Management of inflammatory bowel disease in poor responders to infliximab

Iván Guerra, Fernando Bermejo, Iván Guerra, Fernando Bermejo

Abstract

Infliximab (IFX) is an effective treatment for inducing and maintaining response in Crohn's disease and ulcerative colitis patients. Some patients present lack of response or loss of response to IFX during maintenance therapy. Empirical management with combination therapy with an immunomodulator, IFX dose escalation, or switching IFX for another antitumor necrosis factor-α drug, mainly adalimumab, is common in clinical practice. Selecting the best choice with the help of serum drug concentrations and trough IFX antibody concentrations could be a very interesting approach. In addition to surgery, a broad spectrum of new drugs has been tested and could expand treatment options in the near future.

Keywords: Crohn’s disease; anti-TNF; inflammatory bowel disease; infliximab; treatment; ulcerative colitis.

References

    1. Terdiman JP, Gruss CB, Heidelbaugh JJ, et al. American Gastroenterological Association Institute guideline on the use of thiopurines, methotrexate, and anti-TNF-alpha biologic drugs for the induction and maintenance of remission in inflammatory Crohn’s disease. Gastroenterology. 2013;145(6):1459–1463.
    1. Stidham RW, Lee TC, Higgins PD, 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):660–671.
    1. Reinisch W, Van Assche G, Befrits R, et al. Recommendations for the treatment of ulcerative colitis with infliximab: a gastroenterology expert group consensus. J Crohns Colitis. 2012;6(2):248–258.
    1. Dignass A, Lindsay JO, Sturm A, et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 2: current management. J Crohns Colitis. 2012;6(10):991–1030.
    1. Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353(23):2462–2476.
    1. Gisbert JP, Gonzalez-Lama Y, Mate J. Systematic review: infliximab therapy in ulcerative colitis. Aliment Pharmacol Ther. 2007;25(1):19–37.
    1. Dignass A, Van Assche G, Lindsay JO, et al. The second European evidence-based consensus on the diagnosis and management of Crohn’s disease: current management. J Crohns Colitis. 2010;4(1):28–62.
    1. Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet. 2002;359(9317):1541–1549.
    1. Gisbert JP, Panes J. Loss of response and requirement of infliximab dose intensification in Crohn’s disease: a review. Am J Gastroenterol. 2009;104(3):760–767.
    1. Steenholdt C, Palarasah Y, Bendtzen K, et al. Pre-existing IgG antibodies cross-reacting with the Fab region of infliximab predict efficacy and safety of infliximab therapy in inflammatory bowel disease. Aliment Pharmacol Ther. 2013;37(12):1172–1183.
    1. Sprakes MB, Ford AC, Warren L, Greer D, Hamlin J. Efficacy, tolerability, and predictors of response to infliximab therapy for Crohn’s disease: a large single centre experience. J Crohns Colitis. 2012;6(2):143–153.
    1. De Vos M, Louis EJ, Jahnsen J, et al. Consecutive fecal calprotectin measurements to predict relapse in patients with ulcerative colitis receiving infliximab maintenance therapy. Inflamm Bowel Dis. 2013;19(10):2111–2117.
    1. Laharie D, Mesli S, El Hajbi F, et al. Prediction of Crohn’s disease relapse with faecal calprotectin in infliximab responders: a prospective study. Aliment Pharmacol Ther. 2011;34(4):462–469.
    1. Molander P, af Bjorkesten CG, Mustonen H, et al. Fecal calprotectin concentration predicts outcome in inflammatory bowel disease after induction therapy with TNFalpha blocking agents. Inflamm Bowel Dis. 2012;18(11):2011–2017.
    1. 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-alpha therapy. Aliment Pharmacol Ther. 2011;34(1):1–10.
