Skip to main content

Advertisement

SpringerLink
Log in

Does Similarity Breed Contempt? A Review of the Use of Biosimilars in Inflammatory Bowel Disease

  • Invited Review
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

The introduction of therapeutic monoclonal antibodies directed against tumor necrosis factor-α has revolutionized the treatment of inflammatory bowel disease (IBD) by improving quality of life, decreasing the frequency and length of hospital admissions, and reducing corticosteroid use. Nevertheless, biologics are very expensive, substantially contributing to the cost of care for patients with IBD. To reduce this cost and improve treatment access, biosimilars, which are therapeutic monoclonal antibodies (biologicals) similar to but not identical to the reference biologic, were introduced. Despite their potential benefits, the adoption and uptake of biosimilars have varied considerably across the USA and Europe. Here, we highlight the current biosimilar therapeutic landscape, discuss barriers to their use, and provide an overview of published studies evaluating the efficacy and safety of biosimilars 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

Fig. 1

Similar content being viewed by others

References

  1. GBD 2017 Inflammatory Bowel Disease Collaborators. The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol. 2020;5:17–30.

  2. Cholapranee A, Hazlewood GS, Kaplan GG et al. Systematic review with meta-analysis: comparative efficacy of biologics for induction and maintenance of mucosal healing in Crohn’s disease and ulcerative colitis controlled trials. Aliment Pharmacol Ther. 2017;45:1291–1302.

    Article  CAS  Google Scholar 

  3. Van Assche G, Vermeire S, Rutgeerts P. The potential for disease modification in Crohn’s disease. Nat Rev Gastroenterol Hepatol. 2010;7:79–85.

    Article  Google Scholar 

  4. Targownik LE, Kaplan GG, Witt J et al. Longitudinal trends in the direct costs and health care utilization ascribable to inflammatory bowel disease in the biologic era: results from a Canadian population-based analysis. Am J Gastroenterol. 2020;115:128–137.

    Article  Google Scholar 

  5. Park KT, Ehrlich OG, Allen JI. The cost of inflammatory bowel disease: an initiative from the Crohn’s & Colitis Foundation. Inflamm Bowel Dis. 2020;26:1–10.

    Article  CAS  Google Scholar 

  6. Bassi A, Dodd S, Williamson K, Bodger K. Cost of illness of inflammatory bowel disease in the UK: a single centre retrospective study. Gut. 2004;53:1471–1478.

    Article  CAS  Google Scholar 

  7. Lakatos P. European experience of infliximab biosimilars for the treatment of inflammatory bowel disease. Gastroenterol Hepatol (N Y). 2016;12:119–121.

    Google Scholar 

  8. European Medicines Agency and the European Commission. Biosimilars in the EU: information guide for healthcare providers. Available at: https://www.ema.europa.eu/en/documents/leaflet/biosimilars-eu-information-guide-healthcare-professionals_en.pdf. Accessed December 28, 2020.

  9. Food and Drug Administration. Biosimilars. Available at: https://www.fda.gov/drugs/therapeutic-biologics-applications-bla/biosimilars. Accessed December 28, 2020.

  10. Joachim R. Weighing the potential of Humira biosimilars in the U.S. – competitive dynamics analysis. Biosimilar Development. 2020. Available at: https://www.biosimilardevelopment.com/doc/weighing-the-potential-of-humira-biosimilars-in-the-u-s-competitive-dynamics-analysis-0001. Accessed January 5, 2021.

  11. Goll GL, Kvien TK. An opportunity missed: biosimilars in the United States. Arthritis Rheumatol. 2020;72:1046–1048.

    Article  Google Scholar 

  12. Moorkens E, Vulto AG, Huys I et al. Policies for biosimilar uptake in Europe: an overview. PLoS One 2017;12:e0190147.

    Article  Google Scholar 

  13. Gulacsi L, Pentek M, Rencz F et al. Biosimilars for the management of inflammatory bowel diseases: economic considerations. Curr Med Chem. 2019;26:259–269.

