Skip to main content

Advertisement

SpringerLink
Log in

Pharmacology and metabolism of infliximab biosimilars — A new treatment option in inflammatory bowel diseases

  • Review Article
  • Published:
Pharmacological Reports Aims and scope Submit manuscript

Abstract

Biological therapy with monoclonal antibodies to tumor necrosis factor alpha (TNF-α) was shown in large clinical trials to be effective in inducing and maintaining clinical remission in patients with moderate to severe Crohn’s disease (CD) and ulcerative colitis (UC). Infliximab, the first anti-TNF-α biologic drug, has significantly improved inflammatory bowel disease (IBD) treatment outcomes by preventing structural damage progression, thereby reducing complications and the need for surgery and hospitalization. The major concern associated with the use of biologics is their high cost. However, as these therapies lose patent protection, cheaper biosimilar versions of the originator products are being developed, such as the infliximab biosimilar CT-P13. Position statements from several scientific societies and some experts in their reviews have expressed concerns to the concept of extrapolation without direct IBD clinical evidence, whereas European Medicines Agency (EMA) experts have supported extrapolation.

In this review, we focus on the pharmacokinetics, pharmacodynamics properties and comparative effectiveness of anti-TNF-α biosimilars, related to their use in IBD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Dig Nat 2007;448(7152):427–34.

    Article  CAS  Google Scholar 

  2. Frolkis A, Dieleman LA, Bakema H, Panaccione R, Ghosh S, Fedorak RN, et al. Environment and the inflammatory bowel disease. Can J Gastroenterol 2013;27(3):e18–24.

    Article  Google Scholar 

  3. Shanahan F, Bernstein CN. The evolving epidemiology of inflammatory bowel disease. Curr Opin Gastroenterol 2009;25(4):301–5.

    Article  Google Scholar 

  4. 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;359:1541–9.

    Article  CAS  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;362:1383–95.

    Article  CAS  Google Scholar 

  6. Targan SR, Hanauer SB, van Deventer SJH, 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. N Engl J Med 1997;337:1029–35.

    Article  CAS  Google Scholar 

  7. Sands BE, Anderson FH, Bernstein CN, Chey WY, Feagan BG, Fedorak RN, et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med 2004;350:876–85.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  9. Wang J, Chow SC. On the regulatory approval pathway of biosimilar products. Pharmaceuticals 2012;5:353–68.

    Article  Google Scholar 

  10. Kim J, An Hong J, Kudrin A. P137 5 year budget impact analysis of CT-P13 (infliximab) for the treatment of Crohn’s disease in UK, Italy and France. J Crohns Colitis 2015;9:S144–5.

    Google Scholar 

  11. Jha A, Dunlop W, Upton A. Budget impact analysis of introducing biosimilar infliximab for the treatment of gastro intestinal disorders in five European countries. J Crohns Colitis 2015;9:S427.

    Google Scholar 

  12. Kay J, Smolen JS. Biosimilars to treat inflammatory arthritis: the challenge of proving identity. Ann Rheum Dis 2013;72:1589–93.

    Article  CAS  Google Scholar 

  13. Beck A, Reichert JM. Approval of the first biosimilar antibodies in Europe: a major landmark for the biopharmaceutical industry. MAbs 2013;5:621–3.

    Article  Google Scholar 

  14. Rinaudo-Gaujous M, Paul S, Tedesco ED, Genin C, Roblin X, Peyrin-Biroulet L. Review article: biosimilars are the next generation of drugs for liver and gastrointestinal diseases. Aliment Pharmacol Ther 2013;38:914–24.

    Article  CAS  Google Scholar 

  15. Hlavaty T, Letkovsky J. Biosimilars in the therapy of inflammatory bowel diseases. Eur J Gastroenterol Hepatol 2014;26:581–7.

    Article  CAS  Google Scholar 

  16. Genazzani A, Altomare G, Balato N, Cusano F, De Pita O, Loconsole F, et al. Biosimilar infliximab: an expert view. G Ital Dermatol Venereol 2015;150: 449–59.

