Department of Surgery (RSD, YW), Division of Ophthalmology, Cedars Sinai Medical Center, Los Angeles, California; State Key Laboratory of Ophthalmology (RSD), Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China; Department of Ophthalmology (RAD), Casey Eye Institute, Portland, Oregon; Department of Ophthalmology (GJH), Medical College of Wisconsin, Milwaukee, Wisconsin; Bascom Palmer Eye Institute (STW), University of Miami, Miami, Florida; Eye Wellness Center-Neuro-Eye Clinical Trials (JSS, RAT), Inc, Houston, Texas; Hamilton Eye Institute (BF, JF), University of Tennessee Health Science Center, Memphis, Tennessee; and Department of Ophthalmology and Visual Sciences (TJS), Kellogg Eye Center, and Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan.
J Neuroophthalmol. 2021 Dec 1;41(4):461-468. doi: 10.1097/WNO.0000000000001134.
Thyroid eye disease (TED) is a vision-threatening and debilitating condition that until very recently had no Food and Drug Administration (FDA)-approved medical therapies. Teprotumumab has recently been approved to treat TED. We aim to provide guidance for its use, based on the input of the US investigators who participated in Phase 2 and Phase 3 clinical trials.
An expert panel was convened on October 11th and November 16th of 2019. All panel members had extensive experience as investigators in the Phase 2 and/or Phase 3 clinical trials of teprotumumab. Consensus among those investigators was reached to determine patient characteristics most appropriate for teprotumumab treatment. Safety guidelines were also reviewed and agreed on.
The authors recommend that teprotumumab be considered first-line therapy for patients with clinically significant ophthalmopathy, including those with disease duration exceeding 9 months. The clinical activity score (CAS) may be useful for longitudinal monitoring but should not be used to determine treatment eligibility. Criteria will likely be expanded after more experience with the drug. Using teprotumumab for patients with TED with substantial signs, symptoms, or morbidity without a CAS score of >4 (e.g., progressive proptosis, diplopia, and early compressive optic neuropathy) or more, could be considered. Diabetes mellitus and inflammatory bowel disease comorbidities should not be exclusionary, but stringent monitoring in these patients is recommended. Drug dosing, administration interval, and duration should adhere to the study protocol: 8 infusions, separated by 3 weeks. Patients with more severe disease may benefit from additional doses. Corticosteroids can be used before or during teprotumumab therapy. Clinical and laboratory monitoring should be consistent with good clinical practice for patients receiving teprotumumab.
Confirming the efficacy of teprotumumab usage outside the narrow parameters of the completed clinical trials will require rigorous scientific validation. As a step in that direction, we believe its on-label usage is appropriately applied to all patients with TED with substantial symptoms or morbidity, as judged by their physician.
甲状腺眼病（TED）是一种威胁视力且使人虚弱的疾病，直到最近才没有获得美国食品和药物管理局（FDA）批准的医疗疗法。特普罗斯单抗最近已被批准用于治疗 TED。我们旨在根据参与 2 期和 3 期临床试验的美国研究人员的意见，为其使用提供指导。
于 2019 年 10 月 11 日和 11 月 16 日召集了一个专家小组。所有小组成员均在特普罗斯单抗的 2 期和/或 3 期临床试验中具有丰富的研究经验。研究人员达成共识，确定最适合特普罗斯单抗治疗的患者特征。还审查并同意了安全指南。
作者建议将特普罗斯单抗作为具有临床意义的眼病患者的一线治疗药物，包括疾病持续时间超过 9 个月的患者。临床活动评分（CAS）可能对纵向监测有用，但不应用于确定治疗资格。在获得更多药物经验后，标准可能会扩大。对于 CAS 评分>4（例如，进行性眼球突出、复视和早期压迫性视神经病变）或更高、且有 TED 显著体征、症状或发病率的患者，可以考虑使用特普罗斯单抗。糖尿病和炎症性肠病合并症不应排除，但建议对这些患者进行严格监测。药物剂量、给药间隔和持续时间应遵守研究方案：8 次输注，间隔 3 周。病情更严重的患者可能受益于额外的剂量。在特普罗斯单抗治疗前或治疗期间可以使用皮质类固醇。接受特普罗斯单抗治疗的患者的临床和实验室监测应符合良好的临床实践。
在完成临床试验的狭窄参数之外确认特普罗斯单抗使用的疗效需要严格的科学验证。作为朝这个方向迈出的一步，我们认为，根据医生的判断，所有有大量症状或发病率的 TED 患者均适用该药的标签内使用。
