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Cessation of Biologics: Can It Be Done?

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Treatment of Inflammatory Bowel Disease with Biologics

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Abstract

Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory conditions of the gastrointestinal tract characterized by a relapsing and remitting course which may lead to progressive bowel damage. Historically, inflammatory bowel disease (IBD) has been managed with corticosteroids, 5-ASA agents, and immunomodulators (thiopurines or methotrexate). Up to 80% of individuals with CD and 30% with UC require surgical management to remove diseased bowel. Biologic therapies, in particular, anti-TNF-α agents, have significantly improved the management of IBD and have been associated with mucosal healing. Mucosal healing is associated with lower rates of hospitalization, surgery, postoperative recurrence, colorectal cancer, and improved quality of life. However, individuals can lose response to anti-TNF-α therapies over time either due to immunogenicity or mechanistic escape. Furthermore, TNF antagonists are associated with side effects that are concerning to both physicians and patients including an increased risk of infection, and possibly lymphoma and solid organ malignancy. They are also associated with considerable cost. Therefore, one of the most vexing questions is, can anti-TNF-α therapy be stopped? In this book chapter, we will focus on the why, when, who might consider cessation of anti-TNF-α therapy, and how this may be best performed.

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References

  1. Baumgart DC, Sandborn WJ. Crohn’s disease. Lancet. 2012;380(9853):1590–605.

    Article  PubMed  Google Scholar 

  2. Ordas I, Eckmann L, Talamini M, Baumgart DC, Sandborn WJ. Ulcerative colitis. Lancet. 2012;380(9853):1606–19.

    Article  PubMed  Google Scholar 

  3. Bouguen G, Peyrin-Biroulet L. Surgery for adult Crohn’s disease: what is the actual risk? Gut. 2011;60(9):1178–81.

    Article  PubMed  Google Scholar 

  4. Langholz E, Munkholm P, Davidsen MBV. Course of ulcerative colitis: analysis of changes in disease activity over years. Gastroenterology. 1994;107(1):3–11.

    Article  CAS  PubMed  Google Scholar 

  5. Colombel JF, Sandborn WJ, Reinisch W, Mantzaris GJ, Kornbluth A, Rachmilewitz D, et al. Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med. 2010;362(15):1383–95.

    Article  CAS  PubMed  Google Scholar 

  6. Panaccione R, Ghosh S, Middleton S, Marquez JR, Scott BB, Flint L, et al. Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis. Gastroenterology. 2014;146(2):392–400.e3.

    Article  CAS  PubMed  Google Scholar 

  7. Schnitzler F, Fidder H, Ferrante M, Noman M, Arijs I, Van Assche G, et al. Mucosal healing predicts long-term outcome of maintenance therapy with infliximab in Crohn’s disease. Inflamm Bowel Dis. 2009;15(9):1295–301.

    Article  PubMed  Google Scholar 

  8. Rutgeerts P, Van Assche G, Sandborn WJ, Wolf DC, Geboes K, Colombel JF, et al. Adalimumab induces and maintains mucosal healing in patients with Crohn’s disease: data from the EXTEND trial. Inflamm Bowel Dis Monit. 2012;12(4):151–2.

    Google Scholar 

  9. Allez M, Lémann M. Role of endoscopy in predicting the disease course in inflammatory bowel disease. World J Gastroenterol. 2010;16(21):2626–32.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Laharie D, Filippi J, Roblin X, Nancey S, Chevaux JB, Hébuterne X, et al. Impact of mucosal healing on long-term outcomes in ulcerative colitis treated with infliximab: a multicenter experience. Aliment Pharmacol Ther. 2013;37(10):998–1004.

    Article  CAS  PubMed  Google Scholar 

  11. Orlando A, Guglielmi FW, Cottone M, Orlando E, Romano C, Sinagra E. Clinical implications of mucosal healing in the management of patients with inflammatory bowel disease. Dig Liver Dis. 2013;45(12):986–91.

