Comprehensive Comparisons of Different Treatments for Active Graves’ Orbitopathy: A Systematic Review and Bayesian Model-Based Network Meta-Analysis

Abstract Objective This study aims to assess the efficacy and safety of various treatments for active thyroid eye disease. Method We conducted a comprehensive search for randomized controlled trials (RCTs), and ongoing RCTs registered on Controlled Trials, targeting treatments for thyroid eye disease up until November 20, 2024. Employing a Bayesian framework, this network meta-analysis calculated risk ratios (RRs) or mean differences (MDs) with 95% confidence intervals (CIs) to size the effects for the predetermined outcomes. The study is registered with PROSPERO (CRD42024548030). Outcome The primary outcomes evaluated were overall response rate, clinical activity score(CAS), proptosis, diplopia and adverse events. Results For the overall response rate, teprotumumab (RR 5.5, 95%CI 2.3 to 16), mycophenolate combined intravenous glucocorticosteroids (IVGCs) demonstrated effectiveness over no treatment, ranked from most to least effective. Notably, teprotumumab showed the highest efficacy in reducing CAS (MD -1.57, 95%CI -3.81 to 0.68) and proptosis (MD -2.29, 95%CI -2.73 to -1.86). For diplopia improvement, teprotumumab and IVGCs were effective compared to no treatment. Conclusion Teprotumumab emerges as potentially the most effective treatment for reducing inflammation and increasing overall response rates when compared to no treatment, oral mycophenolate combined with intravenous glucocorticosteroids appears to be the best one in improving proptosis. While some treatments raise safety concerns due to reported adverse events, oral methotrexate combined with intravenous glucocorticosteroids appear to offer a favorable balance between efficacy and safety among the evaluated treatments.