The latest review seeking to reassure clinicians about the safety of switching their patients to biosimilars focuses on rheumatology indications.
In recent months, a multiple papers have reported on the safety of switching patients from reference biologics to cost-saving biosimilars, including a systematic literature review that found that no new safety or efficacy concerns have been detected in more than 10 years and 700 million patient days of experience with biosimilar medicines.
The latest review seeking to reassure clinicians about the safety of switching their patients to biosimilars focuses on rheumatology indications. In the paper, Piotr Wiland, MD, PhD, and colleagues explain that, unlike the United States, which has a strict definition of biosimilar interchangeability that is part of federal law, in the European context, interchangeability refers to the possibility of exchanging 1 product for another that is expected to produce the same clinical effect. In Europe, interchangeability is not regulated by the European Medicines Agency, and EU member states make take their own positions on interchangeability.
In 2015, the review notes, the Dutch medical authority issued a statement saying that exchanging biologics is acceptable if adequate clinical monitoring is undertaken and if patients have been properly informed. Also in 2015, Finland issued its own statement saying that biosimilars are interchangeable with their reference products under the care of a provider.
The authors also underscore the fact that the biosimilarity concept is rooted in comparability, which has been used for decades to show the similarity of a drug before and after a manufacturing change; thus, biosimilarity is not a new concept, and from a regulatory and scientific perspective, biosimilars and reference products are different versions of the same active substance.
The authors acknowledge that among the key discussions on biosimilars is their immunogenicity, but highlight a 2017 study appearing in BioDrugs that found that all biologics used in treating inflammatory diseases, including biosimilar infliximab, have similar levels of immunogenicity (with the exception of etanercept, a fusion protein that has lower immunogenicity than products like adalimumab or rituximab). Furthermore, multiple factors impact immunogenicity of biologics, including active inflammatory disease or concomitant use of methotrexate.
The review also highlights reassuring findings for rheumatology indications from the EGALITY study, which assessed 3 treatment switches between biosimilar and reference etanercept; the NOR-SWITCH trial, which assessed the impact of switching between reference and biosimilar infliximab on patients with a range of immune-mediated inflammatory diseases; the PLANETRA and PLANETAS studies, which assessed switching from reference to biosimilar infliximab in patients with rheumatoid arthritis and ankylosing spondylitis, respectively; and the DANBIO registry, which has collected data on patients who switched from reference to biosimilar infliximab in Denmark. In each of these cases, switching was deemed safe and effective.
Because patients may be subject to the so-called “nocebo” effect when a switch is undertaken, the authors note, patients should be made aware of and should agree to a proposed switch, they and should be properly educated about the rigor of the biosimilar approval process in order to instill confidence in their treatment.
Finally, say the authors, while data on multiple switches between a reference and biosimilar are limited, the literature demonstrates that a single switch is not associated with any significant risk. Long-term observational studies and patient monitoring in registries will provide further data on multiple switches and will contribute to the growing body of knowledge on the feasibility of switching.
Wiland P, Batko B, Brzosko M, et al. Biosimilar switching—current state of knowledge. Rheumatologica. 2018;56(4):234-242. doi: 10.5114/reum.2018.77975.