    Article  PubMed  Google Scholar 

  12. Torres J, Boyapati RK, Kennedy NA, Louis E, Colombel JF, 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.

    Article  CAS  PubMed  Google Scholar 

  13. Targan SR, Hanauer SB, van Deventer SJ, Mayer L, Present DH, Braakman T, 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. 1997;337(15):1029–35.

    Article  CAS  PubMed  Google Scholar 

  14. Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet. 2002;359(9317):1541–9.

    Article  CAS  PubMed  Google Scholar 

  15. Rutgeerts P, Sandborn W, Reagan BG, Reinisch W, Olson A, Johanns J, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353(23):2462–76.

    Article  CAS  PubMed  Google Scholar 

  16. Stidham RW, Lee TCH, Higgins PDR, Deshpande AR, Sussman DA, Singal AG, et al. Systematic review with network meta-analysis: the efficacy of anti-tumour necrosis factor-alpha agents for the treatment of Crohn’s disease. Aliment Pharmacol Ther. 2014;39(7):660–71.

    Article  CAS  PubMed  Google Scholar 

  17. Stidham RW, Lee TCH, Higgins PDR, Deshpande AR, Sussman DA, Singal AG, et al. Systematic review with network meta-analysis: the efficacy of anti-tumour necrosis factor-alpha agents for the treatment of ulcerative colitis. Aliment Pharmacol Ther. 2014;39(7):660–71.

    Article  CAS  PubMed  Google Scholar 

  18. Feagan BG, McDonald JWD, Panaccione R, Enns RA, Bernstein CN, Ponich TP, et al. Methotrexate in combination with infliximab is no more effective than infliximab alone in patients with Crohn’s disease. Gastroenterology. 2014;146(3):681–8.e1.

    Article  CAS  PubMed  Google Scholar 

  19. D’Haens G, Baert F, van Assche G, Caenepeel P, Vergauwe P, Tuynman H, et al. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn’s disease: an open randomised trial. Lancet. 2008;371(9613):660–7.

    Article  PubMed  Google Scholar 

  20. Khanna R, Bressler B, Levesque BG, Zou G, Stitt LW, Greenberg GR, et al. Early combined immunosuppression for the management of Crohn’s disease (REACT): a cluster randomised controlled trial. Lancet. 2015;386(10006):1825–34.

    Article  PubMed  Google Scholar 

  21. Jones J, Panaccione R, Russell ML, Hilsden R. Medical management of inflammatory bowel disease among Canadian gastroenterologists. Can J Gastroenterol. 2011;25(10):565–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Blackmore L, Harris A. A prospective study of infliximab withdrawal after 12 months of treatment in patients with Crohn’s disease: how will NICE guidance affect patient care? Clin Med (Northfield Il). 2012;12(3):235–8.

    Article  CAS  Google Scholar 

  23. Rutgeerts P, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, et al. Comparison of scheduled and episodic treatment strategies of infliximab in Crohn’s disease. Gastroenterology. 2004;126(2):402–13.

    Article  CAS  PubMed  Google Scholar 

  24. Van Assche G, Vermeire S, Ballet V, Gabriels F, Noman M, D’Haens G, et al. Switch to adalimumab in patients with Crohn’s disease controlled by maintenance infliximab: prospective randomised SWITCH trial. Inflamm Bowel Dis Monit. 2012;12(4):150.

    Google Scholar 

  25. Duron C, Goutte M, Pereira B, Bommelaer G, Buisson A. Factors influencing acute infusion reactions in inflammatory bowel disease patients treated with infliximab in the era of scheduled maintenance therapy. Eur J Gastroenterol Hepatol. 2015;27(6):705–11.

    Article  CAS  PubMed  Google Scholar 

  26. Shah ED, Siegel CA, Chong K, Melmed GY. Evaluating study withdrawal among biologics and immunomodulators in treating ulcerative colitis: a meta-analysis of controlled clinical trials. Inflamm Bowel Dis. 2016;22(4):933–9.

