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特普西单抗改善非对称性甲状腺眼病。

Improvement of asymmetric thyroid eye disease with teprotumumab.

机构信息

Orbital and Ophthalmic Plastic Surgery, Jules Stein Eye Institute, Los Angeles, California, USA

Oculoplastics, Cedars-Sinai Medical Center, Los Angeles, California, USA.

出版信息

Br J Ophthalmol. 2022 Jun;106(6):755-759. doi: 10.1136/bjophthalmol-2020-318314. Epub 2021 Feb 12.

Abstract

PURPOSE

Teprotumumab, a specific blocking antibody to the insulin like growth factor 1 receptor, significantly reduced proptosis in patients with thyroid eye disease (TED) in recent clinical trials. Given its specificity, we expect it to demonstrate greater efficacy on the worse affected orbit, in patients with asymmetric TED. Herein, we investigate the differential impact of teprotumumab on the orbits of such patients.

METHODS

In this pooled analysis of patients who were enrolled in the recent phase 2 (NCT01868997) and phase 3 (NCT03298867) trials, all patients with asymmetric TED (difference in exophthalmometry of ≥3 mm) were screened for eligibility. The primary outcomes of the trials, proptosis, diplopia and Clinical Activity Score (CAS) response, were evaluated in both orbits of patients who had received treatment or placebo, to examine the differential response from baseline to week 24.

RESULTS

From a pooled group of 84 patients randomised to receive teprotumumab and 87 randomised to placebo, 10 (12%) and 12 (14%), respectively, met the inclusion criteria. The teprotumumab-treated patients demonstrated significant reductions in proptosis, CAS and diplopia in both orbits of each patient and this was not seen with placebo. The reduction in proptosis and CAS was significantly greater in the worse affected orbit, improving symmetry. In the placebo arm, while the mean CAS in the study eye reduced over time, proptosis and diplopia did not change in either orbit.

CONCLUSION

The findings in this study suggest the differential impact of teprotumumab on orbits that are clinically more affected by TED, suggesting that teprotumumab reduces asymmetry.

摘要

目的

特普罗鲁单抗是一种针对胰岛素样生长因子 1 受体的特异性阻断抗体,在最近的临床试验中显著降低了甲状腺眼病(TED)患者的眼球突出度。鉴于其特异性,我们期望它在患有不对称性 TED 的患者中,对病情更严重的眼眶表现出更大的疗效。在此,我们研究了特普罗鲁单抗对这些患者眼眶的不同影响。

方法

在最近的 2 期(NCT01868997)和 3 期(NCT03298867)临床试验中入组的患者中进行了此项汇总分析,筛选出所有患有不对称性 TED(眼球突出度差值≥3mm)的患者,以评估其纳入标准。评估了接受治疗或安慰剂的患者双眼的试验主要结局,即眼球突出度、复视和临床活动评分(CAS)反应,以检查从基线到第 24 周的差异反应。

结果

在随机接受特普罗鲁单抗治疗的 84 名患者和随机接受安慰剂治疗的 87 名患者中,分别有 10 名(12%)和 12 名(14%)符合纳入标准。特普罗鲁单抗治疗组患者的双侧眼球突出度、CAS 和复视均显著降低,而安慰剂组则未见这种情况。在病情更严重的眼眶中,特普罗鲁单抗治疗的眼球突出度和 CAS 降低更为显著,改善了眼眶的对称性。在安慰剂组中,虽然研究眼的平均 CAS 随时间推移而降低,但双侧眼眶的眼球突出度和复视均未发生变化。

结论

本研究的结果表明,特普罗鲁单抗对 TED 临床影响更严重的眼眶具有不同的影响,提示特普罗鲁单抗可减轻眼眶的不对称性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fba5/9132868/dc355fb8ec09/bjophthalmol-2020-318314f01.jpg

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