Efficacy and Safety of Teprotumumab in Patients With Thyroid Eye Disease of Long Duration and Low Disease Activity

Raymond S. Douglas, Steven Couch, Sara T. Wester, Brian T. Fowler, Catherine Y. Liu, Prem S. Subramanian, Rosa Tang, Quang T. Nguyen, Robi N. Maamari, Shoaib Ugradar, Kate Hsu, Michael Karon, Marius N. Stan

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Context: Early inflammatory thyroid eye disease (TED) can lead to symptomatic chronic disease, including disabling proptosis. Teprotumumab, an insulin-like growth factor-1 receptor (IGF-1R) inhibitor, previously demonstrated efficacy in acute, high-inflammation TED trials. Objective: We present data from the first placebo-controlled trial with teprotumumab in chronic/low disease activity TED. Methods: This randomized double-masked, placebo-controlled trial, conducted at 11 US centers, enrolled adult participants with TED duration of 2 to 10 years, Clinical Activity Score (CAS) ≤ 1 or no additional inflammation or progression in proptosis/diplopia for ≥1 year, proptosis ≥3 mm from before TED and/or from normal, euthyroid/mildly hypo/hyperthyroid, no prior teprotumumab, and no steroids within 3 weeks of baseline. Patients received (2:1) intravenous teprotumumab or placebo once every 3 weeks (total 8 infusions). The primary endpoint was proptosis (mm) improvement at Week 24. Adverse events (AEs) were assessed. Results: A total of 62 (42 teprotumumab and 20 placebo) patients were randomized. At Week 24, least squares mean (SE) proptosis improvement was greater with teprotumumab (-2.41 [0.228]) than with placebo (-0.92 [0.323]), difference -1.48 (95% CI -2.28, -0.69; P = .0004). Proportions of patients with AEs were similar between groups. Hyperglycemia was reported in 6 (15%) vs 2 (10%) and hearing impairment in 9 (22%) vs 2 (10%) with teprotumumab and placebo, respectively. AEs led to discontinuation in 1 teprotumumab (left ear conductive hearing loss with congenital anomaly) and 1 placebo patient (infusion-related). There were no deaths. Conclusion: Teprotumumab significantly improved proptosis vs placebo in longstanding/low inflammation TED, demonstrating efficacy regardless of disease duration/activity. The safety profile was comparable to that previously reported.

Original languageEnglish
Pages (from-to)25-35
Number of pages11
JournalJournal of Clinical Endocrinology and Metabolism
Issue number1
StatePublished - Jan 1 2024


  • Graves disease
  • chronic
  • inactive
  • teprotumumab
  • thyroid eye disease


Dive into the research topics of 'Efficacy and Safety of Teprotumumab in Patients With Thyroid Eye Disease of Long Duration and Low Disease Activity'. Together they form a unique fingerprint.

Cite this