    Article  PubMed  Google Scholar 

  27. Colombel JF, Loftus EV, Tremaine WJ, Egan LJ, Harmsen WS, Schleck CD, et al. The safety profile of infliximab in patients with Crohn’s disease: the mayo clinic experience in 500 patients. Gastroenterology. 2004;126(1):19–31.

    Article  CAS  PubMed  Google Scholar 

  28. Seiderer J, Göke B, Ochsenkühn T. Safety aspects of infliximab in inflammatory bowel disease patients: a retrospective cohort study in 100 patients of a German University Hospital. Digestion. 2004;70(1):3–9.

    Article  CAS  PubMed  Google Scholar 

  29. Lichtenstein GR, Feagan BG, Cohen RD, Salzberg BA, Diamond RH, Price S, et al. Serious infection and mortality in patients with Crohn’s disease: more than 5 years of follow-up in the TREAT™ registry. Am J Gastroenterol. 2012;107(9):1409–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Sousa P, Allez M. Complications of biologics in inflammatory bowel disease. Curr Opin Gastroenterol. 2015;31(4):296–302.

    Article  CAS  PubMed  Google Scholar 

  31. Rahier JF, Magro F, Abreu C, Armuzzi A, Ben-Horin S, Chowers Y, et al. Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis. 2014;8(6):443–68.

    Article  CAS  PubMed  Google Scholar 

  32. Lichtenstein GR, Feagan BG, Cohen RD, Salzberg BA, Diamond RH, Langholff W, et al. Drug therapies and the risk of malignancy in Crohn’s disease: results from the TREAT™ Registry. Am J Gastroenterol. 2014;109(2):212–23.

    Article  CAS  PubMed  Google Scholar 

  33. Williams CJ, Peyrin-Biroulet L, Ford A. Systematic review with meta-analysis: malignancies with anti-tumour necrosis factor-α therapy in inflammatory bowel disease. Aliment Pharmacol Ther. 2014;39(5):447–58.

    Article  CAS  PubMed  Google Scholar 

  34. Dulai PS, Thompson KD, Blunt HB, Dubinsky MC, Siegel CA. Risks of serious infection or lymphoma with anti-tumor necrosis factor therapy for pediatric inflammatory bowel disease: a systematic review. Clin Gastroenterol Hepatol. 2014;12(9):1443–51.

    Article  PubMed  Google Scholar 

  35. Annese V, Beaugerie L, Egan L, Biancone L, Bolling C, Brandts C, et al. European evidence-based consensus: Inflammatory bowel disease and malignancies. J Crohns Colitis. 2015;9(11):945–65.

    Article  PubMed  Google Scholar 

  36. Jeuring SFG, van den Heuvel TRA, Zeegers MP, Hameeteman WH, Romberg-Camps MJL, Oostenbrug LE, et al. Epidemiology and long-term outcome of inflammatory bowel disease diagnosed at elderly age-an increasing distinct entity? Inflamm Bowel Dis. 2016;22(6):1425–34.

    Article  PubMed  Google Scholar 

  37. Bernstein CN, Longobardi T, Finlayson G, Blanchard JF. Direct medical cost of managing IBD patients: a Canadian population-based study. Inflamm Bowel Dis. 2012;18(8):1498–508.

    Article  PubMed  Google Scholar 

  38. Loomes DE, Teshima C, Jacobs P, Fedorak RN. Health care resource use and costs in Crohn’s disease before and after infliximab therapy. Can J Gastroenterol. 2011;25(9):497–502.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Park KT, Colletti RB, Rubin DT, Sharma BK, Thompson A, Krueger A. Health insurance paid costs and drivers of costs for patients with Crohn’s disease in the United States. Am J Gastroenterol. 2016;111(1):15–23.

    Article  CAS  PubMed  Google Scholar 

  40. Gisbert JP, Marín AC, Chaparro M. The risk of relapse after anti-TNF discontinuation in inflammatory bowel disease: systematic review and meta-analysis. Am J Gastroenterol. 2016;111(5):632–47.

