Comparative Safety Profiles of Biosimilars vs. Originators Used in Rheumatology: A Pharmacovigilance Analysis of the EudraVigilance Database

Abstract

Background: The advent of biosimilars has revolutionized the management of conditions like rheumatoid arthritis by offering cost-effective alternatives to expensive biologics. Objectives: This study aims to compare the post-marketing safety profiles of biosimilars used in rheumatology with their respective reference products (RPs). Methods: Data were retrieved from EudraVigilance for biosimilars of adalimumab, etanercept, infliximab, and rituximab, and compared with their RPs. Our analysis focused on biosimilars authorized before 2021, using data from January 2021 to December 2023. We conducted a descriptive analysis of suspected adverse events, categorized using the Medical Dictionary for Regulatory Activities, and performed a comparative analysis using the reporting odds ratio to identify potential safety signals of disproportionate reporting. Results: We analyzed 75,327 reports, identifying 566,249 drug-event pairs. The results indicate that biosimilars have safety profiles largely comparable to their RPs. Female patients predominated in the reports, representing 69.4% of RPs and 56.9% of biosimilars. Notably, biosimilars demonstrated higher reporting rates for non-serious suspected adverse drug events (AEs), such as injection site pain, arthralgia, and fatigue. Specific AEs, including drug ineffectiveness and off-label use, were more frequent for infliximab and etanercept biosimilars, possibly reflecting real-world usage patterns and nocebo effects. Serious AEs, including malignancies and immunological reactions, were also noted, underscoring the necessity for ongoing monitoring. Conclusions: Our findings suggest that biosimilars are safe alternatives to RPs, contributing to significant healthcare cost savings in the EU. This study underscores the need for ongoing pharmacovigilance and long-term safety research to validate the clinical use of biosimilars in rheumatology.

Keywords: adalimumab; biosimilars; etanercept; infliximab; pharmacovigilance; post-marketing; rheumatology; rituximab; safety.

Figure 1

Number of ICSRs for adalimumab, etanercept, infliximab, and rituximab biosimilars in 2021, 2022, and 2023.

Figure 2

Number of ICSRs for adalimumab (Humira^®), etanercept (Enbrel^®), infliximab (Remicade^®), and rituximab (MabThera^®) originators in 2021, 2022, and 2023.