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. CONCLUSION 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.

中文翻译：

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Teprotumumab 对病程长、疾病活动度低的甲状腺眼病患者的疗效和安全性。

背景 早期炎症性甲状腺眼病 (TED) 可导致有症状的慢性疾病，包括失能性突眼。Teprotumumab 是一种 IGF-1 受体抑制剂，之前在急性高炎症 TED 试验中证明了疗效。目的 我们提供第一个在慢性/低疾病活动度 TED 中使用 teprotumumab 进行安慰剂对照试验的数据。设计 这是一项随机双盲、安慰剂对照试验。背景 这项研究在美国 11 个中心进行。参与者 TED 持续时间为 2-10 年、临床活动评分 (CAS) ≤ 1 或无额外炎症或眼球突出/复视进展≥1 年、距 TED 之前/距正常、甲状腺功能正常/轻度甲状腺功能减退/甲状腺功能亢进 ≥3 毫米，既往未使用 teprotumumab，且基线后 3 周内未使用类固醇。干预 患者每 3 周接受一次 (2:1) 静脉注射 teprotumumab 或安慰剂（总共 8 次输注）。主要观察指标 主要终点是第 24 周时眼球突出（毫米）的改善。评估不良事件（AE）。结果 42 名 teprotumumab 患者和 20 名安慰剂患者被随机分组​​。第 24 周时，teprotumumab 组的平均 (SD) 眼球突出改善 (-2.41 [0.228]) 高于安慰剂 (-0.92 [0.323])，差异 -1.48，95% CI -2.28，-0.69，P = 0.0004。各组之间发生 AE 的患者比例相似。替普妥尤单抗组和安慰剂组分别有 6 例（15%）和 2 例（10%）报告出现高血糖，9 例（22%）和 2 例（10%）出现听力障碍。AE 导致一名 teprotumumab（左耳传导性听力损失伴先天性异常）和一名安慰剂患者（输注相关）停药。没有死亡。结论 与安慰剂相比，Teprotumumab 在长期/低炎症 TED 中显着改善了眼球突出，证明了其功效，无论疾病持续时间/活动如何。安全性与之前报道的相当。