    Article  CAS  Google Scholar 

  14. Hakim A, Ross JS. Obstacles to the adoption of biosimilars for chronic diseases. JAMA. 2017;317:2163–2164.

    Article  Google Scholar 

  15. Pfizer Inc. vs. Johnson & Johnson. Civil action no. 17-cv-4180. Available at: https://www.leagle.com/decision/infdco20180813a93. Accessed January 5, 2021.

  16. Yazdany J, Adams Dudley R, Lin GA et al. Out-of-pocket costs for infliximab and its biosimilar for rheumatoid arthritis under Medicare part D. JAMA 2018;320:931–933.

    Article  Google Scholar 

  17. Kurki P, van Aerts L, Wolff-Holz E et al. Interchangeability of biosimilars: a European perspective. BioDrugs. 2017;31:83–91.

    Article  CAS  Google Scholar 

  18. Dutcher SK, Fazio-Eynullayeva E, Eworuke E et al. Understanding utilization patterns of biologics and biosimilars in the United States to support postmarketing studies of safety and effectiveness. Pharmacoepidemiol Drug Saf. 2020;29:786–795.

    Article  CAS  Google Scholar 

  19. Andersen JT, Jensen TB. Variation in biosimilar uptake in Europe. JAMA Intern Med. 2021;181:403–404. https://doi.org/10.1001/jamainternmed.2020.6567.

  20. Leonard E, Wascovich M, Oskouei S et al. Factors affecting health care provider knowledge and acceptance of biosimilar medicines: a systematic review. J Manag Care Spec Pharm. 2019;25:102–112.

    PubMed  Google Scholar 

  21. Danese S, Fiorino G, Michetti P. Viewpoint: knowledge and viewpoints on biosimilar monoclonal antibodies among members of the European Crohn’s and Colitis Organization. J Crohns Colitis. 2014;8:1548–1550.

    Article  Google Scholar 

  22. Danese S, Fiorino G, Michetti P. Changes in biosimilar knowledge among European Crohn’s Colitis Organization [ECCO] members: an updated survey. J Crohns Colitis. 2016;10:1362–1365.

    Article  Google Scholar 

  23. Peyrin-Biroulet L, Lonnfors S, Avedano L et al. Changes in inflammatory bowel disease patients’ perspectives on biosimilars: a follow-up survey. United Europ Gastroenterol J. 2019;7:1345–1352.

    Article  Google Scholar 

  24. Teeple A, Ginsburg S, Howard L et al. Patient attitudes about non-medical switching to biosimilars: results from an online patient survey in the United States. Curr Med Res Opin. 2019;35:603–609.

    Article  CAS  Google Scholar 

  25. Colloca L, Panaccione R, Murphy TK. The clinical implications of nocebo effects for biosimilar therapy. Front Pharamcol. 2019.

  26. Pouillon L, Socha M, Demore B et al. The nocebo effect: a clinical challenge in the era of biosimilars. Expert Rev Clin Immunol. 2018;14:739–749.

    Article  CAS  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;7:586–589.

    Article  Google Scholar 

  28. Danese S, Fiorino G, Raine T et al. ECCO position statement on the use of biosimilars for inflammatory bowel disease—an update. J Crohns Colitis. 2017;11:26–34.

    Article  Google Scholar 

  29. de Ridder L, Assa A, Bronsky J et al. Use of biosimilars in pediatric inflammatory bowel disease: an updated position statement of pediatric IBD porto group of ESPGHAN. J Pediatr Gastroenterol Nutr. 2019;68:144–153.

    Article  Google Scholar 

  30. Crohn’s & Colitis Foundation. Biosimilars: position statement. Updated Nov 24, 2020. Available at: https://www.crohnscolitisfoundation.org/sites/default/files/2019-06/biosimilars-statement-needs_0.pdf. Accessed January 5, 2021.

