Drug Discontinuation in Studies Including a Switch From an Originator to a Biosimilar Monoclonal Antibody: A Systematic Literature Review

Abstract

Purpose: In observational studies of patients switched from stable treatment with an originator monoclonal antibody (mAb) to a biosimilar, higher rates of biosimilar discontinuation versus those observed in blinded switching studies have been reported. Because this observation relates to the real-world setting, it has been suggested that switching outside of clinical trials may be associated with nocebo effects. However, real-world data on drug discontinuation and nocebo effects after switching to mAb biosimilars remain limited. This systematic review collated information from switching studies regarding discontinuation rates of biosimilar mAbs and investigated the subjectivity of reasons for discontinuation to determine the impact of potential nocebo responses.

Methods: MEDLINE (via PubMed), EMBASE, Cochrane Library, and abstract databases of selected congresses were screened for reports of mAb switching studies with a minimum post-switch follow-up ≥6 months and accessible information on discontinuation rates.

Findings: A total of 14 observational studies were included, all of which involved a switch to CT-P13. Ten interventional studies involving a switch to other biosimilar mAbs were excluded from the analysis because nocebo effects relate to the observational setting only. Eleven studies (78.6%) reported biosimilar discontinuation rates that were higher than expected based on data pertaining to long-term use of the originator infliximab and clinical trials involving a switch to CT-P13 (>10% per year; range, 12.2%-28.2%). Eight studies attributed a proportion of discontinuations to subjective disease worsening or subjective adverse events. Subjective adverse event reports were identified in 7 of the observational studies.

Implications: Discontinuation rates of biosimilar mAbs may increase due to subjective effects after switching from an originator mAb. These findings highlight the need for further patient education and well-designed, observational switching studies as well as the collection and analysis of identifiable pharmacovigilance and postmarketing data of biologics, including biosimilars. The collection of real-world results is particularly pertinent for mAbs other than CT-P13, for which there is currently a lack of observational switching data.

Keywords: biologics; biosimilars; nocebo; real-world; switch.