    Article  CAS  PubMed  Google Scholar 

  41. Louis E, Mary JY, Vernier-Massouille G, Grimaud JC, Bouhnik Y, Laharie D, et al. Maintenance of remission among patients with Crohn’s disease on antimetabolite therapy after infliximab therapy is stopped. Gastroenterology. 2012;142(1):63–70.

    Article  CAS  PubMed  Google Scholar 

  42. Domènech E, Hinojosa J, Nos P, Garcia-Planella E, Cabré E, Bernal I, 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.

    Article  PubMed  Google Scholar 

  43. Molnár T, Lakatos PL, Farkas K, Nagy F, Szepes Z, Miheller P, et al. Predictors of relapse in patients with Crohn’s disease in remission after 1 year of biological therapy. Aliment Pharmacol Ther. 2013;37(2):225–33.

    Article  PubMed  Google Scholar 

  44. Ampuero J, Rojas-Feria M, Castro-Fernandez M, Millan-Lorenzo M, Guerrero-Jimenez P, Romero-Gomez M. Remission maintained by monotherapy after biological + immunosuppressive combination for Crohn’s disease in clinical practice. J Gastroenterol Hepatol. 2015;31:112–8.

    Article  Google Scholar 

  45. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Cabré E, Domènech E. Impact of environmental and dietary factors on the course of inflammatory bowel disease. World J Gastroenterol. 2012;18(29):3814–22.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Papamichael K, Vermeire S. Withdrawal of anti-tumour necrosis factor α therapy in inflammatory bowel disease. World J Gastroenterol. 2015;21(16):4773.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Tozer P, Ng SC, Siddiqui MR, Plamondon S, Burling D, Gupta A, et al. Long-term MRI-guided combined anti-TNF-a and thiopurine therapy for crohn’s perianal fistulas. Inflamm Bowel Dis. 2012;18(10):1825–34.

    Article  PubMed  Google Scholar 

  49. 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.

    CAS  Google Scholar 

  50. De Cruz P, Kamm MA, Hamilton AL, Ritchie KJ, Krejany EO, Gorelik A, 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.

    Article  PubMed  Google Scholar 

  51. Sachar DB, Lemmer E, Ibrahim C, Edden Y, Ullman T, Ciardulo J, et al. Recurrence patterns after first resection for stricturing or penetrating Crohn’s disease. Inflamm Bowel Dis. 2009;15(7):1071–5.

    Article  PubMed  Google Scholar 

  52. 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 Crohns Colitis. 2015:1–7. [Epub ahead of print].

    Google Scholar 

  53. Molnár T, Farkas K, Miheller P, Nyári T, Szepes Z, Herszényi L, Müzes G, Nagy F, Tulassay ZWT. Is the efficacy of successful infliximab induction therapy maintained for one year lasting without retreatment in different behavior types of Crohn’s disease? J Crohns Colitis. 2008;2(4):322–6.

    Article  PubMed  Google Scholar 

  54. Waugh AWG, Garg S, Matic K, Gramlich L, Wong C, Sadowski DC, 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.

    Article  CAS  PubMed  Google Scholar 

  55. Armuzzi A, Marzo M, Felice C, De Vincentis F, Andrisani G, Mocci G, et al. W1288 long-term scheduled therapy with infliximab in inflammatory bowel disease: a single-centre observational study. Gastroenterology. 2010;138(5):S691–2.

    Google Scholar 

  56. Molander P, Färkkilä M, Ristimäki A, Salminen K, Kemppainen H, Blomster T, 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. 2015;9(1):33–40.

    PubMed  Google Scholar 

  57. Steenholdt C, Molazahi A, Ainsworth MA, Brynskov J, Thomsen OØ, Seidelin JB. Outcome after discontinuation of infliximab in patients with inflammatory bowel disease in clinical remission: an observational Danish single center study. Scand J Gastroenterol. 2012;47(5):518–27.

