Purpose Various treatments have been investigated for Graves’ ophthalmopathy (GO). We aimed to provide an overall profile of the efficacy and tolerability of various interventions for active and moderate to severe GO.

Methods PubMed, Embase and the Cochrane Central Register of Controlled Trials were searched on 6 July 2018. Randomised controlled trials (RCT) investigating GO treatments were included. Two researchers independently extracted data according to a predefined form. A random effects network meta-analysis was performed using a frequentist approach. The primary outcome was efficacy, and the secondary outcome was tolerability (side effect discontinuation).

Results Thirty-three studies with 1846 patients with GO were included. Orbital radiotherapy (ORT) plus intravenous glucocorticoids (IVGC) (OR 27.11; 95% CI 4.57 to 160.92), mycophenolate mofetil (MMF) (24.40, 95% CI 5.28 to 112.67), oral glucocorticoids (OGC) plus ciclosporin (20.22, 95% CI 1.60 to 255.20), IVGC plus MMF (12.08, 95% CI 2.96 to 49.35), teprotumumab (8.92, 95% CI 2.51 to 31.77), ORT plus OGC (4.88, 95% CI 1.25 to 19.06), rituximab (RTX) (4.85, 95% CI 1.18 to 19.86), somatostatin analogues (4.23, 95% CI 1.60 to 11.16), OGC plus azathioprine (AzA) (5.77, 95% CI 1.17 to 28.47) and IVGC (4.96, 95% CI 1.96 to 12.55) showed significantly better improvement than no treatment. ORT plus IVGC ranked first, followed by MMF. High heterogeneity and significant local inconsistency were observed in the RTX studies. The results of the sensitivity analyses were similar to those of the main analysis.

Conclusion A robust recommendation regarding the best treatment cannot be made, because most evidence was rated as low or very low quality according to the Grading of Recommendations, Assessment, Development and Evaluations framework. Large RCTs and individual participant data meta-analyses are necessary to confirm these results and explore potential moderators.

PROPERO trial registration number CRD42018103029.