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Biosimilars in rheumatology: current perspectives and lessons learnt

This article has been updated

Key Points

  • Biosimilars are biopharmaceuticals that have been assessed by regulatory agencies to have efficacy and safety similar to their reference products and are expected to be marketed at substantially lower prices

  • CT-P13 (an infliximab biosimilar) was the first monoclonal antibody biosimilar to be approved, but not all national regulatory agencies granted extrapolation to all infliximab indications

  • A substantial proportion of patients treated with biopharmaceuticals develop antidrug antibodies, regardless of whether they received a biosimilar or the reference product

  • Establishing a nomenclature system that facilitates traceability for the purpose of pharmacovigilance is a key issue in the adoption of biosimilars in clinical practice

  • Extrapolation of indications for biosimilars is possible, but concerns have been raised regarding the potential efficacy and safety of a biosimilar in diseases for which it has not been studied

Abstract

Biosimilars, based on biopharmaceuticals approved by regulatory agencies that are no longer under patent protection, have efficacy and safety comparable to their reference products, and are a new therapeutic option to treat inflammatory diseases. Biosimilars must be distinguished from 'biomimics' or 'biocopies', which are marketed in some countries but have not been evaluated according to the stringent regulatory pathway used for biosimilars. CT-P13, based on infliximab, was the first biosimilar approved for the treatment of inflammatory diseases; however, some countries did not allow extrapolation of indications to all eight diseases for which the reference drug infliximab is approved. Antidrug antibodies can reduce drug levels and affect clinical efficacy, but although available data suggest that biosimilars and their reference products have comparable immunogenicity, this important property might differ between individual biopharmaceuticals. This Review discusses biosimilars already approved within the past 3 years to treat rheumatic diseases, as well as others that are currently under development. The main challenges posed by biosimilars are also addressed, such as the extrapolation of indications to diseases only studied for the reference drug, and the definition of strategies for adequate pharmacovigilance to monitor biosimilars after marketing approval.

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Figure 1: Mechanisms of protein diversity and consequences for the immune system.
Figure 2: EMA guidance on biosimilar mAbs: a stepwise approach.
Figure 3: ADA induction after treatment with infliximab or CT-P13.
Figure 4: Study design to compare the efficacy of reference drugs and biosimilars.

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Change history

  • 25 August 2015

    In the version of this article initially published online, the line colours in Figure 4 were incorrect. The error has been corrected for the print, HTML and PDF versions of the article.

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Both authors contributed equally to all aspects of the manuscript, including researching data for the article, discussions of its content, writing, review and editing of the manuscript before submission.

Corresponding author

Correspondence to Thomas Dörner.

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Competing interests

T.D. declares that he has received honoraria for study support and consultations from Hospira, Johnson & Johnson, Merck Sharp & Dohme, Pfizer, Roche/Chugai, Samsung, Sanofi and UCB. J.K. declares that he has received research support (paid to the University of Massachusetts Medical School) from AbbVie, Genentech, Pfizer and Roche Laboratories, and honoraria for consultations from Amgen, AbbVie, Boehringer Ingelheim, Bristol–Myers Squibb, Epirus Biopharmaceuticals, Genentech, Hospira, Janssen Biotech, Merck Sharp & Dohme, Nippon Kayaku, Novartis Pharmaceuticals, Pfizer, Samsung Bioepis, Roche Laboratories and UCB.

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Dörner, T., Kay, J. Biosimilars in rheumatology: current perspectives and lessons learnt. Nat Rev Rheumatol 11, 713–724 (2015). https://doi.org/10.1038/nrrheum.2015.110

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