    Article  CAS  PubMed  Google Scholar 

  58. Rismo R, Olsen T, Cui G, Paulssen EJ, Christiansen I, Johnsen K, et al. Normalization of mucosal cytokine gene expression levels predicts long-term remission after discontinuation of anti-TNF therapy in Crohn’s disease. Scand J Gastroenterol. 2013;48(3):311–9.

    Article  CAS  PubMed  Google Scholar 

  59. Olsen T, Rismo R, Gundersen MD, Paulssen EJ, Johnsen K, Kvamme J-M, et al. Normalization of mucosal tumor necrosis factor-α: a new criterion for discontinuing infliximab therapy in ulcerative colitis. Cytokine. 2016;79:90–5.

    Article  CAS  PubMed  Google Scholar 

  60. Casanova MJ, Chaparro M, García-Sánchez V, Nantes O, Jáuregui-Amezaga A, Rojas-Feria M, et al. Tu1926 Evolution After Anti-TNF Drug Discontinuation in Patients With Inflammatory Bowel Disease (IBD): A Multicenter Long-Term Follow-Up. Gastroenterology. 2016;150(4):S979.

    Google Scholar 

  61. Groupe d’Etude Therapeutique des Affections Inflammatoires Digestives. A proSpective Randomized Controlled Trial comParing infliximAb-antimetabolites Combination Therapy to Anti-metabolites monotheRapy and Infliximab monothErapy in Crohn’s Disease Patients in Sustained Steroid-free Remission on Combination Therapy (SPARE). Last Updated Date Nov 20, 2015. Available from URL https://clinicaltrials.gov/ct2/show/record/NCT02177071?term=spare&rank=3.

  62. Drobne D, Bossuyt P, Breynaert C, Cattaert T, Vande Casteele N, Compernolle G, et al. Withdrawal of immunomodulators after co-treatment does not reduce trough level of infliximab in patients with crohn’s disease. Clin Gastroenterol Hepatol. 2015;13(3):514–21.

    Article  CAS  PubMed  Google Scholar 

  63. Ben-Horin S, Chowers Y, Ungar B, Kopylov U, Loebstein R, Weiss B, et al. Undetectable anti-TNF drug levels in patients with long-term remission predict successful drug withdrawal. Aliment Pharmacol Ther. 2015;42(3):356–64.

    Article  CAS  PubMed  Google Scholar 

  64. Chauvin A, Le Thuaut A, Belhassan M, Le Baleur Y, Mesli F, Bastuji-Garin S, et al. Infliximab as a bridge to remission maintained by antimetabolite therapy in Crohn’s disease: a retrospective study. Dig Liver Dis. 2014;46(8):695–700.

    Article  CAS  PubMed  Google Scholar 

  65. Ordas I, Feagan BG, Sandborn WJ. Early use of immunosuppressives or TNF antagonists for the treatment of Crohn’s disease: time for a change. Gut. 2011;60:1754–63.

    Article  CAS  PubMed  Google Scholar 

  66. Papamichael K, Vande Casteele N, Gils A, Tops S, Hauenstein S, Singh S, et al. Long-term outcome of patients with Crohn’s disease who discontinued infliximab therapy upon clinical remission. Clin Gastroenterol Hepatol. 2015;13(6):1103–10.

    Article  PubMed  Google Scholar 

  67. 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. Inflamm Bowel Dis. 2014;20(6):1021–8.

    PubMed  Google Scholar 

  68. Sorrentino D, Nash P, Viladomiu M, Hontecillas R, Bassaganya-Riera J. Stopping anti-TNF agents in patients with Crohn’s disease in remission: is it a feasible long-term strategy? Inflamm Bowel Dis. 2014;20(4):757–66.

    Article  PubMed  Google Scholar 

  69. Vuitton L, Marteau P, Sandborn WJ, Levesque BG, Feagan B, Vermeire S, et al. IOIBD technical review on endoscopic indices for Crohn’s disease clinical trials. Gut. 2016;65(9):1447–55.

