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Early inflammatory thyroid eye disease (TED) can lead to symptomatic chronic disease including disabling proptosis. Teprotumumab, an IGF-1 receptor inhibitor, previously demonstrated efficacy in acute, high-inflammation TED trials.
We present data from the first placebo-controlled trial with teprotumumab in chronic/low disease activity TED.
This was a randomized double-masked, placebo-controlled trial.
The study was conducted in 11 US centers.
Adults with TED duration 2-10 years, Clinical Activity Score (CAS) ≤ 1 or no additional inflammation or progression in proptosis/diplopia for ≥1 year, proptosis ≥3 mm from before TED/from normal, euthyroid/mildly hypo/hyperthyroid, no prior teprotumumab, and no steroids within 3 weeks of baseline participated.
Patients received (2:1) intravenous teprotumumab or placebo once every 3 weeks (total 8 infusions).
The primary endpoint was proptosis (millimeter) improvement at Week-24. Adverse events (AEs) were assessed.
42 teprotumumab and 20 placebo patients were randomized. At Week-24, mean (SD) proptosis improvement was greater with teprotumumab (-2.41 [0.228]) than 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 one teprotumumab (left ear conductive hearing loss with congenital anomaly) and one placebo patient (infusion-related). There were no deaths.
Teprotumumab significantly improved proptosis versus placebo in longstanding/low inflammation TED, demonstrating its efficacy regardless of disease duration/activity. The safety profile was comparable to that previously reported.
© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.