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

Abstract Context Graves orbitopathy is a specialized immunoinflammatory disorder related to abnormal thyroid function. Due to the complexity of the disease and its propensity to reoccur, targeted treatment is essential to improve the symptoms. Objective This study aims to assess the efficacy and safety of various treatments for active thyroid eye disease. Methods We conducted a comprehensive search for randomized controlled trials (RCTs), and ongoing RCTs registered on Controlled Trials, targeting treatments for thyroid eye disease until November 20, 2024. Employing a Bayesian framework, this network meta-analysis calculated risk ratios (RRs) or mean differences (MDs) with 95% 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 with no treatment. Conclusion Teprotumumab emerges as potentially the most effective treatment for reducing inflammation and increasing overall response rates when compared with no treatment; oral mycophenolate combined with IVGCs appears to be the best for improving proptosis. While some treatments raise safety concerns due to reported adverse events, oral methotrexate combined with IVGCs appear to offer a favorable balance between efficacy and safety among the evaluated treatments.