    Google Scholar 

  70. Barreiro-de Acosta M, Vallejo N, De La Iglesia D, Uribarri L, Baston I, Ferreiro-Iglesias R, et al. Evaluation of the risk of relapse in ulcerative colitis according to the degree of mucosal healing (Mayo 0 vs 1): a longitudinal cohort study. J Crohns Colitis. 2016;10(1):13–9.

    Article  PubMed  Google Scholar 

  71. Pittet V, Froehlich F, Maillard MH, Mottet C, Gonvers JJ, Felley C, et al. When do we dare to stop biological or immunomodulatory therapy for Crohn’s disease? Results of a multidisciplinary European expert panel. J Crohns Colitis. 2013;7(10):820–6.

    Article  PubMed  Google Scholar 

  72. Sorrentino D, Paviotti A, Terrosu G, Avellini C, Geraci M, Zarifi D. Low-dose maintenance therapy with infliximab prevents postsurgical recurrence of Crohn’s disease. Clin Gastroenterol Hepatol. 2010;8(7):591–9.e1.

    Article  CAS  PubMed  Google Scholar 

  73. Mantzaris GJ, Karatzas P, Kyriakos N, Archavlis EJ, Papamichael K, Tzannetakou X, et al. Sa1270 can we increase the dose interval of infliximab to 10 weeks without risking loss of response in patients with Crohn’s disease? Prospective, single-center pilot study based on successive measurements of fecal calprotectin. Gastroenterology. 2014;146(5):S–248.

    Article  Google Scholar 

  74. van Herwaarden N, den Broeder AA, Jacobs W, van der Maas A, Bijlsma JW, van Vollenhoven RF, van den Bemt BJ. Down-titration and discontinuation strategies of tumor necrosis factor-blocking agents for rheumatoid arthritis in patients with low disease activity. Cochrane Database Syst Rev. 2014;9:CD010455.

    Google Scholar 

  75. Vande Casteele N, Ferrante M, Van Assche G, Ballet V, Compernolle G, Van Steen K, et al. Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease. Gastroenterology. 2015;148(7):1320–9.e3.

    Article  CAS  PubMed  Google Scholar 

  76. D’Haens G, Vermeire S, Lambrecht G, Baert F, Bossuyt P, Nachury M, et al. OP029 Drug-concentration versus symptom-driven dose adaptation of Infliximab in patients with active Crohn’s disease: a prospective, randomised, multicentre trial (Tailorix). J Crohns Colitis. 2016;10(Suppl 1):s24.

    Google Scholar 

  77. Reenaers C, Mary J-Y, Nachury M, Bouhnik Y, Laharie D, Allez M, et al. 313 Long-term outcome after infliximab withdrawal for sustained remission in Crohn’s disease. Gastroenterology. 2016;150(4):S72.

    Article  Google Scholar 

  78. Annunziata ML, Papparella LG, Sansoni I, Balestrieri P, Cicala M. P402 Normalized wall thickness at MRE predicts clinical remission in Crohn’s disease after infliximab discontinuation: a 5 years follow-up. J Crohns Colitis. 2014;8:S233.

    Article  Google Scholar 

  79. Ramos L, Hernandez Camba A, Carrillo Palau M, Alonso I, Hernandez Alvarez-Buylla N, Quintero Carrion E. P398 Outcome of treatment with biological agents in Crohn’s disease: 117 patients in 5 years from a tertiary referral center. J Crohns Colitis. 2014;8:S231.

    Article  Google Scholar 

  80. Farkas K, Lakatos PL, Nagy F, Szepes Z, Miheller P, Papp M, et al. Predictors of relapse in patients with ulcerative colitis in remission after one-year of infliximab therapy. Scand J Gastroenterol. 2013;48(12):1394–8.

    Article  CAS  PubMed  Google Scholar 

  81. Muñoz Villafranca C, Bravo Rodríguez MT, Ortiz de Zárate J, Arreba González P, García Kamiruaga I, Heras Martín J, et al. P405 Mucosal healing in patients with ulcerative colitis treated with infliximab. What happens after treatment is discontinued? J Crohns Colitis. 2014;8:S234–5.

