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.

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a systematic search of four electronic databases through 6 January 2025, supplemented by trial registry searches for unpublished trials.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.