Efficacy and Safety of Teprotumumab in Thyroid Eye Disease: A Systematic Review and Meta-Analysis.

Summary

Across 4 RCTs (n=210 teprotumumab; n=193 controls) and 6 observational studies, teprotumumab significantly improved proptosis response, diplopia, and CAS versus placebo, with a large reduction in proptosis. Adverse events and serious adverse events were more frequent with teprotumumab, underscoring the need for careful monitoring and risk-benefit discussions.

Key Findings

• In RCTs (n=210 teprotumumab; n=193 controls), teprotumumab improved proptosis response (RR 4.18), diplopia regression (RR 2.29), and CAS (RR 3.09) versus placebo.
• Marked reduction in proptosis was observed (standardized mean difference −8.38).
• Adverse events and serious adverse events were more frequent with teprotumumab; observational studies showed AE incidence ~0.78 and serious AEs ~0.31.

Clinical Implications

Teprotumumab can be considered a first-line option for active moderate-to-severe TED, with counseling on AEs (e.g., hyperglycemia, hearing changes) and structured monitoring; shared decision-making is essential, especially in patients with comorbid diabetes or otologic risk.

Limitations

• Heterogeneity in prior treatments, disease activity, and dosing schedules across included studies
• Safety follow-up durations are limited; long-term relapse and AE trajectories remain uncertain

Future Directions

Long-term safety/effectiveness registries, head-to-head trials versus other immunomodulators, and strategies to mitigate AEs (e.g., metabolic monitoring protocols).