De-escalation of Therapy in Inflammatory Bowel Disease
Purpose of Review
Currently, inflammatory bowel disease treatment is based on immunomodulators (IM) and/or biologic as this strategy may prevent the development of irreversible damage. Nevertheless, long-term treatment may be associated with non-negligible side effects and with high costs, and therefore the question on whether therapy can be de-escalated is often posed in clinical practice.
Recent studies have shown a predictable rate of relapse after stop biologic or IM therapy withdrawal. Overall, around 40–50% of patients will eventually relapse over the following year after drug withdrawal, and the rates will increase over time. Stratification of patients and therapeutic drug monitoring could be promising alternatives to guide therapeutic management.
We reviewed the current evidence on de-escalation strategy and summarised the recent results on discontinuation and dose reduction. Nowadays, de-escalation strategy is still a case-by-case decision in highly selected patients.
KeywordsImmunomodulators Anti-TNF Withdrawal Relapse Dose reduction Therapeutic drug monitoring
All authors contributed to the manuscript concept and design. CG reviewed the literature and drafted the manuscript. All authors critically revised the manuscript. All authors have approved the manuscript.
Compliance With Ethical Standards
Conflict of Interest
Joana Torres reports consulting fees from Takeda and AbbVie.
Jean-Frederic Colombel reports grants from Janssen and Janssen and Takeda; is working as a consultant and/or speaker for AbbVie, Amgen, Boehringer-Ingelheim, Ferring Pharmaceuticals, Genentech, Janssen and Janseen, Medimmune, Merck & Co., Nextbiotix, Novartis Pharmaceuticals Corporation, Otsuka Pharmaceutical Development and Commercialization, Inc., Pfizer, Protagonist, Second Genome, Gilead, Seres Therapeutics, Shire, Takeda, and Theradiag; and holds stock options with Intestinal Biotech Development and Genfit.
Catarina Frias Gomes declares no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance
- 1.Torres J, Mehandru S, Colombel JF, Peyrin-Biroulet L. Crohn’s disease. Lancet. 2016;16:31711.Google Scholar
- 6.Siegel, Corey A. et al. International differences in gastroenterologists' perspective on stopping therapy for patients with Crohn's disease. Gastroenterology. 2017;152(5)S371.Google Scholar
- 7.Siegel C, Thompson K, Walls D, Gollins J, Buisson A, Olympie A, et al. DOP032 Crohn’s disease patients’ perspectives towards de-escalating immunosuppressive therapy: a comparative French and American survey. J Crohns Colitis. 2018;12(Suppl 1):S053.Google Scholar
- 10.Guidance on the use of infliximab and adalimumab for the treatment of Crohn's disease. NICE technology appraisal guidance 187 (2010).Google Scholar
- 12.Magro F, Gionchetti P, Eliakim R, Ardizzone S, Armuzzi A, Barreiro-de Acosta M, et al. Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 1: definitions, diagnosis, extra-intestinal manifestations, pregnancy, cancer surveillance, surgery, and ileo-anal pouch disorders. J Crohn’s Colitis. 2017;11(6):649–70.CrossRefGoogle Scholar
- 18.Boyapati RK, Torres J, Palmela C, Parker, CE, Silverberg OM, Upadhyaya SD et al. Withdrawal of immunosuppressant or biologic therapy for patients with quiescent Crohn's disease. Cochrane Database Syst Rev. 2018;12(5):CD012540.Google Scholar