  31. Park W, Hrycaj P, Jeka S et al. A randomized, double-blind, multicenter, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study. Ann Rheum Dis. 2013;72:1605–1612.

    Article  CAS  Google Scholar 

  32. Yoo DH, Racewicz A, Brzezicki J et al. A phase III randomized study to evaluate the efficacy and safety of CT-P13 compared with reference infliximab in patients with active rheumatoid arthritis: 54-week results from the PLANETRA study. Arthritis Res Ther. 2016;18:82.

    Article  Google Scholar 

  33. Weinblatt ME, Baranauskaite A, Niebrzydowski J et al. Phase III randomized study of sb5, an adalimumab biosimilar, versus reference adalimumab in patients with moderate-to-severe rheumatoid arthritis. Arthritis Rheumatol. 2018;70:40–48.

    Article  CAS  Google Scholar 

  34. Weinblatt ME, Baranauskaite A, Dokoupilova E et al. Switching from reference adalimumab to sb5 (adalimumab biosimilar) in patients with rheumatoid arthritis: fifty-two-week phase III randomized study results. Arthritis Rheumatol. 2018;70:832–840.

    Article  CAS  Google Scholar 

  35. Jorgensen KK, Olsen IC, Goll GL et al. Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomised, double-blind, non-inferiority trial. Lancet. 2017;389:2304–2316.

    Article  Google Scholar 

  36. Goll GL, Jorgensen KK, Sexton J et al. Long-term efficacy and safety of biosimilar infliximab (CT-P13) after switching from originator infliximab: open-label extension of the NOR-SWITCH trial. J Intern Med. 2019;285:653–669.

    Article  CAS  Google Scholar 

  37. Ye BD, Pesegova M, Alexeeva O et al. Efficacy and safety of biosimilar CT-P13 compared with originator infliximab in patients with active Crohn’s disease: an international, randomised, double-blind, phase 3 non-inferiority study. Lancet. 2019;393:1699–1707.

    Article  CAS  Google Scholar 

  38. Fiorino G, Manetti N, Armuzzi A et al. The PROSIT-BIO cohort: a prospective observational study of patients with inflammatory bowel disease treated with infliximab biosimilar. Inflamm Bowel Dis. 2017;23:233–243.

    Article  Google Scholar 

  39. Armuzzi A, Fiorino G, Variola A et al. The PROSIT cohort of infliximab biosimilar in IBD: a prolonged follow-up on the effectiveness and safety across Italy. Inflamm Bowel Dis. 2019;25:568–579.

    Article  Google Scholar 

  40. Gonczi L, Gecse KB, Vegh Z et al. Long-term efficacy, safety, and immunogenicity of biosimilar infliximab after one year in a prospective nationwide cohort. Inflamm Bowel Dis. 2017;23:1908–1915.

    Article  Google Scholar 

  41. Bergqvist V, Kadivar M, Molin D, et al. Switching from originator infliximab to the biosimilar CT-P13 in 313 patients with inflammatory bowel disease. Therap Adv Gastroenterol. 2018;11: ecollection.

  42. Meyer A, Rudant J, Drouin J et al. Effectiveness and safety of reference infliximab and biosimilar in Crohn disease: a French equivalence study. Ann Int Med. 2019;170:99–107.

    Article  Google Scholar 

  43. Meyer A, Rudant J, Drouin J et al. The effectiveness and safety of infliximab compared with biosimilar CT-P13, in 3112 patients with ulcerative colitis. Aliment Pharmacol Ther. 2019;50:269–277.

    Article  CAS  Google Scholar 

  44. Strand V, Balsa A, Al-Saleh J et al. Immunogenicity of biologics in chronic inflammatory bowel disease: a systematic review. BioDrugs. 2017;31:299–316.

    Article  CAS  Google Scholar 

  45. Ben-Horin S, Yavzori M, Benhar I et al. Cross-immunogenicity: antibodies to infliximab in Remicade-treated patients with IBD similarly recognize the biosimilar Remsima. Gut. 2016;65:1132–1138.

