Teprotumumab for Thyroid Eye Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Real-World Studies.

Abstract

Topic: Teprotumumab is the first FDA-approved biologic for moderate-to-severe thyroid eye disease (TED). Although efficacy has been established in randomized controlled trials (RCTs), real-world studies (RWS) have reported different efficacy and safety patterns, supporting an updated synthesis.

Clinical relevance: A comprehensive assessment of teprotumumab across trials and routine clinical practice is needed to guide treatment decisions.

Methods: This systematic review and meta-analysis included RCTs and RWS evaluating intravenous teprotumumab in adults with TED and reporting at least one prespecified efficacy or safety outcome. Other anti-IGF-1R RCTs were used only in supplementary class analyses. PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to August 10, 2026. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Cochrane RoB 2 tool and Joanna Briggs Institute criteria. Fixed- or random-effects models were selected according to heterogeneity. Risk ratios were used for dichotomous outcomes, mean differences for continuous outcomes, and proportions for single-arm RWS. Certainty was evaluated using GRADE. The protocol was registered in PROSPERO (CRD420251152338).

Results: Thirty-six studies (6 RCTs and 30 RWS) were included; 4 RCTs evaluated teprotumumab and 2 evaluated other anti-IGF-1R antibodies. Proptosis response favored teprotumumab in RCTs (risk ratio, 4.55; 95% confidence interval, 2.52-8.23) and was achieved by 82% of patients in RWS (95% confidence interval, 0.78-0.86; 11 studies, 482 patients). Diplopia response also favored teprotumumab in RCTs (risk ratio, 2.13; 95% confidence interval, 1.51-2.98), while 60% of patients improved in RWS (95% confidence interval, 0.51-0.68; 6 studies, 204 patients). Hyperglycemia was more frequent with teprotumumab in RCTs (risk ratio, 2.67; 95% confidence interval, 1.04-6.85) and occurred in 17% of patients in RWS (13 studies, 671 patients). Hearing impairment was also increased in RCTs (risk ratio, 4.05; 95% confidence interval, 1.50-10.96) and occurred in 18% of patients in RWS (13 studies, 592 patients).

Conclusion: Teprotumumab improves proptosis and diplopia across study designs, but hyperglycemia and hearing impairment in real-world practice warrant appropriate patient selection and monitoring.