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

Abstract

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.

Immune checkpoints: new insights into the pathogenesis of thyroid eye disease

“…Patients with TED often experience disfigurement, which brings a tremendous psychological burden to them. While the FDA has approved the use of teprotumumab in the treatment of TED, some patients may exhibit intolerance to this medication, experiencing adverse effects such as muscular spasms, nausea, and hearing impairment ( 47 , 48 , 116 , 117 ), and the high cost of teprotumumab also brings heavy economic burden to patients around the world. The identification of CD34 + fibrocytes and the presence of immune checkpoints have introduced novel concepts in the investigation of the underlying processes of TED.…”

A Prospective Study Examining Audiometry Outcomes Following Teprotumumab Treatment for Thyroid Eye Disease

“…In phases 2, 3, and 4 randomized double-masked clinical trials (RCTs), 1 , 2 teprotumumab was more effective than placebo in reducing proptosis, diplopia, and inflammation in patients with active TED. 1 , 3 Since its introduction, there have been a growing number of studies that have reported on hearing dysfunction after treatment with teprotumumab.…”