    1. Maser EA, Villela R, Silverberg MS, Greenberg GR. Association of trough serum infliximab to clinical outcome after scheduled maintenance treatment for Crohn’s disease. Clin Gastroenterol Hepatol. 2006;4(10):1248–1254.
    1. Seow CH, Newman A, Irwin SP, Steinhart AH, Silverberg MS, Greenberg GR. Trough serum infliximab: a predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis. Gut. 2010;59(1):49–54.
    1. Cornillie F, Hanauer SB, Diamond RH, et al. Postinduction serum infliximab trough level and decrease of C-reactive protein level are associated with durable sustained response to infliximab: a retrospective analysis of the ACCENT I trial. Gut. 2014 Jan 28; Epub.
    1. O’Meara S, Nanda KS, Moss AC. Antibodies to infliximab and risk of infusion reactions in patients with inflammatory bowel disease: a systematic review and meta-analysis. Inflamm Bowel Dis. 2014;20(1):1–6.
    1. Van Assche G, Magdelaine-Beuzelin C, D’Haens G, et al. Withdrawal of immunosuppression in Crohn’s disease treated with scheduled infliximab maintenance: a randomized trial. Gastroenterology. 2008;134(7):1861–1868.
    1. Nanda KS, Cheifetz AS, Moss AC. Impact of Antibodies to Infliximab on Clinical Outcomes and Serum Infliximab Levels in Patients With Inflammatory Bowel Disease (IBD): A Meta-Analysis. Am J Gastroenterol. 2013;108(1):40–47.
    1. Guerra I, Chaparro M, Bermejo F, Gisbert JP. Utility of measuring serum concentrations of anti-TNF agents and anti-drug antibodies in inflammatory bowel disease. Curr Drug Metab. 2011;12(6):594–598.
    1. Eser A, Primas C, Reinisch W. Drug monitoring of biologics in inflammatory bowel disease. Curr Opin Gastroenterol. 2013;29(4):391–396.
    1. Vande Casteele N, Gils A, Singh S, et al. Antibody response to infliximab and its impact on pharmacokinetics can be transient. Am J Gastroenterol. 2013;108(6):962–971.
    1. Dirks NL, Meibohm B. Population pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet. 2010;49(10):633–659.
    1. Fasanmade AA, Adedokun OJ, Olson A, Strauss R, Davis HM. Serum albumin concentration: a predictive factor of infliximab pharmacokinetics and clinical response in patients with ulcerative colitis. Int J Clin Pharmacol Ther. 2010;48(5):297–308.
    1. Ainsworth MA, Bendtzen K, Brynskov J. Tumor necrosis factor-alpha binding capacity and anti-infliximab antibodies measured by fluid-phase radioimmunoassays as predictors of clinical efficacy of infliximab in Crohn’s disease. Am J Gastroenterol. 2008;103(4):944–948.
    1. Arijs I, Li K, Toedter G, et al. Mucosal gene signatures to predict response to infliximab in patients with ulcerative colitis. Gut. 2009;58(12):1612–1619.
    1. Arijs I, Quintens R, Van Lommel L, et al. Predictive value of epithelial gene expression profiles for response to infliximab in Crohn’s disease. Inflamm Bowel Dis. 2010;16(12):2090–2098.
    1. Farrell RJ, Alsahli M, Jeen YT, Falchuk KR, Peppercorn MA, Michetti P. Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn’s disease: a randomized controlled trial. Gastroenterology. 2003;124(4):917–924.
    1. Mantzaris GJ, Viazis N, Petraki K, et al. A pilot study comparing hydrocortisone premedication to concomitant azathioprine treatment in preventing loss of response to infliximab. Eur J Gastroenterol Hepatol. 2009;21(9):1042–1048.
    1. Lofberg R, Louis EV, Reinisch W, et al. Adalimumab produces clinical remission and reduces extraintestinal manifestations in Crohn’s disease: results from CARE. Inflamm Bowel Dis. 2012;18(1):1–9.
    1. Ho GT, Mowat A, Potts L, et al. Efficacy and complications of adalimumab treatment for medically-refractory Crohn’s disease: analysis of nationwide experience in Scotland (2004–2008) Aliment Pharmacol Ther. 2009;29(5):527–534.
