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Therapeutic Drug Monitoring of Anti-TNF Therapy in Inflammatory Bowel Disease

  • Inflammatory Bowel Disease (G Lichtenstein, Section Editor)
  • Published:
Current Treatment Options in Gastroenterology Aims and scope Submit manuscript

Opinion statement

While anti-TNF agents have had a marked impact in the treatment of inflammatory bowel disease, a significant number of patients lose their response to these medications over time. Clinical trials have demonstrated that antibodies against anti-TNF medications may impact treatment response and increase the risk of infusion reaction. Scheduled dosing and concurrent use of immunomodulators may help to mitigate these risks via inhibiting the formation of these antibodies. The recent availability of assays to measure anti-TNF drug levels and antibodies against anti-TNFs offer the opportunity to assess patients who have lost response with infliximab and adalimumab, and potentially determine the most appropriate therapeutic strategy. There is growing evidence that such testing improves patient outcomes and is cost-effective, although heterogeneity in the assays used in clinical and observational trials has resulted in mixed results.

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References and Recommended Reading

  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):1383–95.

    Article  CAS  PubMed  Google Scholar 

  2. 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(4):1054–61.

    Article  CAS  PubMed  Google Scholar 

  3. D’Haens G, Baert F, van Assche G, 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 

  4. Sandborn WJ, Hanauer SB, Rutgeerts P, et al. Adalimumab for maintenance treatment of Crohn’s disease: results of the CLASSIC II trial. Gut. 2007;56(9):1232–9.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  6. Schreiber S, Khaliq-Kareemi M, Lawrance IC, et al. Maintenance therapy with certolizumab pegol for Crohn’s disease. N Engl J Med. 2007;357(3):239–50.

    Article  CAS  PubMed  Google Scholar 

  7. Cassinotti A, Travis S. Incidence and clinical significance of immunogenicity to infliximab in Crohn’s disease: a critical systematic review. Inflamm Bowel Dis. 2009;15(8):1264–75.

    Article  PubMed  Google Scholar 

  8. Lichtenstein GR. Comprehensive review: antitumor necrosis factor agents in inflammatory bowel disease and factors implicated in treatment response. Ther Adv Gastroenterol. 2013;6(4):269–93.

    Article  Google Scholar 

  9. Imaeda H, Takahashi K, Fujimoto T, et al. Clinical utility of newly developed immunoassays for serum concentrations of adalimumab and anti-adalimumab antibodies in patients with Crohn’s disease. J Gastroenterol. Apr 11 2013.

  10. Hanauer SB, Sandborn WJ, Rutgeerts P, et al. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn’s disease: the CLASSIC-I trial. Gastroenterology. 2006;130(2):323–33. quiz 591.

    Article  CAS  PubMed  Google Scholar 

  11. Sandborn WJ, Feagan BG, Stoinov S, et al. Certolizumab pegol for the treatment of Crohn’s disease. N Engl J Med. 2007;357(3):228–38.

    Article  CAS  PubMed  Google Scholar 

  12. Ben-Horin S, Yavzori M, Katz L, et al. The immunogenic part of infliximab is the F(ab’)2, but measuring antibodies to the intact infliximab molecule is more clinically useful. Gut. 2011;60(1):41–8.

    Article  CAS  PubMed  Google Scholar 

  13. Ordas I, Mould DR, Feagan BG, Sandborn WJ. Anti-TNF monoclonal antibodies in inflammatory bowel disease: pharmacokinetics-based dosing paradigms. Clin Pharmacol Ther. 2012;91(4):635–46.

    Article  CAS  PubMed  Google Scholar 

  14. 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):962–71.

    Article  PubMed  Google Scholar 

  15. 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.

    Article  CAS  PubMed  Google Scholar 

  16. Khanna R, Sattin BD, Afif W, et al. Review article: a clinician’s guide for therapeutic drug monitoring of infliximab in inflammatory bowel disease. Aliment Pharmacol Ther. 2013;38(5):447–59.

    Article  CAS  PubMed  Google Scholar 

  17. 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):944–8.

    Article  CAS  PubMed  Google Scholar 

  18. Wang SL, Ohrmund L, Hauenstein S, et al. Development and validation of a homogeneous mobility shift assay for the measurement of infliximab and antibodies-to-infliximab levels in patient serum. J Immunol Methods. 2012;382(1–2):177–88.

    Article  CAS  PubMed  Google Scholar 

  19. Infliximab Concentration and Anti-Infliximab Antibody. LabHorizons: a Newsletter for Clients. 11/2012 2012;13(11–12):3.

  20. 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(7):601–8.

    Article  CAS  PubMed  Google Scholar 

  21. 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):917–24.

    Article  CAS  PubMed  Google Scholar 

  22. 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(9):1226–31.

    Article  CAS  PubMed  Google Scholar 

  23. Hanauer SB, Wagner CL, Bala M, et al. Incidence and importance of antibody responses to infliximab after maintenance or episodic treatment in Crohn’s disease. Clin Gastroenterol Hepatol: Off Clin Pract J Am Gastroenterol Assoc. 2004;2(7):542–53.

