Teprotumumab for the treatment of Thyroid eye disease.

IF 22 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Endocrine reviews Pub Date : 2024-06-05 DOI:10.1210/endrev/bnae018
Shoaib Ugradar, Emil Malkhasyan, Raymond S Douglas
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Abstract

Thyroid eye disease (TED) is the most common extra thyroidal manifestation of Graves' disease (GD). It may also present in those who are hypothyroid or euthyroid. The characteristic clinical manifestations of TED: chemosis, lid swelling, proptosis and diplopia are driven by a combination of inflammation and extracellular matrix modification. It has recently emerged that one of the major drivers of this molecular signature is the over-expression of the insulin like growth factor-1 receptor (IGF-1R) on key effector cells in TED pathogenesis. The overexpression of the IGF-1R is coupled with a dysregulation of the IGF-1R axis, which links other pathways that modulate inflammation, such as fibrosis and extracellular matrix organization, in patients with TED. This overexpression is also found to persist from the acute stage into the chronic phase. Teprotumumab, a fully human immunoglobulin (Ig) G1 monoclonal antibody that inhibits the IGF-1R, recently gained approval in the US for the treatment of TED. In phase 2 and phase 3 clinical studies, teprotumumab showed efficacy in reducing inflammation, proptosis, diplopia and burden on quality of life, in patients who were treated. Post introduction studies have confirmed the results of the phase 2 and phase 3 studies. Since 2020, over 5, 800 patients have been treated with teprotumumab and it appears to be well tolerated. The American Thyroid Association and the European Thyroid Association have recommended it as first line therapy for patients with moderate to severe TED, who display features of proptosis and diplopia.

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治疗甲状腺眼病的特普罗单抗。
甲状腺眼病(TED)是巴塞杜氏病(GD)最常见的甲状腺外表现。甲状腺功能减退或甲状腺功能亢进的患者也可能出现该病。TED的特征性临床表现:化脓、眼睑肿胀、突眼和复视,是由炎症和细胞外基质改变共同引起的。最近发现,这种分子特征的主要驱动因素之一是胰岛素样生长因子-1受体(IGF-1R)在TED发病机制中的关键效应细胞上过度表达。IGF-1R的过度表达与IGF-1R轴的失调有关,而IGF-1R轴与TED患者中调节纤维化和细胞外基质组织等炎症的其他通路有关。这种过度表达还会从急性期持续到慢性期。抑制 IGF-1R 的全人源免疫球蛋白 (Ig) G1 单克隆抗体泰普单抗最近在美国获批用于治疗 TED。在 2 期和 3 期临床研究中,特普鲁单抗在减轻接受治疗的患者的炎症、突眼、复视和生活质量负担方面显示出疗效。引进后的研究证实了 2 期和 3 期研究的结果。自 2020 年以来,已有 5,800 多名患者接受了替普鲁单抗的治疗,其耐受性良好。美国甲状腺协会和欧洲甲状腺协会已将其推荐为具有突眼和复视特征的中重度 TED 患者的一线疗法。
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来源期刊
Endocrine reviews
Endocrine reviews 医学-内分泌学与代谢
CiteScore
42.00
自引率
1.00%
发文量
29
期刊介绍: Endocrine Reviews, published bimonthly, features concise timely reviews updating key mechanistic and clinical concepts, alongside comprehensive, authoritative articles covering both experimental and clinical endocrinology themes. The journal considers topics informing clinical practice based on emerging and established evidence from clinical research. It also reviews advances in endocrine science stemming from studies in cell biology, immunology, pharmacology, genetics, molecular biology, neuroscience, reproductive medicine, and pediatric endocrinology.
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