:. pubmed/23964932%5Cn//
Sands BE, Sandborn WJ, Van Assche G, et al. Vedolizumab as induction and maintenance therapy for crohn’s disease in patients naive to or who have failed tumor necrosis factor antagonist therapy. Inflamm Bowel Dis 2017; 23(1): 97-106.
Noman M, Ferrante M, Bisschops R, et al. Vedolizumab induces long term mucosal healing in patients with Crohn’s disease and ulcerative colitis. J Crohn’s Colitis 2017; 11(9): 1085-9.
Vermeire S, Loftus EVJ, Colombel J-F, et al. Long-term efficacy of vedolizumab for crohn’s disease. J Crohn’s Colitis 2017; 11(4): 412-24.
Yamada A, Komaki Y, Patel N, et al. The use of vedolizumab in preventing postoperative recurrence of crohn’s disease. Inflamm Bowel Dis [Internet] 2018; 24(3): 502-9.Available from:. article/24/3/502/4863704
Scherl EJ, Kumar S, Warren RU. Review of the safety and efficacy of ustekinumab. Therap Adv Gastroenterol [Internet] 2010; 3(5): 321-8.Available from: .
Sandborn WJ, Gasink C, Gao LL, et al. Ustekinumab induction and maintenance therapy in refractory Crohn’s disease. N Engl J Med [Internet] 2012; 367(16): 1519-28.Available from:.
Feagan BG, Sandborn WJ, Gasink C, et al. Ustekinumab as induction and maintenance therapy for crohn’s disease. N Engl J Med [Internet] 2016; 375(20): 1946-60. Available from:. 10.1056/NEJMoa1602773
Scherl EJ, Kumar S, Warren RU. Review of the safety and efficacy of ustekinumab. Therapeutic Advances in Gastroenterology 2010; 3(5): 321-8.
Kotze PG, Ma C, Almutairdi A, Panaccione R. Clinical utility of ustekinumab in Crohn’s disease. J Inflamm Res 2018; 11: 35-47.
Fazio VW, Marchetti F, Church M, et al. Effect of resection margins on the recurrence of Crohn’s disease in the small bowel. A randomized controlled trial. Ann Surg 1996; 224(4): 563-71.
McLeod RS, Wolff BG, Ross S, Parkes R, McKenzie M. Recurrence of Crohn’s disease after ileocolic resection is not affected by anastomotic type: results of a multicenter, randomized, controlled trial. Dis Colon Rectum 2009; 52(5): 919-27.
Stocchi L, Milsom JW, Fazio VW. Long-term outcomes of laparoscopic versus open ileocolic resection for Crohn’s disease: Follow-up of a prospective randomized trial. Surgery 2008; 144(4): 622-8.
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 2007; 25(1): 67-72.
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 2013; 28(3): 335-40.
Esaki M, Matsumoto T, Hizawa K, 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 2005; 40(12): 1431-7.
Doherty G, Katsanos KH, Burisch J, et al. European Crohn’s and colitis organisation topical review on treatment withdrawal [‘exit strategies’] in inflammatory bowel disease. J Crohn’s Colitis 2018; 12(1): 17-31.
Domènech E, Hinojosa J, Nos P, et al. Clinical evolution of luminal and perianal Crohn’s disease after inducing remission with infliximab: How long should patients be treated? Aliment Pharmacol Ther 2005; 22(11-12): 1107-13.
Waugh AWG, Garg S, Matic K, 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 2010; 32(9): 1129-34.
Papamichael K, Vande Casteele N, Gils A, et al. Long-term outcome of patients with crohn’s disease who discontinued infliximab therapy upon clinical remission. Clin Gastroenterol Hepatol [Internet] 2015; 13(6): 1103-10.Available from: .
Louis E, Mary JY, Verniermassouille G, et al. Maintenance of remission among patients with Crohn’s disease on antimetabolite therapy after infliximab therapy is stopped. Gastroenterology [Internet] 2012; 142(1): 63-70.e5.Available from: .

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