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Impact of Concomitant Immunomodulator Use on Long-Term Outcomes in Patients Receiving Scheduled Maintenance Infliximab

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Abstract

The long-term benefits of combining scheduled infliximab with concomitant immunomodulators [azathioprine or 6-mercaptopurine (6-MP)] in patients with Crohn’s disease are unclear. Historical cohort followed for 5 years after initiation of infliximab for active Crohn’s disease. Data were available on 123 patients who received scheduled maintenance infliximab infusions, for up to 5 years after initiation of infliximab. Clinical remission rates in the entire cohort were 73% (82/113) at 1 year, 65% (65/100) at 2 years, and 58% (21/36) at 5 years. Remission rates with maintenance infliximab were significantly improved in those receiving concomitant immunomodulators at 1 year (86% versus 68%, P = 0.03), but not at 2 years (80% versus 72%, P = 0.4). In a multivariate logistic regression model, concomitant immunomodulator use was not associated with a significantly improved odds ratio of remission in patients on maintenance infliximab [odds ratio (OR) 1.1, 95% confidence intervals (CI) 0.9–1.2, P = 0.9]. The risk of surgery was significantly reduced in those receiving immunomodulators at the commencement of maintenance infliximab (OR 0.3, 95% CI 0.1–0.7, P = 0.01), but not in patients who continued maintenance concomitant therapy (OR 0.4, 95% CI 0.1–1.5, P = 0.1). The combination of maintenance infliximab and an immunomodulator produced modest improvements in outcomes beyond maintenance infliximab alone in this cohort.

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References

  1. Akobeng AK, Zachos M. Tumor necrosis factor-alpha antibody for induction of remission in Crohn’s disease. Cochrane Database Syst Rev. 2004;CD003574.

  2. Rutgeerts P, Van Assche G, Vermeire S. Review article: infliximab therapy for inflammatory bowel disease–seven years on. Aliment Pharmacol Ther. 2006;23:451–463. doi:10.1111/j.1365-2036.2006.02786.x.

    Article  CAS  PubMed  Google Scholar 

  3. Hanauer SB. Clinical perspectives in Crohn’s disease. Turning traditional treatment strategies on their heads: current evidence for “step-up” versus “top-down”. Rev Gastroenterol Disord. 2007;7(Suppl 2):S17–S22.

    PubMed  Google Scholar 

  4. Lichtenstein GR, Abreu MT, Cohen R, Tremaine W. American gastroenterological association institute medical position statement on corticosteroids, immunomodulators, and infliximab in inflammatory bowel disease. Gastroenterology. 2006;130:935–939. doi:10.1053/j.gastro.2006.01.047.

    Article  PubMed  Google Scholar 

  5. Travis SP, Stange EF, Lemann M, et al. European evidence based consensus on the diagnosis and management of Crohn’s disease: current management. Gut. 2006;55(Suppl 1):16–35. doi:10.1136/gut.2005.081950b.

    Article  Google Scholar 

  6. Arnott ID, McNeill G, Satsangi J. An analysis of factors influencing short-term and sustained response to infliximab treatment for Crohn’s disease. Aliment Pharmacol Ther. 2003;17:1451–1457. doi:10.1046/j.1365-2036.2003.01574.x.

    Article  CAS  PubMed  Google Scholar 

  7. Casellas F, Rodrigo L, Nino P, Pantiga C, Riestra S, Malagelada JR. Sustained improvement of health-related quality of life in Crohn’s disease patients treated with infliximab and azathioprine for 4 years. Inflamm Bowel Dis. 2007;13:1395–1400. doi:10.1002/ibd.20205.

    Article  PubMed  Google Scholar 

  8. Din S, Cochrane CJ, Noble CL, Satsangi J, Arnott ID. Combination therapy of infliximab and azathioprine reduces disease progression in Crohn’s disease. Inflamm Bowel Dis. 2007;14:143–145. doi:10.1002/ibd.20260.

    Article  Google Scholar 

  9. Mortimore M, Gibson PR, Selby WS, Radford-Smith GL, Florin TH. Early Australian experience with infliximab, a chimeric antibody against tumour necrosis factor-alpha, in the treatment of Crohn’s disease: is its efficacy augmented by steroid-sparing immunosuppressive therapy? The infliximab User Group. Intern Med J. 2001;31:146–150. doi:10.1046/j.1445-5994.2001.00039.x.

