Bioequivalence studies with anti-TNF biosimilars

ABSTRACT

Introduction: Biosimilars, as defined by the European Medicines Agency, have been used in Europe since 2006. The landscape was considerably expanded when the first biosimilar of a monoclonal was approved and introduced in the European market. CT-P13 was developed by Celltrion as an infliximab biosimilar in 2013, not without controversy. As these complex molecules cannot be completely identical, some experts, clinicians, and even patients were skeptical regarding the real bioequivalence of the drugs. Currently, several new infliximab and adalimumab biosimilars are available or will reach the market in a few months.

Areas covered: Our goal is to review, mainly from a clinical perspective, the available evidence for bioequivalence of anti-TNF biosimilars. We aim to take into account not only preclinical studies, mostly done for regulatory issues, but also data from clinical studies.

Expert opinion: We can conclude that bioequivalence with originator is well demonstrated in those drugs which have followed European Medicines Agency regulatory pathways. Switching from originator to biosimilar appears safe for all indications. However, there are few data available for switching from one biosimilar to another, or for complete interchangeability. Prospective studies and strict pharmacovigilance are recommended.

KEYWORDS:

• Infliximab
• adalimumab
• biosimilar
• bioequivalence
• switching
• anti-TNF

Article highlights

• Biosimilars to antiTNF biologics approved by EMA and/or FDA have demonstrated bioequivalence in all available studies.

• Immunogenicity of biosimilars has not been proven different to originators.

• Switching from originator to biosimilars has been found to be safe and effective in several studies.

• Multiple switching between different biosimilars and originator cannot be recommended with available data.

• No unexpected safety issues have appeared after several years of biosimilars use.

• Biosimilars approved by EMA are a good alternative and do contribute to containing costs for the system.

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Declaration of interest

M Gimeno-Gracia has received payments for lectures from Jannsen, Gilead and Roche. CJ Gargallo has received payments for lectures from Takeda and Shire. She has also grant ‘Juan Rodes’ from the Institute Carlos III of Spain. F Gomollon has received payments for lectures from Abbvie, Takeda, and Janssen; and research grants (for the institution) from MSD. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.