# Redefining evidence for teprotumumab in thyroid eye disease: an updated meta-analysis of efficacy and safety

## TL;DR

This study confirms that teprotumumab is effective in treating thyroid eye disease, significantly improving symptoms like eye bulging and quality of life, though it may cause side effects like high blood sugar and hearing issues.

## Contribution

The paper provides an updated meta-analysis consolidating the efficacy and safety of teprotumumab in thyroid eye disease through a comprehensive synthesis of randomized trials.

## Key findings

- Teprotumumab significantly improves proptosis, diplopia, disease activity, and quality of life in thyroid eye disease.
- Common side effects include hyperglycemia, muscle spasms, dry skin, and hearing impairment.
- The findings support teprotumumab as a pivotal treatment option with a balanced risk-benefit profile.

## Abstract

Thyroid eye disease (TED) is a sight-threatening autoimmune disorder with limited effective therapies. Teprotumumab, an insulin-like growth factor-1 receptor inhibitor, has emerged as a promising treatment. However, a comprehensive synthesis of its efficacy and safety across randomized trials remains limited.

A systematic review and meta-analysis of randomized controlled trials (RCTs) comparing teprotumumab with placebo in TED was conducted. Primary outcomes included proptosis response, overall response, change in proptosis, diplopia response, achievement of a Clinical Activity Score (CAS) ≤1, changes in Graves’ ophthalmopathy–specific quality-of-life questionnaire (GO-QOL) scores and safety outcomes. Pooled risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated using random-effects models.

Seven RCTs involving 438 participants were included. Teprotumumab significantly improved all efficacy outcomes: proptosis response (RR, 6.87; 95% CI, 3.32 to 14.24), overall response (RR, 7.82; 95% CI, 3.36 to 18.18), reduction in proptosis (MD, -2.46 mm; 95% CI, -2.96 to -1.96), diplopia response (RR, 1.85; 95% CI, 1.28 to 2.68), CAS ≤1 (RR, 3.39; 95% CI, 2.41 to 4.78) and increase in GO-QOL overall score (MD, 10.87; 95% CI, 9.91 to 11.83). Safety analysis indicated elevated risks of hyperglycemia (RR, 2.82; 95% CI, 1.08 to 7.37), muscle spasms (RR, 3.83; 95% CI, 1.97 to 7.43), dry skin (RR, 6.54; 95% CI, 1.52 to 28.09), and hearing impairment (RR, 3.74; 95% CI, 1.26 to 11.13).

Teprotumumab provides substantial, consistent benefits in improving proptosis, diplopia, disease activity and GO-QOL in TED. Clinicians should monitor for adverse events, particularly hyperglycemia and hearing impairment. These findings reinforce teprotumumab as a pivotal therapeutic option and support balanced risk-benefit evaluation.