Regulators licensed the 3 etanercept biosimilars discussed for all of the indications of the reference drug on the basis of the extrapolation of indications, a practice that the authors say rheumatologists may find “anomalous and a source of debate.”
A newly published review appearing in Biologics: Targets and Therapy discusses the existing literature on 3 biosimilar etanercept products: Benepali (developed by Samsung Bioepis and licensed in multiple non-US regions, sold in some areas under the name Brenzys), Erelzi (developed by Sandoz and approved in the United States and other regions), and Davictrel (developed by Hanwha Chemical Corporation and licensed in the Republic of Korea).
The review’s authors explain that the bioequivalence of each of the 3 products to the reference etanercept was demonstrated through pharmacodynamic and pharmacokinetic studies, as well as in head-to-head trials. Additionally, they write, regulators licensed the biosimilars for all of the indications of the reference drug on the basis of the extrapolation of indications, a practice that the authors say rheumatologists may find “anomalous and a source of debate.”
The authors point out that consensus documents from the European League Against Rheumatism deem switching from the reference drug to the biosimilar to be safe and effective, that a switch may be undertaken in consultation with the patient. However, they write, evidence on efficacy and safety of nonmedical switching “is mostly based on a few observational, short-term studies on a small number of participants, thus seeming largely insufficient to recommend this procedure.”
They add that, in reported studies on nonmedical switching from the reference etanercept to the biosimilar resulted in discontinuation related to adverse events or loss of efficacy in 9% to 17% of patients. The authors state that this may be due to the fact that patients with treated in real-world practice may have significant differences from patients who were eligible for clinical trials.
The authors go on to say that biosimilars have “caught both physicians and patients by surprise,” and point to a German survey of 50 rheumatologists, which found that 95% of the clinicians who responded would prefer to use a reference product first, as an illustrative example. They also suggest that lack of patient education could be linked to the so-called “nocebo” effect, or negative outcomes linked with negative expectations about a drug. However, they write, because the nocebo effect is an undefined condition, it is challenging to address.
The authors conclude that biosimilar etanercept can be recommended as a first treatment, but that further evidence on switching to a biosimilar from the reference “would be preferable.”
Cantini F, Benucci M. Focus on biosimilar etanercept—bioequivalence and interchangeability. Biologics. 2018;12:87-95. doi: 10.2147/BTT.S126854.