New Evidence Confirms Safe Biosimilar-to-Biosimilar Switching

A literature review of primarily European data evaluating switching patients from a biosimilar to another biosimilar revealed new data establishing the safety and efficacy of biosimilar-to-biosimilar switching.¹

Biosimilars are now widely accepted as alternatives to reference biologics in areas like immune-mediated diseases and oncology. By December 2023, more than 90 biosimilars were approved in the EU and more than 40 in the USA. Many molecules, including infliximab and adalimumab, have multiple approved biosimilars, making switching between them common.

Since the July 2022 publication of the first systematic review of biosimilar-to-biosimilar switching, the European Medicines Agency and the European Heads of Medicines Agencies have issued statements supporting the safety and efficacy of such switching.² The US FDA's systematic review and meta-analysis also found no safety or immunogenicity differences between patients who switched biosimilars and those who did not.

However, there remains skepticism globally about the safety of switching between biosimilars, particularly in gastroenterology and ophthalmology spaces. Additionally, the US continues to have interchangeability designations, which have been a significant source of controversy and confusion about whether biosimilars without this label are as safe as the ones that do.

To add to the current body of evidence, researchers conducted a second search encompassing biosimilar-to-biosimilar switching studies from January 1, 2022, to December 31, 2023. Multiple approaches ensured studies were counted only once, even if outcomes were published in several articles or abstracts. The systematic search used electronic databases and expanded MeSH keywords to include all relevant biological drugs available in the USA, EU, Canada, and Australia. Additional searches included hand searching cited publications and examining three other systematic reviews to identify any further studies.

As of December 31, 2023, 31 observational studies on biosimilar-to-biosimilar switching with efficacy and safety data have been published, involving 6081 patients. Most studies focused on infliximab, with some on adalimumab, rituximab, or etanercept, covering conditions like rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, and inflammatory bowel disease.

Eight new studies were identified in addition to the 23 from the earlier review, including 6 full publications and 2 congress abstracts. Five abstracts from the previous review were later published as full articles. Additionally, 1 study from another review was included, which was not in the initial review or detected in the current systematic search.

Switching between biosimilars for infliximab and adalimumab proved effective and well-tolerated. In patients with sarcoidosis, the switch from Remicade or Inflectra to Flixabi, all of which are infliximab biosimilars, showed no discontinuations or significant clinical changes within 6 months. In patients with IBD, switching from Flixabi to Inflectra resulted in a 9.4% discontinuation rate, mainly due to immunogenicity and loss of response, but persistence was higher with fewer switches. Another study showed an 86.4% treatment persistence over 13 months when switching from CT-P13 to SB2. A psychometric study found no significant changes in outcomes, indicating safety and efficacy.

For adalimumab, switching between biosimilars (ABP501 to GP2017 and MSB11022 to GP2017) maintained stable remission rates and high drug survival. In patients with chronic inflammatory arthritis, switching from ABP501 to SB5 showed no significant changes in disease activity, though some discontinued due to lack of efficacy or adverse events. A study of 72 patients with IBD switching to GP2017 showed high remission rates and drug persistence with no serious adverse events.

Large-scale studies like DANBIO and PERFUSE supported these findings, showing stable disease activity and high retention rates with no significant safety concerns. Overall, switching between biosimilars for infliximab and adalimumab was safe, effective, and maintained stable clinical outcomes.

The study had some limitations, including reliance on observational data, with significant insights from the DANBIO registry. Most research focused on infliximab and adalimumab due to their early adoption. The small sample sizes in many studies might limit their standalone conclusions, although they align with larger studies. Additionally, some studies were only published as abstracts, which typically provide less data than full peer-reviewed articles.

References

1. Cohen HP, Bodenmueller W. additional data in expanded patient populations and new indications support the practice of biosimilar-to-biosimilar switching. BioDrugs. 2024;38(3):331-339. doi:10.1007/s40259-024-00655-4

2. Cohen HP, Hachaichi S, Bodenmueller W, Kvien TK, Danese S, Blauvelt A. Switching from one biosimilar to another biosimilar of the same reference biologic: a systematic review of studies. BioDrugs. 2022;36:625-637. doi:10.1007/s40259-022-00546-6