    Article  CAS  PubMed  Google Scholar 

  10. Parsi MA, Achkar JP, Richardson S, et al. Predictors of response to infliximab in patients with Crohn’s disease. Gastroenterology. 2002;123:707–713. doi:10.1053/gast.2002.35390.

    Article  CAS  PubMed  Google Scholar 

  11. Rudolph SJ, Weinberg DI, McCabe RP. Long-term Durability of Crohn’s disease treatment with infliximab. Dig Dis Sci. 2007;53:1033–1041. doi:10.1007/s10620-007-9969-z.

    Article  PubMed  CAS  Google Scholar 

  12. Vermeire S, Louis E, Carbonez A, et al. Demographic and clinical parameters influencing the short-term outcome of anti-tumor necrosis factor (infliximab) treatment in Crohn’s disease. Am J Gastroenterol. 2002;97:2357–2363. doi:10.1111/j.1572-0241.2002.05991.x.

    Article  CAS  PubMed  Google Scholar 

  13. Vermeire S, Noman M, Van Assche G, Baert F, D’Haens G, Rutgeerts P. Effectiveness of concomitant immunosuppressive therapy in suppressing the formation of antibodies to infliximab in Crohn’s disease. Gut. 2007;56:1226–1231. doi:10.1136/gut.2006.099978.

    Article  CAS  PubMed  Google Scholar 

  14. Baert F, Noman M, Vermeire S, et al. Influence of immunogenicity on the long-term efficacy of infliximab in Crohn’s disease. N Engl J Med. 2003;348:601–608. doi:10.1056/NEJMoa020888.

    Article  CAS  PubMed  Google Scholar 

  15. Fefferman DS, Lodhavia PJ, Alsahli M, et al. Smoking and immunomodulators do not influence the response or duration of response to infliximab in Crohn’s disease. Inflamm Bowel Dis. 2004;10:346–351. doi:10.1097/00054725-200407000-00004.

    Article  PubMed  Google Scholar 

  16. Kinney T, Rawlins M, Kozarek R, France R, Patterson D. Immunomodulators and “on demand” therapy with infliximab in Crohn’s disease: clinical experience with 400 infusions. Am J Gastroenterol. 2003;98:608–612.

    CAS  PubMed  Google Scholar 

  17. Luna-Chadid M, Perez Calle JL, Mendoza JL, et al. Predictors of response to infliximab in patients with fistulizing Crohn’s disease. Rev Esp Enferm Dig. 2004;96:379–381.

    Article  CAS  PubMed  Google Scholar 

  18. Lichtenstein GR, Wagner C, Olson A, Hegedus R, Bala M, Sandborn WJ. Infliximab administered as 3-dose induction followed by scheduled maintenance therapy in IBD: comparable clinical outcomes with or without concomitant immunomodulators. Gastroenterology. 2007;132:A146.

    Google Scholar 

  19. 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;134:1861–1868. doi:10.1053/j.gastro.2008.03.004.

    Article  PubMed  CAS  Google Scholar 

  20. Seddik M, Meliez H, Seguy D, Viget N, Cortot A, Colombel JF. Pneumocystis jiroveci (carinii) pneumonia following initiation of infliximab and azathioprine therapy in a patient with Crohn’s disease. Inflamm Bowel Dis. 2004;10:436–437. doi:10.1097/00054725-200407000-00017.

    Article  PubMed  Google Scholar 

  21. Toruner M, Loftus EV Jr, Harmsen WS, et al. Risk factors for opportunistic infections in patients with inflammatory bowel disease. Gastroenterology. 2008;134:929–936. doi:10.1053/j.gastro.2008.01.012.

    Article  PubMed  Google Scholar 

  22. 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;44:265–267. doi:10.1097/MPG.0b013e31802f6424.

    Article  PubMed  Google Scholar 

  23. Rosh JR, Gross T, Mamula P, Griffiths A, Hyams J. Hepatosplenic T-cell lymphoma in adolescents and young adults with Crohn’s disease: a cautionary tale? Inflamm Bowel Dis. 2007;13:1024–1030. doi:10.1002/ibd.20169.

    Article  PubMed  Google Scholar 

  24. Faubion WA Jr, Loftus EV Jr, Harmsen WS, Zinsmeister AR, Sandborn WJ. The natural history of corticosteroid therapy for inflammatory bowel disease: a population-based study. Gastroenterology. 2001;121:255–260. doi:10.1053/gast.2001.26279.

