Title:Biosimilars: From Extrapolation into Off Label Use
Volume: 23
Issue: 44
Author(s): Sizheng Zhao, Jagdish R. Nair and Robert J. Moots*
Affiliation:
- Department of Rheumatology, Aintree University Hospital, Liverpool,United Kingdom
Keywords:
Biosimilar, extrapolation, off-label, monoclonal antibody, anti-TNF, rheumatoid arthritis, ankylosing spondylitis.
Abstract: Background: Biologic drugs have revolutionised the management of many inflammatory conditions.
Patent expirations have stimulated development of highly similar but non-identical molecules, the biosimilars.
Extrapolation of indications is a key concept in the development of biosimilars. However, this has been met with
concerns around mechanisms of action, equivalence in efficacy and immunogenicity, which are reviewed in this
article.
Methods: Narrative overview composed from literature search and the authors' experience. Literature search
included Pubmed, Web of Science, and online document archives of the Food and Drug Administration and
European Medicines Agency.
Results: The concepts of biosimilarity and extrapolation of indications are revisited. Concerns around extrapolation
are exemplified using the biosimilar infliximab, CT-P13, focusing on mechanisms of action, immunogenicity
and trial design. The opportunities and cautions for using biologics and biosimilars in unlicensed inflammatory
conditions are reviewed.
Conclusions: Biosimilars offer many potential opportunities in improving treatment access and increasing treatment
options. The high cost associated with marketing approval means that many bio-originators may never become
licenced for rarer inflammatory conditions, despite clinical efficacy. Biosimilars, with lower acquisition cost,
may improve access for off-label use of biologics in the management of these patients. They may also provide opportunities
to explore off-label treatment of conditions where biologic therapy is less established. However, this potential
advantage must be balanced with the awareness that off-label prescribing can potentially expose patients to
risky and ineffective treatments. Post-marketing surveillance is critical to developing long-term evidence to provide
assurances on efficacy as well as safety.
