Wirksamkeit von Teprotumumab bei der chronischen endokrinen Orbitopathie

Abstract

Context: 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. Objective: We present data from the first placebo-controlled trial with teprotumumab in chronic/low disease activity TED. Design: This was a randomized double-masked, placebo-controlled trial. Setting: The study was conducted in 11 US centers. Participants: 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. Intervention: Patients received (2:1) intravenous teprotumumab or placebo once every 3 weeks (total 8 infusions). Main outcome measures: The primary endpoint was proptosis (millimeter) improvement at Week-24. Adverse events (AEs) were assessed. Results: 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.