    Article  CAS  PubMed  Google Scholar 

  25. Gasche C, Scholmerich J, Brynskov J, et al. A simple classification of Crohn’s disease: report of the working party for the world congresses of gastroenterology, Vienna 1998. Inflamm Bowel Dis. 2000;6:8–15.

    CAS  PubMed  Google Scholar 

  26. Dupont W, Plummer W. PS power and sample size program available for free on the internet. Control Clin Trials. 1997;18:274. doi:10.1016/S0197-2456(97)00074-3.

    Article  Google Scholar 

  27. Soper D. The free statistics calculator website. Online Software http://www.danielsoper.com/statcalc/; 2008.

  28. Moss AC, Fernandez-Becker N, Jo KK, et al. The impact of infliximab infusion reactions on long-term outcomes in patients with Crohn’s disease. Aliment Pharmacol Ther. 2008;28(2):221–227.

    Article  CAS  PubMed  Google Scholar 

  29. Keshavarzian A, Mayer L, Salzberg B, et al. A multicenter retrospective experience of infliximab in Crohn’s disease patients: infusion reaction rates and treatment persistency. Gastroenterol Hepatol. 2007;3:381–390.

    Google Scholar 

  30. Rutgeerts P, D’Haens G, Targan S, et al. Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn’s disease. Gastroenterology. 1999;117:761–769. doi:10.1016/S0016-5085(99)70332-X.

    Article  CAS  PubMed  Google Scholar 

  31. Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet. 2002;359:1541–1549. doi:10.1016/S0140-6736(02)08512-4.

    Article  CAS  PubMed  Google Scholar 

  32. Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med. 2004;350:876–885. doi:10.1056/NEJMoa030815.

    Article  CAS  PubMed  Google Scholar 

  33. Lemann M, Mary JY, Duclos B, et al. Infliximab plus azathioprine for steroid-dependent Crohn’s disease patients: a randomized placebo-controlled trial. Gastroenterology. 2006;130:1054–1061. doi:10.1053/j.gastro.2006.02.014.

    Article  CAS  PubMed  Google Scholar 

  34. van den Brande JM, Peppelenbosch MP, Hommes DW. Steroid-independent Crohn’s disease patients also benefit from combination therapy of infliximab plus azathioprine. Gastroenterology. 2006;131:1362–1363. doi:10.1053/j.gastro.2006.08.054.

    Article  PubMed  Google Scholar 

  35. 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;4:1248–1254. doi:10.1016/j.cgh.2006.06.025.

    Article  CAS  PubMed  Google Scholar 

  36. Sandborn WJ, Rutgeerts P, Reinisch W, et al. SONIC; a randomized, double-blind, controlled trial comparing inlfiximab and infliximab plus azathioprine to azathioprine in patients with Crohn’s disease Naive to immunomodulators and biologic therapy. Am J Gastroenterol. 2008;103(S1):S436.

    Google Scholar 

  37. Orlando A, Colombo E, Kohn A, et al. Infliximab in the treatment of Crohn’s disease: predictors of response in an Italian multicentric open study. Dig Liver Dis. 2005;37:577–583. doi:10.1016/j.dld.2005.01.019.

    Article  CAS  PubMed  Google Scholar 

  38. Lionetti P, Bronzini F, Salvestrini C, et al. Response to infliximab is related to disease duration in paediatric Crohn’s disease. Aliment Pharmacol Ther. 2003;18:425–431. doi:10.1046/j.1365-2036.2003.01672.x.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

Our patients, the pheresis unit staff, and our gastroenterology colleagues at BIDMC.

Competing Interests

A.C. Moss has received honoraria from Schering-Plough, consulted for Abbott, and is on the speakers’ bureau for UCB and Elan. A.S. Cheifetz is on the speakers’ bureau for Centocor and Abbott, and has consulted for Centocor, Abbott, and UCB.

Funding

N.F.-B. is supported by an NIH T32 grant.

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Correspondence to Adam S. Cheifetz.

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A.C. Moss and K. Jo Kim contributed equally to this work.

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Moss, A.C., Kim, K.J., Fernandez-Becker, N. et al. Impact of Concomitant Immunomodulator Use on Long-Term Outcomes in Patients Receiving Scheduled Maintenance Infliximab. Dig Dis Sci 55, 1413–1420 (2010). https://doi.org/10.1007/s10620-009-0856-7

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  • DOI: https://doi.org/10.1007/s10620-009-0856-7

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