    Article  CAS  Google Scholar 

  46. Strik AS, van de Vrie W, Bloemsaat-Minekus JPJ et al. Serum concentrations after switching from originator infliximab to the biosimilar CT-P13 in patients with quiescent inflammatory bowel disease (SECURE): an open-label, multicenter, phase 4 non-inferiority trial. Lancet Gastroenterol Hepatol. 2018;3:404–412.

    Article  Google Scholar 

  47. National Health Services. The NHS saves £324 million in a year by switching to better value medicines. Available at: https://www.england.nhs.uk/2018/07/nhs-saves-324-million-year-switching-to-better-value-medicines/. Accessed February 23, 2021.

  48. Brodszky V, Rencz F, Pentek M et al. A budget impact model for biosimilar infliximab in Crohn’s disease in Bulgaria, the Czech Republic, Hungary, Poland, Romania, and Slovakia. Expert Rev Pharmacoecon Outcomes Res. 2016;16:119–125.

    PubMed  Google Scholar 

  49. Jha A, Upton A, Dunlop WC, Akehurst R. The budget impact of biosimilar infliximab (Remsima®) for the treatment of autoimmune diseases in five European countries. Adv Ther. 2015;32:742–756.

    Article  Google Scholar 

  50. Ilias A, Szanto K, Gonczi L et al. Outcomes of patients with inflammatory bowel diseases switched from maintenance therapy with a biosimilar to Remicade. Clin Gastroenterol Hepatol. 2019;17:2506–2513.

    Article  Google Scholar 

  51. Harris C, Harris R, Young D, et al. IBD biosimilar to biosimilar infliximab switching study: preliminary results. Presented at: United European Gastroenterology Week 2019; October 29–23, 2019; Barcelona, Spain.

Download references

Funding

This manuscript was not funded by any source.

Author information

Authors and Affiliations

  1. Departments of Pharmacy and Gastroenterology, Digestive Disease and Surgery Institute, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH, 44195, USA

    Shubha Bhat

  2. Division of Gastroenterology-Section of IBD, The Pennine Acute Hospitals NHS Trust, Manchester Academic Health Sciences, University of Manchester, 2.41 Fairfield House, Greater Manchester, BL9 7TD, UK

    Jimmy K. Limdi

  3. Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine, 685 W. Baltimore Street, Suite 8-00, Baltimore, MD, 21201, USA

    Raymond K. Cross

  4. Division of Gastroenterology and Hepatology, Inflammatory Bowel Disease Center, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA

    Francis A. Farraye

Authors
  1. Shubha Bhat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jimmy K. Limdi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Raymond K. Cross
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Francis A. Farraye
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shubha Bhat.

Ethics declarations

Conflicts of interest

Shubha Bhat has not conflict of interests to disclose. Jimmy Limdi has received speaker and consultancy fees from AbbVie, Arena pharmaceuticals, Galapagos, Janssen, MSD, Takeda, and Pfizer and research support from Galapagos and Takeda. Raymond K. Cross has participated in consulting and/or advisory boards, for AbbVie, Bristol Myers Squibb, Janssen, Pfizer, Samsung Bioepis, and Takeda. Francis A. Farraye has participated in advisory boards for BMS, Braintree labs, Gilead, GI Reviewers, GSK, Janssen, Pfizer, and Sebela. He is a stock owner of Innovation Pharmaceuticals. He sits on a data safety monitoring board for Lilly and Theravance.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bhat, S., Limdi, J.K., Cross, R.K. et al. Does Similarity Breed Contempt? A Review of the Use of Biosimilars in Inflammatory Bowel Disease. Dig Dis Sci 66, 2513–2532 (2021). https://doi.org/10.1007/s10620-021-07114-y

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-021-07114-y

Keywords

Search

Navigation