Purpose

To evaluate teprotumumab safety/efficacy in patients with thyroid eye disease (TED) who were nonresponsive or who experienced a disease flare.

Design

The Treatment of Graves’ Orbitopathy to Reduce Proptosis with Teprotumumab Infusions in an Open-Label Clinical Extension Study (OPTIC-X) is a teprotumumab treatment and re-treatment trial following the placebo-controlled teprotumumab Phase 3 Treatment of Graves’ Orbitopathy (Thyroid Eye Disease) to Reduce Proptosis with Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study (OPTIC) trial.

Participants

Patients who previously received placebo (n = 37) or teprotumumab (n = 14) in OPTIC.

Methods

OPTIC nonresponders or those who flared (≥2-mm increase in proptosis, ≥2-point increase in clinical activity score [CAS], or both) during follow-up were treated for the first time (previous placebo patients) or re-treated with teprotumumab in OPTIC-X with 8 infusions over 24 weeks.

Main Outcome Measures

Proptosis response and safety. Secondary outcomes included proptosis, CAS, subjective diplopia, and quality-of-life.

Results

Thirty-three of 37 placebo-treated OPTIC patients (89.2%) became proptosis responders (mean ± standard deviation, –3.5 ± 1.7 mm) when treated with teprotumumab in OPTIC-X. The responses were equivalent to the OPTIC study. In these responders, proptosis, CAS of 0 or 1, and diplopia responses were maintained in 29 of 32 patients (90.6%), 20 of 21 patients (95.2%), and 12 of 14 patients (85.7%), respectively, at follow-up week 48. The median TED duration was 12.9 months versus 6.3 months in those treated with teprotumumab in the OPTIC study. Of the 5 OPTIC teprotumumab nonresponders re-treated in OPTIC-X, 2 responded, 1 showed a proptosis reduction of 1.5 mm from OPTIC baseline, and 2 discontinued treatment early. Of the OPTIC teprotumumab responders who experienced flare, 5 of 8 patients (62.5%) responded when re-treated (mean proptosis reduction, 1.9 ± 1.2 mm from OPTIC-X baseline and 3.3 ± 0.7 mm from OPTIC baseline). Compared with published double-masked trials and their integrated follow-up, no new safety signals were identified. Mild hearing impairment was reported; 4 events occurred during the first course of treatment, and 2 events reoccurred after re-treatment.

Conclusions

Patients with TED of longer disease duration responded similarly to those treated earlier in the disease course. Patients with an insufficient initial response or flare may benefit from additional teprotumumab therapy. No new safety risk was identified; however additional postmarketing pharmacovigilance is ongoing.

中文翻译：

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Teprotumumab 在长期甲状腺眼病和再治疗中的疗效、安全性和持久性

目的

评估 teprotumumab 在无反应或疾病发作的甲状腺眼病 (TED) 患者中的安全性/有效性。

设计

在一项开放标签临床扩展研究 (OPTIC-X) 中使用 Teprotumumab 输注治疗 Graves 眼眶病以减少眼球突出是继安慰剂对照 teprotumumab 治疗 Graves 眼眶病（甲状腺眼）后的一项 teprotumumab 治疗和再治疗试验疾病）在随机、安慰剂对照、临床研究 (OPTIC) 试验中使用 Teprotumumab 输注减少眼球突出。

参与者

先前在 OPTIC 中接受安慰剂 (n = 37) 或 teprotumumab (n = 14) 的患者。

方法

OPTIC 无反应者或在随访期间突然发作（眼球突出增加 ≥ 2 毫米，临床活动评分 [CAS] 增加 ≥ 2 点，或两者兼有）的患者首次接受治疗（既往安慰剂患者）或再次治疗在 OPTIC-X 中使用 teprotumumab，在 24 周内进行 8 次输注。

主要观察指标

眼球突出反应和安全性。次要结局包括眼球突出、CAS、主观复视和生活质量。

结果

在 OPTIC-X 中接受 teprotumumab 治疗时，37 名接受安慰剂治疗的 OPTIC 患者中有 33 名 (89.2%) 成为眼球突出反应者（平均值 ± 标准差，–3.5 ± 1.7 mm）。反应等同于 OPTIC 研究。在这些反应者中，眼球突出、CAS 为 0 或 1 和复视反应分别在 32 名患者中的 29 名 (90.6%)、21 名患者中的 20 名 (95.2%) 和 14 名患者中的 12 名 (85.7%) 中维持。至第 48 周。在 OPTIC 研究中，使用 teprotumumab 治疗的患者的中位 TED 持续时间为 12.9 个月，而 6.3 个月。在 OPTIC-X 中重新治疗的 5 名 OPTIC teprotumumab 无反应者中，2 名有反应，1 名显示眼球突出比 OPTIC 基线减少 1.5 mm，2 名提前停止治疗。在经历耀斑的 OPTIC teprotumumab 反应者中，8 名患者中有 5 名（62.5%）在重新治疗时有反应（平均眼球突出减少，1. 距 OPTIC-X 基线 9 ± 1.2 mm，距 OPTIC 基线 3.3 ± 0.7 mm）。与已发表的双盲试验及其综合随访相比，未发现新的安全信号。报告有轻度听力障碍；首疗程发生4例，再治疗后再次发生2例。

结论

病程较长的 TED 患者的反应与病程早期治疗的患者相似。初始反应不足或突然发作的患者可能会受益于额外的 teprotumumab 治疗。未发现新的安全风险；然而，额外的上市后药物警戒正在进行中。