Biosimilars: Is It Safe to Switch?

Jonathan Kay, MD


January 14, 2014

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Hello. I'm Jonathan Kay, Professor of Medicine and Director of Clinical Research in the Division of Rheumatology at UMass Memorial Medical Center and the University of Massachusetts Medical School, both in Worcester, Massachusetts. Welcome to my Medscape blog.

I have previously spoken about biosimilar medications as a therapeutic option in the future. Well, biosimilars are now here and ready to use in the European Union. On June 27, 2013, the Committee for Medicinal Products for Human Use of the European Medicines Agency recommended approval of Celltrion's biosimilar to infliximab, CT-P13. On September 10, 2013, the European Commission approved this medication for human use. It is now marketed by Hospira as Inflectra™ and by Celltrion as Remsima™; and it is now available in Ireland, Portugal, Norway, and Finland. When the patent expires in 2015, this medication will become more widely available in the European Union countries. The patent for infliximab lasts several years longer in the United States, so we will probably not be seeing biosimilar infliximab for several years after the Europeans are beginning to use this compound.

A concern about biosimilars is that of switching or interchangeability. Switching means transitioning between the reference product and the biosimilar. Interchangeability refers to switching back and forth between the reference product and the biosimilar, often without the knowledge of the prescribing physician. The Biologics Price Competition and Innovation Act of 2009 has a pathway that suggests that interchangeability could be proven by a clinical trial that shows no loss of efficacy and no increase in adverse events with repeated switching between the biosimilar and the reference compound.

The clinical trial designed to prove this is somewhat controversial. The experimental group would have to be switched repeatedly, at least twice and perhaps more often, between the reference product and the biosimilar, whereas the control group would be treated with the reference product or the biosimilar alone. The potential risk to the experimental group would be loss of efficacy and increased safety concerns that might prevent treatment in the future with either the reference product or the biosimilar, whereas this would not be a concern for the control group. Thus, there would be an infinite risk to the experimental group, making this clinical trial design impractical for execution and probably never approved by an institutional review board.

At the recent American College of Rheumatology annual meeting, Professor Yoo[1] from South Korea presented data from a long-term extension of CT-P13 in which patients were switched from the reference product, infliximab, to CT-P13 and maintained for the remainder of 104 weeks on the biosimilar. This group showed no loss of efficacy or increase in immunogenicity compared with those who had been treated from the start with the biosimilar compound. This clinical trial, which was presented as a late-breaking abstract at the American College of Rheumatology meeting, suggests that switching or transitioning from the reference product to the biosimilar will be safe, but it does not provide any evidence to support interchangeability. Interchangeability remains a controversial area, and future studies will tell whether this will ever become a reality.

The infliximab biosimilar CT-P13 was approved by the European Commission for all indications for which the reference product infliximab is approved. Thus, extrapolation of indications is something that is now a reality for biosimilars. We look forward to seeing future developments in the world of biosimilars, and I hope to report to you about them on future blogs on Medscape.

Thank you for your attention. I look forward to seeing you again on Medscape.


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