The Challenges of Switching Therapies in an Evolving Multiple Biosimilars Landscape: A Narrative Review of Current Evidence

Abstract

With the increasing availability of biosimilars, the practice of switching therapies for non-medical reasons between an originator biologic and an analogous biosimilar has become more common. The evidence to support this practice mostly comes from single-switch randomized controlled trials (RCTs) and real-world (RW) evidence studies. However, as more biosimilars of the same originator enter the market, multiple switching events between originators and biosimilars is becoming a reality, despite limited evidence to support the efficacy and safety of such practice. Some countries have established guidelines, policies, or laws related to interchangeability and/or automatic substitution, whereas others have left these practices unregulated or controlled by other components of the healthcare system. Collectively, guidelines on single non-medical switching are often vague, with even less focus given to multiple non-medical switching, leaving this practice mostly unregulated. This narrative review will first discuss the current regulatory perspectives on non-medical switching and challenges associated with switching therapies, particularly with the availability of multiple biosimilars. We will then review the current evidence from RCTs and RW studies in the light of three different multiple-switch scenarios currently taking place in clinical practice: switching between an originator and a single biosimilar, switching between biosimilars of the same originator, and the clinical practice of switching back to the originator (i.e., switchbacks) after a failure of the initial non-medical switch to the analogous biosimilar.

Safety, Immunogenicity and Interchangeability of Biosimilar Monoclonal Antibodies and Fusion Proteins: A Regulatory Perspective

“…However, immunogenicity is often presented as the main and unpredictable risk of biosimilars in spite of the questionable theoretical basis and lack of any supporting clinical evidence for this hypothesis [13,38,41]. Furthermore, much of the discussion on interchangeability has been focused on the requirement for extensive studies with multiple switches, as well as switches between biosimilars of the same reference product [39][40][41][42][43][44][45][46][47][48][49][50][51]. Such studies would require hundreds of patients per study, which will discourage the development of biosimilars [32,41].…”

Biological Therapies for Rheumatoid Arthritis: An Overview for the Clinician

“…With the increasing availability of biosimilars clinicians should be mindful that multi-switching between biosimilars, and switchbacks from biosimilar to bio-originators, is less well-studied at present. 29 …”

Letter to the Editor Regarding “The Challenges of Switching Therapies in an Evolving Multiple Biosimilars Landscape: A Narrative Review of Current Evidence”

“…We read the article by Feagan and colleagues discussing potential challenges of biologic switching with considerable interest [ 1 ]. Although we agree with Feagan et al that high-quality clinical and postmarketing studies should be conducted to improve our understanding of potential switching effects, we believe that several additional factors should be considered when discussing biosimilar use and switching.…”