Comparative effectiveness and safety of biosimilars versus reference biologics in rheumatoid arthritis during treatment initiation: a systematic review of real-world evidence

Abstract

Background: Effective management of rheumatoid arthritis (RA) often requires the use of biological disease-modifying antirheumatic drugs (bDMARDs). Biosimilar drugs (biosimilars), licensed pharmaceutical products that exhibit high similarity to their reference biological products (originators), have emerged as more affordable alternatives.

Aim: To compare the real-world effectiveness and safety of biosimilars and originators of bDMARDs in the management of RA at treatment initiation.

Method: A systematic literature search was conducted using PubMed, MEDLINE, Embase, Scopus, International Pharmaceutical Abstract and CINAHL from database inception to 18th April 2025. Observational studies utilising real-world data (e.g., electronic health records, biologics registries) that compared clinical outcomes between patients initiating treatment with either a biosimilar or an originator for RA were included. Quality assessment was conducted using the Newcastle-Ottawa Scale (NOS) and a narrative synthesis was conducted to summarise key findings.

Results: A total of 13 retrospective cohort studies were included, providing data on 34,280 patients initiating treatment with bDMARDs for RA. Treatment retention was the most investigated effectiveness outcome (n = 11), and all studies found that biosimilars were associated with comparable retention profiles compared to originators. No significant differences were identified for other effectiveness outcomes (e.g., disease activity indices). For safety outcomes, adverse events (AEs) were documented in eight studies. However, seven of these studies were of poor quality in assessing safety outcomes due to inadequate control for confounding factors.

Conclusion: In real-world settings, biosimilars generally demonstrate comparable effectiveness to originators. Future investigations are warranted to examine the comparative safety profiles of biosimilars and originators.

Keywords: Biologics; Biosimilars; Real-world evidence; Rheumatoid arthritis.