    1. Panaccione R, Loftus EV, Jr, Binion D, et al. Efficacy and safety of adalimumab in Canadian patients with moderate to severe Crohn’s disease: results of the Adalimumab in Canadian SubjeCts with ModErate to Severe Crohn’s DiseaSe (ACCESS) trial. Can J Gastroenterol. 2011;25(8):419–425.
    1. Colombel JF, Sandborn WJ, Reinisch W, et al. Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med. 2010;362(15):1383–1395.
    1. Panaccione R, Ghosh S, Middleton S, et al. Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis. Gastroenterology. 2014;146(2):392–400.
    1. Mackey AC, Green L, Liang LC, Dinndorf P, Avigan M. Hepatosplenic T cell lymphoma associated with infliximab use in young patients treated for inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2007;44(2):265–267.
    1. Deepak P, Stobaugh DJ, Ehrenpreis ED. Infectious complications of TNF-alpha inhibitor monotherapy versus combination therapy with immunomodulators in inflammatory bowel disease: analysis of the Food and Drug Administration Adverse Event Reporting System. J Gastrointestin Liver Dis. 2013;22(3):269–276.
    1. Siegel CA, Finlayson SR, Sands BE, Tosteson AN. Adverse events do not outweigh benefits of combination therapy for Crohn’s disease in a decision analytic model. Clin Gastroenterol Hepatol. 2012;10(1):46–51.
    1. Feagan BG, McDonald JW, Panaccione R, et al. Methotrexate in combination with infliximab is no more effective than infliximab alone in patients with Crohn’s disease. Gastroenterology. 2014;146(3):e681–e688.
    1. McDonald JW, Tsoulis DJ, Macdonald JK, Feagan BG. Methotrexate for induction of remission in refractory Crohn’s disease. Cochrane Database Syst Rev. 2012;12:CD003459.
    1. Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med. 2004;350(9):876–885.
    1. Regueiro M, Siemanowski B, Kip KE, Plevy S. Infliximab dose intensification in Crohn’s disease. Inflamm Bowel Dis. 2007;13(9):1093–1099.
    1. Schnitzler F, Fidder H, Ferrante M, et al. Long-term outcome of treatment with infliximab in 614 patients with Crohn’s disease: results from a single-centre cohort. Gut. 2009;58(4):492–500.
    1. Hyams J, Crandall W, Kugathasan S, et al. Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn’s disease in children. Gastroenterology. 2007;132(3):863–873. quiz 1165–1166.
    1. Chaparro M, tinez-Montiel P, Van Domselaar M, et al. Intensification of infliximab therapy in Crohn’s disease: efficacy and safety. J Crohns Colitis. 2012;6(1):62–67.
    1. Kopylov U, Mantzaris GJ, Katsanos KH, et al. The efficacy of shortening the dosing interval to once every six weeks in Crohn’s patients losing response to maintenance dose of infliximab. Aliment Pharmacol Ther. 2011;33(3):349–357.
    1. Rostholder E, Ahmed A, Cheifetz AS, Moss AC. Outcomes after escalation of infliximab therapy in ambulatory patients with moderately active ulcerative colitis. Aliment Pharmacol Ther. 2012;35(5):562–567.
    1. Cesarini M, Katsanos K, Papamichael K, et al. Dose optimization is effective in ulcerative colitis patients losing response to infliximab: a collaborative multicentre retrospective study. Dig Liver Dis. 2014;46(2):135–139.
    1. Steenholdt C, Brynskov J, Thomsen OO, et al. Individualised therapy is more cost-effective than dose intensification in patients with Crohn’s disease who lose response to anti-TNF treatment: a randomised, controlled trial. Gut. 2014;63(6):919–927.
    1. Sandborn WJ, Hanauer S, Loftus EV, Jr, et al. An open-label study of the human anti-TNF monoclonal antibody adalimumab in subjects with prior loss of response or intolerance to infliximab for Crohn’s disease. Am J Gastroenterol. 2004;99(10):1984–1989.
    1. Papadakis KA, Shaye OA, Vasiliauskas EA, et al. Safety and efficacy of adalimumab (D2E7) in Crohn’s disease patients with an attenuated response to infliximab. Am J Gastroenterol. 2005;100(1):75–79.