    CAS  PubMed  Google Scholar 

  17. McClellan JE, Udata C, Yin D, Salts S, Johnson TR, Derzi M, et al. Comparative structural, functional, nonclinical, and phase 1 similarity assessments of PF-06438179, a potential biosimilar to infliximab, and marketed reference products. J Crohns Colitis 2015;9:S94–5.

    Google Scholar 

  18. Lee JF, Litten JB, Grampp G. Comparabillity and biosimilarity considerations for the healthcare provider. Curr Med Res Opin 2012;28:1053–8.

    Article  CAS  Google Scholar 

  19. Gomollón F. Biosimilars in inflammatory bowel disease: ready for prime time? Curr Opin Gastroenterol 2015;31(4):290–5.

    Article  Google Scholar 

  20. Crommelin D, Storm G, Verrijk R, De Leede L, Jiskoot W, Hennink W. Shifting paradigms: biopharmaceuticals versus low molecular weight drugs. Int J Pharm 2003;266:3–16.

    Article  CAS  Google Scholar 

  21. Schneider CK. Biosimilars in rheumatology: the wind of change. Ann Rheum Dis 2013;72:315–8.

    Article  CAS  Google Scholar 

  22. Feagan BG, Choquette D, Ghosh S, Gladman DD, Ho V, Meibohm B, et al. The challenge of indication extrapolation for infliximab biosimilars. Biologicals 2014;42:177–83.

    Article  CAS  Google Scholar 

  23. Fiorino G, Girolomoni G, Lapadula G, Orlando A, Danese S, Olivieri I, et al. The use of biosimilars in immune-mediated disease: a joint Italian Society of Rheumatology (SIR), Italian Society of Dermatology (SIDeMaST), and Italian Group of Inflammatory Bowel Disease (IG-IBD) position paper. Autoimmun Rev 2014;13:751–5.

    Article  Google Scholar 

  24. Devlin SM, Bressler B, Bernstein CN, Fedorak RN, Bitton A, Singh H, et al. Overview of subsequent entry biologics for the management of inflammatory bowel disease and Canadian Association of Gastroenterology position statement on subsequent entry biologics. Can J Gastroenterol 2013;27:567–71.

    Article  Google Scholar 

  25. Arguelles-Arias F, Barreiro-de-Acosta M, Carballo F, Hinojosa J, Tejerina T. Joint position statement by Sociedad Espanola de Patologia Digestiva (Spanish Society of Gastroenterology) and Sociedad Espanola de Farmacologia (Spanish Society of Pharmacology) on biosimilar therapy for inflammatory bowel disease. Rev Esp Enferm Dig 2013;105:37–43.

    Article  Google Scholar 

  26. Annese V, Vecchi M, Italian Group for the Study of IBD (IG-IBD). Use of biosimilars in inflammatory bowel disease: statements of the Italian Group for Inflammatory Bowel Disease. Dig Liver Dis 2014;46:963–8.

    Article  Google Scholar 

  27. Danese S, Gomollon F, Governing Board and Operational Board of ECCO. ECCO position statement: the use of biosimilar medicines in the treatment of inflammatory bowel disease (IBD). J Crohns Colitis 2013;7:586–9.

    Article  Google Scholar 

  28. Vermeire S, Louis E, Dewit O, Franchimont D, Moreels T, Ferrante M, et al. Clinical and scientific aspects related to biosimilars in inflammatory bowel diseases Group (BIRD) (IBD): position document of the Belgian IBD Research & Development. Acta Gastroenterol Belg 2015;78:26–9.

    CAS  PubMed  Google Scholar 

  29. European Medicines Agency. Questions and answers on biosimilar medicines (similar biological medicinal products); 2012, http://www.ema.europa.eu/docs/en_GB/document_library/Medicine_QA/2009/12/WC500020062.pdf/.

  30. Baji P, Péntek M, Czirják L, Szekanecz Z, Nagy G, Gulácsi L, et al. Efficacy and safety of infliximab biosimilar compared to other biological drugs in rheumatoid arthritis: a mixed treatment comparison. Eur J Health Econ 2014;15:S53–64.

    Article  Google Scholar 

  31. Baji P, Péntek M, Szántó S, Gáher P, Gulácsi L, Balogh O, et al. Comparative efficacy and safety of biosimilar infliximab and other biological treatments in ankylosing spondylitis: systematic literature review and meta-analysis. Eur J Health Econ 2014;15:S45–52.

