The Efficacy and Safety of Intravenous Tocilizumab to Treat Graves' Ophthalmopathy: A Systematic Review and Single-arm Meta-analysis

Abstract

Purpose: This study aims to evaluate the efficacy and safety of intravenous (IV) tocilizumab (TCZ) in the treatment of Graves' ophthalmopathy (GO).

Methods: A comprehensive search was conducted across the Web of Science, PubMed, Embase, Cochrane Library, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov databases from inception to April 2024. Randomized controlled trials and cohort studies that used IV TCZ for treating GO were included.

Results: Twelve studies encompassing 219 patients with active, steroid-resistant GO were analyzed. The meta-analysis demonstrated significant improvements in Clinical Activity Score (CAS) response (effect size [ES] = 0.98; 95% confidence interval [CI], 0.93-1.00), proptosis response (ES = 0.50; 95% CI, 0.27-0.73), and diplopia response (ES = 0.48; 95% CI, 0.24-0.74). The ES for adverse events was 0.27 (95% CI, 0.22-0.33), with only 3 severe cases necessitating treatment discontinuation, and a low reactivation rate (ES = 0.01; 95% CI, 0.00-0.04). TCZ treatment led to a mean CAS reduction of 4.60 points (95% CI, 3.88-5.32) across 10 studies, a mean proptosis reduction of 2.04 mm (95% CI, 1.42-2.65) across 7 studies, and a mean decrease in TSH receptor antibodies levels of 10.62 IU (95% CI, 4.67-10.62) across 5 studies.

Conclusion: This meta-analysis provides robust evidence supporting the efficacy and safety of IV TCZ in patients with GO who are resistant to glucocorticoid therapy. The results highlight TCZ's comparable efficacy to glucocorticoids and suggest that TCZ could significantly expand clinical management options for GO. In the future, more high-quality, large-scale randomized controlled trials are still needed to confirm these findings.

Keywords: CAS; Graves’ ophthalmopathy; diplopia; proptosis; tocilizumab.