- 23.• Torres J, Boyapati R, Kennedy N, Louis E, Colombel J, Satsangi J. Systematic review of effects of withdrawal of Immunomodulators or biologic agents from patients with inflammatory bowel disease. Gastroenterology. 2015;149(7):1716–30. This article provides the relapse rates after imunomodulator, combination therapy and biologic withdrawal. Factors associated with relapse and response to re-treatment were also highlighted. CrossRefPubMedGoogle Scholar
- 26.Filippi J, Laharie D, Michiels C, Flamand M, Bouguen G, Nancey S, et al. Efficacy of sustained combination therapy for at least 6 months with thiopurines and infliximab in patients with ulcerative colitis in clinical remission: a retrospective multicenter French experience. J Crohn’s Colitis. 2015;9(3):252–8.CrossRefGoogle Scholar
- 30.• Casanova MJ, Chaparro M, García-Sánchez V, Nantes O, Leo E, Rojas-Feria M, et al. Evolution after anti-TNF discontinuation in patients with inflammatory bowel disease: a multicenter long-term follow-up study. Am J Gastroenterol. 2017;112(1):120–31. Casanova et al. found that the incidence rate relapse was 19 and 17% per patient-year in Crohn’s disease and ulcerative colitis, after anti-TNF withdrawal. CrossRefPubMedGoogle Scholar
- 31.Kennedy NA, Warner B, Johnston EL, Flanders L, Hendy P, Ding NS, et al. Relapse after withdrawal from anti-TNF therapy for inflammatory bowel disease: an observational study, plus systematic review and meta-analysis. Aliment Pharmacol Ther. 2016;43(8):910–23.CrossRefPubMedPubMedCentralGoogle Scholar
- 32.Fiorino G, Cortes PN, Ellul P, Felice C, Karatzas P, Silva M, et al. Discontinuation of infliximab in patients with ulcerative colitis is associated with increased risk of relapse: a multinational retrospective cohort study. Clin Gastroenterol Hepatol. 2016;14(10):1426–32.CrossRefPubMedGoogle Scholar
- 33.Louis E, Mary J, Vernier-massouille G, Grimaud J, Bouhnik Y, Laharie D, et al. Maintenance of remission among patients with Crohn’s disease on antimetabolite therapy after infliximab therapy is stopped. Gastroenterol Hepatol (N Y). 2012;142:63–70.Google Scholar
- 34.Brooks AJ, Sebastian S, Cross SS, Robinson K, Warren L, Wright A, et al. Outcome of elective withdrawal of anti-tumour necrosis factor-α therapy in patients with Crohn’s disease in established remission. J Crohn’s Colitis. 2017;11(12):1456–1462.Google Scholar
- 35.Dai C, Liu WX, Jiang M, Sun MJ. Mucosal healing did not predict sustained clinical remission in patients with IBD after discontinuation of one-year infliximab therapy. PLoS One. 2014;9(10):1–6.Google Scholar
- 36.Kennedy NA, Warner BJE, et al. DOP035. Anti-TNF withdrawal in IBD: relapse and recapture rates and predictive factors from 160 patients in a pan-UK study. J Crohns Colitis. 9(Suppl 1):S41–2.Google Scholar
- 37.• Reenaers C, Mary J, Nachury M, Bouhnik Y, Laharie D, Allez M, et al. Outcomes 7 years after infliximab withdrawal for patients with Crohn’s disease in sustained remission. Clin Gastroenterol Hepatol. 2017;S1542–3565(17):31225–9. Reenaers et al. reported the long-term outcomes from the STORI trial. Google Scholar
- 40.Bortlik M, Duricova D, Machkova N, Hruba V, Lukas M, Mitrova K. Discontinuation of anti-tumor necrosis factor therapy in inflammatory bowel disease patients: a prospective observation. Scand J Gastroenterol. 2015:1–7.Google Scholar
- 45.Molander P, Färkkilä M, Salminen K, Kemppainen H, Blomster T, Koskela R, et al. Outcome after discontinuation of TNFα-blocking therapy in patients with inflammatory bowel disease in deep remission. J Crohns Colitis. 2014;20(6):1.Google Scholar
- 51.Kennedy NA, Kalla R, Warner B, Gambles CJ, Musy R, Reynolds S, 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. 2014;40(11–12):1313–23.CrossRefPubMedPubMedCentralGoogle Scholar