    Article  Google Scholar 

  32. Yoo DH, Hrycaj P, Miranda P, Ramiterre E, Piotrowski M, Shevchuk S, et al. A randomised, double-blind, parallel group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study. Ann Rheum Dis 2013;72:1613–20.

    Article  CAS  Google Scholar 

  33. Park W, Hrycaj P, Jeka S, Kovalenko V, Lysenko G, Miranda P, et al. A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS. Arthritis Res Ther 2016;18(January (1)):25.

    Article  Google Scholar 

  34. Jung YS, Park DI, Kim YH, Lee JH, Seo PJ, Cheon JH, et al. Efficacy and safety of CT-P13, a biosimilar of infliximab, in patients with inflammatory bowel disease: a retrospective multicenter study. J Gastroenterol Hepatol 2015;30(12):1705–12. http://dx.doi.org/10.1111/jgh.12997.

    Article  CAS  Google Scholar 

  35. Gecse K, Farkas K, Lovasz BD, Banai J, Golovics PA, Kristof T, et al. Biosimilar infliximab in inflammatory bowel diseases: first interim results from a prospective nationwide observational cohort. Gastroenterology 2015;148. S–865–6.

    Article  Google Scholar 

  36. Murphy C, Sugrue K, Mohamad G, McCarthy J, Buckley M. Biosimilar but not the same. J Crohns Colitis 2015;9:S331–2.

    Google Scholar 

  37. Park W, Lee SJ, Yun J, Yoo DH. Comparison of the pharmacokinetics and safety of three formulations of infliximab (CT-P13, EU-approved reference infliximab and the US-licensed reference infliximab) in healthy subjects: a randomized, double-blind, three-arm, parallel group, single-dose, phase I study. Expert Rev Clin Immunol 2015;11(Suppl. 1):S25–31.

    Article  Google Scholar 

  38. Danese S, Fiorino G, Michetti P. Viewpoint: knowledge and view points on biosimilar monoclonal antibodies among members of the European Crohn’s and Colitis Organization. J Crohns Colitis 2014;8(11):1548–50.

    Article  Google Scholar 

  39. Crohn’s Colitis Foundation of America (CCFA) Crohn’s and Colitis Foundation of America position statement: biosimilars; 2015 [accessed 18.12.15].

  40. Ben-Horin S, Yavzori M, Benhar I, Fudim E, Picard O, Ungar B, et al. Cross-immunogenicity: antibodies to infliximab in Remicade-treated patients with IBD similarly recognise the biosimilar Remsima. Gut 2015. http://dx.doi.org/10.1136/gutjnl-2015-309290.

  41. Gils A, Storme R, Dreesen E, van Stappen T, Declerck PJ. The biosimilars of infliximab are equally well quantified in a clinically validated infliximab assay. J Crohns Colitis 2015;9:S97.

    Google Scholar 

  42. Weise M, Bielsky M, De Smet K, Ehmann F, Ekman N, Giezen T, et al. Biosimilars: what clinicians should know. Blood 2012;120:5111–7.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Medical University of Lodz, Łódź, Poland

    Marcin Włodarczyk & Aleksandra Sobolewska-Włodarczyk

  2. Department of Biochemistry, Medical University of Lodz, Łódź, Poland

    Marcin Włodarczyk, Jakub Fichna & Aleksandra Sobolewska-Włodarczyk

  3. Department of General and Colorectal Surgery, Medical University of Lodz, Łódź, Poland

    Marcin Włodarczyk

Authors
  1. Marcin Włodarczyk
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jakub Fichna
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aleksandra Sobolewska-Włodarczyk
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marcin Włodarczyk.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Włodarczyk, M., Fichna, J. & Sobolewska-Włodarczyk, A. Pharmacology and metabolism of infliximab biosimilars — A new treatment option in inflammatory bowel diseases. Pharmacol. Rep 68, 797–801 (2016). https://doi.org/10.1016/j.pharep.2016.04.006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1016/j.pharep.2016.04.006

Keywords

Search

Navigation