Abstract
Background: Long-duration thyroid eye disease (TED) may present with persistent proptosis despite the absence of inflammatory symptoms, and treatment options have been limited to surgical intervention. Recently, teprotumumab, a monoclonal antibody, has garnered interest as a non-surgical option to reduce proptosis in such cases. This systematic review investigates the impact of teprotumumab on reducing proptosis in long-duration TED. Methods: A search was conducted across major online databases, and data were aggregated from observational studies, clinical trials and case series. Nine studies met the inclusion criteria. Cumulative and weighted effect measures were synthesized. The biases and limitations of each study were assessed. Results: Existing evidence shows teprotumumab to be highly efficacious in reducing proptosis in chronic TED; however, there are significant limitations in the quality of existing evidence. The cumulative meta-analysis reveals a mean proptosis reduction of 3.05 ± 0.54 mm across 182 orbits from nine studies, and the weighted meta-analysis shows a mean reduction of 2.69 ± 0.53 mm across 172 orbits from eight studies. Discussion: While existing clinical studies are open to bias and intrinsically limited, the meta-analysis dilutes the risk of bias by weighting more precise evidence, providing the highest quality evidence to date. Further research is essential to understand teprotumumab's long-term efficacy and comparative advantages over surgical options. These findings have significant implications for treating persistent proptosis in patients with long-duration TED, potentially offering a non-surgical alternative where options were previously limited.