    Article  CAS  Google Scholar 

  24. 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: Off Clin Pract J Am Gastroenterol Assoc. 2006;4(10):1248–54.

    Article  CAS  Google Scholar 

  25. Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353(23):2462–76.

    Article  CAS  PubMed  Google Scholar 

  26. 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):1861–8.

    Article  PubMed  Google Scholar 

  27. Sandborn WJ, van Assche G, Reinisch W, et al. Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2012;142(2):257–65. e251-253.

    Article  CAS  PubMed  Google Scholar 

  28. 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):1628–40.

    Article  CAS  PubMed  Google Scholar 

  29. 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):688–95. e682.

    Article  CAS  PubMed  Google Scholar 

  30. Keizer RJ, Huitema AD, Schellens JH, Beijnen JH. Clinical pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet. 2010;49(8):493–507.

    Article  CAS  PubMed  Google Scholar 

  31. Reinisch W, Feagan BG, Rutgeerts PJ, et al. Infliximab Concentration and Clinical Outcome in Patients With Ulcerative Colitis. Gastroenterology. 2012;142(5):S114 [Abstract].

    Google Scholar 

  32. Li J, Paulson SK, Chiu Y-L, Robinson A, Lomax KG, Pollac PF. Evaluation of potential correlations between serum adalimumab concentration and remission in patients with Crohn’s disease in classic I and II. Gastroenterology. 2010;138(5):S101 [Abstract].

    Google Scholar 

  33. Sandborn WJ, Schreiber S, Hanauer SB, Colombel JF, Bloomfield R, Lichtenstein GR. Reinduction with certolizumab pegol in patients with relapsed Crohn’s disease: results from the PRECiSE 4 Study. Clin Gastroenterol Hepatol: Off Clin Pract J Am Gastroenterol Assoc. 2010;8(8):696–702. e691.

    Article  CAS  Google Scholar 

  34. Sandborn WJ, Hanauer SB, Pierre-Louis B, Lichtenstein GR. Certolizumab pegol plasma concentration and clinical remission in Crohn’s disease. Gastroenterology. 2012;142(5):S563 [Abstract Su2079].

    Google Scholar 

  35. Colombel JF, Feagan BG, Sandborn WJ, Van Assche G, Robinson AM. Therapeutic drug monitoring of biologics for inflammatory bowel disease. Inflamm Bowel Dis. 2012;18(2):349–58.

    Article  PubMed  Google Scholar 

  36. Afif W, Loftus E Jr, Faubion W, Kane S, Bruining D, Hanson K, et al. Clinical utility of measuring infliximab and human anti-chimeric antibody concentrations in patients with inflammatory bowel disease. Am J Gastroenterol. 2010;105:1133–1139.

    Google Scholar 

  37. Pariente B, Pineton de Chambrun G, Krzysiek R, et al. Trough levels and antibodies to infliximab may not predict response to intensification of infliximab therapy in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2012;18(7):1199–206.

    Article  PubMed  Google Scholar 

  38. Vande Casteele N, Compernolle G, Ballet V, et al. Results on the optimisation phase of the prospective controlled trough level adapted infliximab treatment (TAXIT) trial. Gastroenterology. 2012;142(5):S211–2.

    Google Scholar 

  39. Vande Casteele N, Gils A, Ballet V, et al. Randomised controlled trial of drug level verus clinically based dosing of infliximan maintenance therapy in IBD: final results of the TAXIT study. U Eur Gastroenterol J. 2013;1:A1.

    Article  Google Scholar 

  40. 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. Jul 22 2013.

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Conflict of Interest

Frank I. Scott declares that he has no conflict of interest.

Gary R. Lichtenstein has received consultancy payments from Abbott Corporation/Abbvie, Alaven, Bristol-Myers Squibb, Elan, Ferring, Hospira, Janssen Orthobiotech, Millenium Pharmaceuticals, Ono Pharmaceuticals, Pfizer Pharmaceuticals, Prometheus Laboratories, Inc., Salix Pharmaceuticals, Santarus, Shire Pharmaceuticals, Takeda, UCB, and Warner; honoraria from Ironwood and Luitpold / American Regent; and a research grant from Warner Chilcotte.

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.

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Authors and Affiliations

  1. Division of Gastroenterology, Department of Medicine, University of Pennsylvania, 9 Penn Tower, 1 Civic Center Boulevard, Philadelphia, PA, 19104, USA

    Frank I. Scott MD, MSCE

  2. IBD Program, Hospital of the University of Pennsylvania, Division of Gastroenterology, Department of Medicine, University of Pennsylvania, 9 Penn Tower, 1 Civic Center Boulevard, Philadelphia, PA, 19104, USA

    Gary R. Lichtenstein MD

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Correspondence to Frank I. Scott MD, MSCE.

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Scott, F.I., Lichtenstein, G.R. Therapeutic Drug Monitoring of Anti-TNF Therapy in Inflammatory Bowel Disease. Curr Treat Options Gastro 12, 59–75 (2014). https://doi.org/10.1007/s11938-013-0004-5

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