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teprotumumab治疗活动性甲状腺眼病
Teprotumumab for the Treatment of Active Thyroid Eye Disease


Raymond S. Douglas ... 其他 • 2020.01.23

摘要


背景

甲状腺眼病是一种使人衰弱、损害外貌并可能致盲的眼周疾病,且目前尚无获得美国食品和药品监督管理局(FDA)批准的药物疗法。强有力的证据表明,胰岛素样生长因子Ⅰ受体(IGF-ⅠR)与甲状腺眼病的发病机制相关。

 

方法

在一项随机、双盲、安慰剂对照、3期多中心试验中,我们以1∶1的比例将活动性甲状腺眼病患者分组,分别每3周1次静脉输入IGF-IR抑制剂teprotumumab(首次输入的剂量为10 mg/kg,之后的剂量为20 mg/kg)或安慰剂,治疗共持续21周;本分析的最后一次试验访视安排在第24周。主要结局是第24周时,在眼球突出方面有应答(眼球突出减少≥2 mm)。第24周时的预设次要结局包括总体应答(临床活动度评分[Clinical Activity Score]降低≥2分且眼球突出减少≥2 mm)、临床活动度评分为0分或1分(表示无炎症或有轻微炎症)、眼球突出情况在试验访视期间(从基线至第24周)的平均变化、在复视方面有应答(复视减轻≥1级)以及格雷夫斯眼病特异性生活质量(Graves' ophthalmopathy-specific quality-of-life,GO-QOL)问卷总分在试验访视期间(从基线至第24周)的平均变化(平均变化≥6分被视为有临床意义)。

 

结果

共计41例患者被分配至teprotumumab组,42例被分配至安慰剂组。第24周时,teprotumumab组中在眼球突出方面有应答的患者百分比高于安慰剂组(83% [34例患者] vs. 10% [4例患者],P<0.001),要使1例患者在眼球突出方面有应答,需要治疗的患者人数为1.36。teprotumumab组的所有次要结局均显著优于安慰剂组,包括总体应答(78%的患者[32] vs. 7% [3]),临床活动度评分为0分或1分(59% [24] vs. 21% [9])、眼球突出情况的平均变化(-2.82 mm vs. -0.54 mm)、在复视方面有应答(68% [19/28] vs. 29% [8/28])以及GO-QOL总分的平均变化(13.79分vs. 4.43分)(对于所有结局,P≤0.001)。在接受眼眶影像学检查的teprotumumab组6例患者中,我们观察到眼外肌缩小或眼眶脂肪量减少,或者同时观察到这两者。大多数不良事件的严重程度为轻度或中度;teprotumumab组发生了2起严重事件,其中1起(输液反应)导致患者终止治疗。

 

结论

在活动性甲状腺眼病患者中,与安慰剂相比,teprotumumab在眼球突出、临床活动度评分、复视和生活质量方面使患者获得了较好结局;严重不良事件不常见(由Horizon Therapeutics资助;OPTIC在ClinicalTrials.gov注册号为NCT03298867,在EudraCT注册号为2017-002763-18)。





作者信息

Raymond S. Douglas, M.D., Ph.D., George J. Kahaly, M.D., Ph.D., Amy Patel, M.D., Saba Sile, M.D., Elizabeth H.Z. Thompson, Ph.D., Renee Perdok, M.S., James C. Fleming, M.D., Brian T. Fowler, M.D., Claudio Marcocci, M.D., Michele Marinò, M.D., Alessandro Antonelli, M.D., Roger Dailey, M.D., Gerald J. Harris, M.D., Anja Eckstein, M.D., Jade Schiffman, M.D., Rosa Tang, M.D., Christine Nelson, M.D., Mario Salvi, M.D., Sara Wester, M.D., Jeffrey W. Sherman, M.D., Thomas Vescio, M.D., Robert J. Holt, Pharm.D., and Terry J. Smith, M.D.
From Cedars–Sinai Medical Center, Los Angeles (R.S.D., A.P.); Johannes Gutenberg University Medical Center, Mainz (G.J.K.), and University Hospital Essen, Essen (A.E.) — both in Germany; Horizon Therapeutics, Lake Forest, IL (S.S., E.H.Z.T., R.P., J.W.S., T.V., R.J.H.); University of Tennessee Health Science Center, Memphis (J.C.F., B.T.F.); University of Pisa, Pisa (C.M., M.M., A.A.), and Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan (M.S.) — both in Italy; Oregon Health and Sciences University, Portland (R.D.); Medical College of Wisconsin Eye Institute, Milwaukee (G.J.H.); Eye Wellness Center–Neuro-Eye Clinical Trials, Houston (J.S., R.T.); Kellogg Eye Center–Michigan Medicine (C.N., T.J.S.) and University of Michigan Medical School (T.J.S.) — both in Ann Arbor; and Bascom Palmer Eye Institute, Miami (S.W.). Address reprint requests to Dr. Douglas at Cedars–Sinai Medical Center, W. Medical Office Towers, 8635 W. Third St., Suite 650W, Los Angeles, CA 90048, or at raymond.douglas@cshs.org.

 

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