Efficacy and Safety of Rituximab for the Treatment of Graves' Orbitopathy: A Meta-analysis of Randomized Controlled Trials.

STUDY OBJECTIVE: To investigate the efficacy and safety of rituximab in patients with Graves' orbitopathy (GO).

DESIGN: Systematic review and meta-analysis of four randomized controlled trials.

PATIENTS: A total of 293 patients with GO who received rituximab or control (either glucocorticoids, the established first-line therapy [three trials], or saline [one trial]).

MEASUREMENTS AND RESULTS: Relevant studies published before February 2018 were identified from the PubMed, EMBASE, Cochrane Library, and Scopus databases and the ClinicalTrials.gov registry. Individual effect sizes were standardized, and a meta-analysis was conducted to calculate the pooled effect size by using a random-effects model. Treatment efficacy was assessed by measuring the following outcomes: clinical activity score (CAS), sight visual acuity reduction (NOSPECS) score, proptosis, diplopia, changes in eye volume, quality of life, and adverse events. In the four included trials, 113 patients in the rituximab group and 108 patients in the control group were evaluated. Compared with the control group, CAS (weighted mean difference 0.57, 95% confidence interval 0.25-0.89) was significantly reduced at 24 weeks in the rituximab group. Compared with the control group, considerable proptosis reduction was also observed in the rituximab group; however, the difference was not significant. The proportion of adverse events in the rituximab group was not significantly higher than that in the glucocorticoid control group, but one of the included trials indicated that the rituximab group had more serious adverse events than the saline control group.

CONCLUSION: Rituximab is a relatively safe and viable treatment that is superior to glucocorticoids or saline for patients with moderate to severe GO. However, the incidence of serious adverse events was disparate among the included trials. Additional studies involving a larger sample size and investigating the optimal rituximab dosage, frequency, and method of administration are warranted.