As Evidence Base for Biosimilars Grows, So Too Will Confidence in Switching, Review Says

Despite potential benefits of biosimilar adoption in terms of both patient access and healthcare system sustainability, and despite ongoing efforts at patient and provider education on biosimilars, stakeholders may continue to have concerns about perceived risks with switching. A new review of the available literature on switching—from randomized controlled trials and real-world evidence—sought to address those concerns, and said that additional education and ongoing real-world evidence collection will be necessary to increasing stakeholder comfort with these agents.

The authors highlighted the fact that potential immunogenicity is an often-cited concern among patients and physicians, but pointed out that the majority of clinical trials have not reported any changes in immunogenicity following a switch. Changes to delivery devices for those patients who self-administer their biologic therapy have also been a stated concern, but the authors point out that a number of studies have shown that biosimilar makers have introduced device innovations that are actually preferred by patients and providers.

The authors also discussed findings from 25 randomized controlled trials completed to date that have included a switch arm for biosimilars that treat inflammatory diseases. These trials, which investigated switches to biosimilars of etanercept, adalimumab, infliximab, and rituximab, have not raised concerns about safety or efficacy of the biosimilars. Some of these studies have not had adequate statistical power to detect differences between switched versus continuously treated groups, however, or have lacked a comparator arm that included patients receiving continuous therapy with the reference drug.

The review also examines 3 studies of multiple switches, 2 of which were randomized phase 3 trials. These trials evaluated biosimilar etanercept (Erelzi) and adalimumab (Hyrimoz) versus their references, and in both trials, a proportion of enrolled patients receiving either the biosimilar or the reference underwent 3 switches between the products. Neither trial found an impact on safety, immunogenicity, or efficacy. The third study, an open-label extension of a phase 3 study of a different adalimumab biosimilar (Idacio), included a rerandomization at week 24 in which two-thirds of patients continued on either the biosimilar or the reference treatment and one-third switched to the alternative treatment. After 28 weeks, all patients received the biosimilar for a further 48 weeks. Comparable safety, efficacy, and immunogenicity were all reported.

Real-world evidence has also supported switching to biosimilars; the authors point to 53 observational studies of a switch to biosimilar infliximab (Inflectra, Remsima) that did not identify any significant risks associated with a single switch. They also highlight the DANBIO registry study evaluating the use of biosimilar etanercept (Eticovo, Benepali) that found that disease activity remained stable for patients who switched to the biosimilar, and that no major safety events occurred in patients who switched.

On the basis of data like these, say the authors, multiple medical societies have begun to recommend the use of biosimilars, including the implementation of switching: the European Crohn’s and Colitis Organisation, several rheumatology societies, and the British Association of Dermatology have all expressed their support for prescriber-led switching when conducted in consultation with the patient. As the evidence base grows, so too will confidence, write the authors. Even so, there remains a need for more education in order for physicians to feel comfortable with biosimilars; the authors call on biosimilar manufacturers to engage with clinicians to build credibility and trust.

Finally, the authors emphasize the need for patient information, including educating patients on the societal benefits of switching, such as expanded access. Reliable codes of practice will also help build confidence among patients, the authors write, and patient stratification using tools like the Beliefs About Medicine Questionnaire may help determine which kinds of information individual patients need.

Reference

Edwards C, Hercogová J, Albrand H, Amoit A. Swtiching to biosimilars: current perspective in immune-mediated inflammatory diseases. Expert Opin Biol Ther. 2019;6:1-14. doi: 10.1080/14712598.2019.1610381.