Biosimilars: considerations for clinical practice

Abstract

With the projected expansion of the biosimilars market, there will be an increased propensity for the substitution of reference biological products with cheaper biosimilars for economic reasons (ie, non-medical switching). This will lower the cost per patient and should provide the benefit of wider access to biological therapies. However, it is essential that patients and clinicians fully understand the rationale for non-medical switching and its potential implications in terms of efficacy, safety, and immunogenicity. To date, clinical experience supports the use of biosimilars and a growing body of evidence from clinical trials and real world observational studies specifically supports clinical decision making around non-medical switching. Equally, as non-medical switching becomes more common, it is essential that pharmacovigilance systems adapt to handle the increasing volumes of data needed to effectively monitor the use of biosimilars and detect new signals. This will require a reduced reliance on registries, as well as streamlining and integration of existing systems to allow a frequent cycle of online reporting of adverse events by healthcare professionals, analysis by national authorities, and feedback to treating clinicians. This article considers the current use and future uptake of biosimilars from a clinical perspective.

Retention Rate and Efficacy of the Biosimilar CT-P13 Versus Reference Infliximab in Patients with Ankylosing Spondylitis: A Propensity Score–Matched Analysis from the Korean College of Rheumatology Biologics Registry

“…The 4 years of follow-up, to date, in the KOBIO registry provides unique insights into long-term treatment with CT-P13 and its comparability with reference infliximab. The availability of such data may contribute to alleviating any physician concerns regarding initiating, or switching patients to, a biosimilar drug such as potential loss of efficacy, unanticipated AEs or other safety considerations, or changes in immunogenicity [ 38 ]. Since biologic therapies contribute significantly to the overall treatment cost of AS in countries, including the Republic of Korea [ 2 ], overcoming such concerns may substantially reduce the cost burden of biologic therapies in rheumatologic conditions, and increase patient access to these therapies [ 4 , 39 , 40 ].…”

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

“…Treatment failure, particularly at the individual patient level, is a concern following a non-medical switch, and discontinuation rates ranging from 0 to 87% have been reported in single-switch RW studies [ 1 , 39 – 41 ]. One reason for treatment failures after switching is tolerability issues and the emergence of new or worsening AEs, potentially caused by unanticipated differences in safety between the 2 products [ 39 , 41 , 42 ]. Treatment failures can also occur due to loss of efficacy when the biosimilar is not clinically functioning the same way as the originator product, potentially because of subtle drug- or product-related differences.…”

“…Most importantly, these effects may be amplified in the context of multiple switches. Of note, it is important to clarify that, when a patient’s disease is controlled, there is generally no expectation for improvement when switching from an originator to a biosimilar; however, based upon the current evidence, switching for non-medical reasons may carry risks such as treatment failure/discontinuation of therapy [ 1 , 39 , 40 , 42 ]. Overall, considering the large variation in discontinuation rates across the current single-switch studies, and because none of the studies meet the minimum requirements for a robust switching study, the evidence on the occurrence of treatment failures following single or multiple non-medical switches remains inconclusive [ 1 ].…”

“…Immunogenicity, mostly defined by the development of anti-drug antibodies (ADAs), is another concern when switching therapies because of a possible immune response against the different antigens (not detected during or after biosimilar development) that may be present across products, both at the drug substance and at the drug product level [ 43 – 46 ]. Although ADAs can be transient and without consequences, the persistence of ADAs can have negative effects, including loss of response, type I and type III hypersensitivity, worsening of disease, increased drug toxicity, and tolerability issues, such as injection-site or infusion reactions [ 42 , 43 , 47 ]. Several challenges and gaps remain in the assessment of immunogenicity [ 48 ].…”

A novel approach to support implementation of biosimilars within a UK tertiary hospital

“…Switching to biosimilars has been advised by NHSE with the aim that at least 90% of new patients are prescribed the best value biosimilar within 3 months of launch, and at least 80% of existing patients switch within 12 months, so that the publicly funded NHS can maximise the value it derives for patients from the money it spends on medicines . However, patients and clinicians can be concerned about potential loss of efficacy, altered immunogenicity or unanticipated differences in adverse effects when switching to a biosimilar.…”