Department of Endocrinology, Walter Reed National Military Medical Center, Bethesda, Maryland; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
Department of Ophthalmology, Walter Reed National Military Medical Center, Bethesda, Maryland.
Endocr Pract. 2024 Nov;30(11):1038-1043. doi: 10.1016/j.eprac.2024.08.005. Epub 2024 Aug 24.
To evaluate the effects of teprotumumab on ophthalmologic and biochemical findings and assess potential genetic markers for response to treatment.
This is a retrospective study. Participants were 18-76 year old. All subjects were treated with teprotumumab. The primary outcome was the change in proptosis before and after teprotumumab treatment. Secondary outcomes include change in other ophthalmic measures and thyroid laboratory tests. Human leukocyte antigens (HLA) markers were analyzed for response to teprotumumab.
Twenty-six patients were included in the final analysis. There was a significant decrease in thyroid stimulating immunoglobulin and thyrotropin receptor antibody levels and significant increases in glycated hemoglobin A1c, fasting glucose, and total T3 levels. There was also significant reduction in proptosis, clinical activity score, retinal nerve fiber layer thickness, ganglion cell analysis, and intraocular pressure. HLA haplotypes were distinct between responders and nonresponders, with HLA-DRB3 02:02:01G, HLA-DRB4 neg, and HLA-DQB1 02:01:01G demonstrating better response to teprotumumab and HLA-A 23:01:01G strongly correlating to nonresponse.
Patients with both acute and chronic thyroid eye disease treated with teprotumumab had a significant reduction in thyroid stimulating immunoglobulin and thyrotropin receptor antibody levels and improvement in proptosis, clinical activity score, retinal nerve fiber layer and ganglion cell analysis thickness, and intraocular pressure. HLA may predict responders vs nonresponders. Further studies with longer duration and larger population comparing teprotumumab with steroids or other immunomodulatory agents (tocilizumab, rituximab, etc) may be helpful.
评估 teprotumumab 对眼科和生化指标的影响，并评估潜在的治疗反应遗传标志物。
这是一项回顾性研究。参与者为 18-76 岁。所有患者均接受 teprotumumab 治疗。主要结局是 teprotumumab 治疗前后眼球突出度的变化。次要结局包括其他眼科测量和甲状腺实验室检查的变化。分析人类白细胞抗原（HLA）标志物对 teprotumumab 的反应。
最终分析纳入 26 例患者。甲状腺刺激免疫球蛋白和促甲状腺素受体抗体水平显著下降，糖化血红蛋白 A1c、空腹血糖和总 T3 水平显著升高。眼球突出度、临床活动评分、视网膜神经纤维层厚度、神经节细胞分析和眼内压也显著降低。应答者和无应答者之间的 HLA 单倍型明显不同，HLA-DRB3 02:02:01G、HLA-DRB4 阴性和 HLA-DQB1 02:01:01G 对 teprotumumab 的反应更好，HLA-A 23:01:01G 与无反应性强烈相关。
接受 teprotumumab 治疗的急性和慢性甲状腺眼病患者，甲状腺刺激免疫球蛋白和促甲状腺素受体抗体水平显著降低，眼球突出度、临床活动评分、视网膜神经纤维层和神经节细胞分析厚度以及眼内压均有所改善。HLA 可能预测应答者与无应答者。进一步的研究需要更长的时间和更大的人群，比较 teprotumumab 与类固醇或其他免疫调节剂（托珠单抗、利妥昔单抗等）的疗效可能会有所帮助。
