Biosimilar-to-biosimilar switching safe, effective in rheumatology
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Although biosimilar-to-biosimilar switching is not covered by health regulations or guidance, a systematic literature review suggests the practice is safe and effective, according to data published in BioDrugs.
“As the biosimilar market continues to develop, there are often multiple biosimilars approved to a given reference biologic,” Hillel P. Cohen, PhD, of Sandoz, in Princeton, New Jersey, the lead author of the study, told Healio. “As a result, after patients transition from a reference biologic to a biosimilar, there is also a possibility that they might be subsequently switched to another biosimilar to the same reference biologic.”
“Some health care providers are hesitant to switch patients from one biosimilar to another biosimilar because of a perceived lack of clinical data on such switches,” he added.
To investigate the safety and feasibility of biosimilar-to-biosimilar switching, Cohen and colleagues conducted a systematic review. The researchers searched through December 2021 in databases including Biosis, Embase, MEDLINE and the EBM Reviews/Cochrane Database of Systematic Reviews via Ovid. A biosimilar was included in the search and analysis if itself or another biosimilar version of their common reference drug was previously approved in the United States or European Union.
Once potential studies were identified, they were individually evaluated regarding the presence of safety or effectiveness data stemming from switching biosimilars. Inclusion criteria were expansive to allow the researchers to gather as much relevant data as possible, the authors wrote. Research from non-English publications, papers detailing non-human studies, editorials, comments and brief surveys were excluded from the analysis.
The initial screening was based on title and abstracts, and included all studies mentioning biosimilar-to-biosimilar switching. The researchers then collected data from the full publications, including trial designs, patient demographics, safety results, effectiveness and immunogenicity. Additionally, the researchers evaluated the inclusion of adverse events.
In total, after further evaluation of specific papers, the authors analyzed 23 studies. Of those, 13 were published in peer-reviewed papers, and the rest were published as abstracts. The selected papers included a total of 3,657 patients. All included studies were observational. The majority of included studies examined infliximab (Remicade, Janssen) switches, but adalimumab (Humira, AbbVie), etanercept (Enbrel, Amgen) and rituximab (Rituxan, Genentech) were also regarded, the authors wrote.
Overall, published data “suggests that biosimilar-to-biosimilar switching is a safe and effective clinical practice,” Cohen and colleagues wrote.
In one analyzed study investigating swaps from infliximab to its biosimilar in patients with inflammatory bowel disease, 10.8% of patients reported a loss of effectiveness, the authors reported. A switch to the biosimilar was successful in 82% of patients with Crohn’s disease receiving adalimumab. Additionally, rituximab swaps were found to be safe and efficacious, the authors concluded.
“Rheumatologists now realize based on extensive, previously published data that patients can be transitioned from reference biologics to biosimilars without impacting safety or effectiveness,” Cohen said. “There is no scientific reason to expect that there would be clinically relevant differences if there are biosimilar-to-biosimilar switches, and this was confirmed in the results of our review.
“The results from our review reveal that rheumatologists should have confidence that the data demonstrate that safety and effectiveness are not impacted if patients switch from one biosimilar to another biosimilar of the same reference biologic,” Cohen added.
Perspective
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Transitions from a reference biologic to a biosimilar, or from one biosimilar to another, are often the consequence of insurance mandates, pharmacy benefit formulary adjustments or limitations to reduce costs. The possibility of multiple switches between biosimilars of the same reference biologic is already a reality, and these types of switches are expected to become more common in the future. The term “cross switching” has been proposed to refer to this practice of switching between biosimilars of the same reference biologic.
Here is an extensive systematic review performed of published biosimilar-to-biosimilar switch studies, identifying 23 studies that met criteria for inclusion and analysis. The objective of these analyses was to evaluate clinical outcomes from studies relevant to biosimilar-to-biosimilar switching. All citations chosen for inclusion were from published observational studies.
In studies that looked at biosimilar-to-biosimilar switches with infliximab (Remicade, Janssen) reference product to biosimilar, and biosimilar-to-biosimilar, followed for 12 months, and found there was no loss of clinical responses. The loss of response rate was –15%, within statistically significant differences in those who switched from reference infliximab to one biosimilar, or from one biosimilar to another infliximab biosimilar. The presence of antidrug antibodies was found in 4% of patients in either the single or double switch group.
The French PERFUSE study looked at patients with axial spondyloarthritis, rheumatoid arthritis and psoriatic arthritis over 12 months while they were treated with biosimilar infliximab or transitioned from the reference infliximab to another biosimilar, and found no loss of disease control. A 2015 Danish study of 780 RA, PsA and axial SpA patients completed the first switch. Patients were treated with reference infliximab for a median of 7 years before switching.
At 1 year, 83% maintained biosimilar treatment. In 2019, 52% of these patients were still on treatment and were switched to another biosimilar, and at 1 year 91% of these patients were maintained on this treatment.
Biosimilar-to-biosimilar switch studies of etanercept (Enbrel, Amgen) biosimilars concluded the retention rate was close to 90% 6 months after the final switch from the reference product to one biosimilar, then to another biosimilar.
Urru and colleagues assessed the safety of switching between a rituximab (Rituxan, Genentech) biosimilar in a prospective observational study in patients with non-Hodgkin’s Lymphoma and chronic lymphocytic leukemia. Findings from this study support the position that switching between rituximab biosimilars is safe and does not lead to loss of efficacy. No safety signals emerged with the use of a specific biosimilar or with the practice of switching.
The present systematic analysis indicates there were no clinically meaningful differences in safety or effectiveness up to 12 months between two biosimilars of the same reference biologic for infliximab, adalimumab, etanercept or rituximab.
Perspective
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Now that biosimilars have become a part of our everyday rheumatology practice, we have become more comfortable in reassuring our patients of the safety and efficacy of switching from the reference product to the biosimilar. However, with the current influx of several different approved biosimilars to the same reference product, there is an added level of stress and confusion for both the patient and the provider. There are limited data on the outcomes of switching between various biosimilars, making it more difficult for us to confidently provide this reassurance.
Furthermore, these decisions are often not made by the provider, but rather driven by a formulary, thus adding to the patient’s anxiety regarding their treatment plan. Although the review conducted by Cohen and colleagues seems to demonstrate the safety and efficacy of these biosimilar-to-biosimilar switches, it is an important reminder for us, as providers, to discuss the possibility of these changes with patients at the onset of treatment so that patients can feel more confident in their treatment decisions.
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