    1. Sandborn WJ, Rutgeerts P, Enns R, et al. Adalimumab induction therapy for Crohn disease previously treated with infliximab: a randomized trial. Ann Intern Med. 2007;146(12):829–838.
    1. Colombel JF, Sandborn WJ, Rutgeerts P, et al. Adalimumab for Maintenance of Clinical Response and Remission in Patients With Crohn’s Disease: The CHARM Trial. Gastroenterology. January. 2007;132(1):52–65.
    1. Karmiris K, Paintaud G, Noman M, et al. Influence of trough serum levels and immunogenicity on long-term outcome of adalimumab therapy in Crohn’s disease. Gastroenterology. 2009;137(5):1628–1640.
    1. Ma C, Panaccione R, Heitman SJ, Devlin SM, Ghosh S, Kaplan GG. Systematic review: the short-term and long-term efficacy of adalimumab following discontinuation of infliximab. Aliment Pharmacol Ther. 2009;30(10):977–986.
    1. Taxonera C, Estelles J, Fernandez-Blanco I, et al. Adalimumab induction and maintenance therapy for patients with ulcerative colitis previously treated with infliximab. Aliment Pharmacol Ther. 2011;33(3):340–348.
    1. Kaplan GG, Hur C, Korzenik J, Sands BE. Infliximab dose escalation vs initiation of adalimumab for loss of response in Crohn’s disease: a cost-effectiveness analysis. Aliment Pharmacol Ther. 2007;26(11–12):1509–1520.
    1. Lichtiger S, Binion DG, Wolf DC, et al. The CHOICE trial: adalimumab demonstrates safety, fistula healing, improved quality of life and increased work productivity in patients with Crohn’s disease who failed prior infliximab therapy. Aliment Pharmacol Ther. 2010;32(10):1228–1239.
    1. Louis E, Lofberg R, Reinisch W, et al. Adalimumab improves patient-reported outcomes and reduces indirect costs in patients with moderate to severe Crohn’s disease: results from the CARE trial. J Crohns Colitis. 2013;7(1):34–43.
    1. Sandborn WJ, Abreu MT, D’Haens G, et al. Certolizumab pegol in patients with moderate to severe Crohn’s disease and secondary failure to infliximab. Clin Gastroenterol Hepatol. 2010;8(8):688–695.
    1. Baert F, Drobne D, Gils A, et al. Early trough levels and antibodies to infliximab predict safety and success of re-initiation of infliximab therapy. Clin Gastroenterol Hepatol. 2014 Jan 29; Epub.
    1. Sandborn WJ, Feagan BG, ano C, et al. Subcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014;146(1):96–109.
    1. Targan SR, Feagan BG, Fedorak RN, et al. Natalizumab for the treatment of active Crohn’s disease: results of the ENCORE trial. Gastroenterology. 2007;132(5):1672–1683.
    1. Yousry TA, Major EO, Ryschkewitsch C, et al. Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy. N Engl J Med. 2006;354(9):924–933.
    1. Lobaton T, Vermeire S, Van Assche G, Rutgeerts P. Review article: anti-adhesion therapies for inflammatory bowel disease. Aliment Pharmacol Ther. 2014;39(6):579–594.
    1. Feagan BG, Rutgeerts P, Sands BE, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013;369(8):699–710.
    1. Sandborn WJ, Feagan BG, Rutgeerts P, et al. Vedolizumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2013;369(8):711–721.
    1. Sandborn WJ, Gasink C, Gao LL, et al. Ustekinumab induction and maintenance therapy in refractory Crohn’s disease. N Engl J Med. 2012;367(16):1519–1528.
    1. Abreu MT, von Tirpitz C, Hardi R, et al. Extracorporeal photopheresis for the treatment of refractory Crohn’s disease: results of an open-label pilot study. Inflamm Bowel Dis. 2009;15(6):829–836.
    1. Hommes DW, Duijvestein M, Zelinkova Z, et al. Long-term follow-up of autologous hematopoietic stem cell transplantation for severe refractory Crohn’s disease. J Crohns Colitis. 2011;5(6):543–549.

Source: PubMed

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