    Article  Google Scholar 

  82. 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;192(5):1355–9.

    Google Scholar 

  83. Bortlik M, Duricova D, Machkova N, Hruba V, Lukas M, Mitrova K, et al. Discontinuation of anti-tumor necrosis factor therapy in inflammatory bowel disease patients: a prospective observation. Scand J Gastroenterol. 2016;51(2):196–202.

    Article  CAS  PubMed  Google Scholar 

  84. Hlavaty T, Krajcovicova A, Letkovsky J, Sturdik I, Koller T, Toth JHM. Relapse rates of inflammatory bowel disease patients in deep and clinical remission after discontinuing anti-tumor necrosis factor alpha therapy. Bratisl Lek Listy. 2016;117(4):205–11.

    CAS  PubMed  Google Scholar 

  85. Caviglia R, Ribolsi M, Rizzi M, Emerenziani S, Annunziata ML, Cicala M. Maintenance of remission with infliximab in inflammatory bowel disease: efficacy and safety long-term follow-up. World J Gastroenterol. 2007;13(39):5238–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Ciria V, Silva P, Leo E, Trigo C, De la Cruz MD, Herrera JM, et al. P487 Factors influencing recurrence following suspension of biological treatment. Importance of mucosal healing. J Crohns Colitis. 2014;8:S270.

    Article  Google Scholar 

  87. Farkas K, Lakatos PL, Szűcs M, Pallagi-Kunstár É, Bálint A, Nagy F, Szepes Z, Vass N, Kiss LS, Wittmann TMT. Frequency and prognostic role of mucosal healing in patients with Crohn’s disease and ulcerative colitis after one-year of biological therapy. World J Gastroenterol. 2014;20(11):2995–3001.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Luppino I, Spagnuolo R, Marasco R, Cosco C, Ruggiero G, Cosco V, et al. P.02.11 Withdrawal of infliximab (Ifx) after achieving remission: outcome in a cohort of inflammatory bowel disease (Ibd) patients. Dig Liver Dis. 2013;45(2013):S100–1.

    Article  Google Scholar 

  89. Marino M, Zucchi E, Fabbro M, Lodolo I, Maieron R, Vadalà S, et al. P401 Outcome of infliximab discontinuation in IBD patients and therapy rechallenging in relapsers: single centre preliminary data. J Crohns Colitis. 2014;8:S232–3.

    Article  Google Scholar 

  90. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Vande Casteele N, Khanna R, Levesque BG, Stitt L, Zou GY, Singh S, et al. The relationship between infliximab concentrations, antibodies to infliximab and disease activity in Crohn’s disease. Gut. 2015;64(10):1539–45.

    Article  CAS  PubMed  Google Scholar 

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CHS: Consultant for Janssen, AbbVie, Shire, Takeda, Actavis, and Ferring; Speaker for Janssen and AbbVie

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, AB, Canada

    Hang Hock Shim & Cynthia H. Seow

  2. Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada

    Cynthia H. Seow

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  1. Hang Hock Shim
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  2. Cynthia H. Seow
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Correspondence to Cynthia H. Seow .

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Editors and Affiliations

  1. Beth Israel Deaconess Medical Center Center for Inflammatory Bowel Disease, Harvard Medical School, Boston, Massachusetts, USA

    Adam S. Cheifetz

  2. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

    Joseph D. Feuerstein

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Shim, H.H., Seow, C.H. (2018). Cessation of Biologics: Can It Be Done?. In: Cheifetz, A., Feuerstein, J. (eds) Treatment of Inflammatory Bowel Disease with Biologics . Springer, Cham. https://doi.org/10.1007/978-3-319-60276-9_10

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  • DOI: https://doi.org/10.1007/978-3-319-60276-9_10

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-60275-2

  • Online ISBN: 978-3-319-60276-9

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