Comparative efficacy, safety and immunogenicity of biosimilars and their reference biologic drugs in ankylosing spondylitis: a systematic review and meta-analysis of randomized controlled trials.

Abstract

Introduction: This systematic review and meta-analysis aimed to compare the efficacy, safety, and immunogenicity of biosimilars and reference biologics (adalimumab, etanercept, infliximab) in the treatment of ankylosing spondylitis (AS).

Methods: We conducted a systematic search of four electronic databases through 6 January 2025, supplemented by trial registry searches for unpublished trials. We included head-to-head randomized controlled trials (RCTs) that compared biosimilars with reference biologics in patients with AS. Effect measures were summarized using random-effects meta-analysis, and the risk of bias was assessed using the Cochrane RoB 2 tool. The overall certainty of evidence was assessed using the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) system.

Results: Six head-to-head RCTs (2,107 participants) were included. Biosimilars demonstrated similar efficacy to reference biologics in achieving ASAS20 (risk ratio [RR] 1.01, 95% confidence interval [CI] 0.96-1.07) and ASAS40 (RR 1.00, 95% CI 0.94-1.05) responses. No significant differences were observed in other efficacy (e.g. disease activity indices), safety (e.g. adverse events), or immunogenicity outcomes (e.g. anti-drug antibodies). Sensitivity and subgroup analyses confirmed the robustness of these findings.

Conclusions: This study provides evidence supporting the clinical equivalence of biosimilars to reference biologics in AS treatment, reinforcing their potential as safe and effective alternatives.

Protocol registration: www.crd.york.ac.uk/prospero identifier is CRD42024528886.