Lo Jui-En, Freitag Suzanne K, Liu Catherine Y, Barbesino Giuseppe, Ma Kevin Sheng-Kai
Center for Global Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Internal Medicine, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio.
Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts.
Ophthalmology. 2025 May 19. doi: 10.1016/j.ophtha.2025.05.012.
The insulin-like growth factor-1 receptor inhibitor teprotumumab is effective for thyroid eye disease (TED), but there is limited evidence on its long-term safety. We studied the long-term cardiovascular, renal, infectious, and safety outcomes of teprotumumab compared with intravenous (IV) glucocorticoids (GCs), oral GCs, and conservative treatment in patients with TED.
Population-based cohort study.
Patients with TED who initiated teprotumumab, GCs, or conservative treatment between January 1, 2020, and December 1, 2024, from 80 health care organizations in the United States.
Propensity scores were used to match baseline covariates including demographics, comorbidities, laboratory data, and medications. Cox proportional hazards models were used to calculate hazard ratios (HRs).
Outcomes included all-cause mortality and the risks of new-onset cardiovascular diseases, renal diseases, infectious outcomes, and safety outcomes, including hearing loss, within 5 years after initiating treatments.
Teprotumumab was associated with markedly lower all-cause mortality (teprotumumab vs IV GCs: HR 0.32, 95% CI 0.16-0.65; teprotumumab vs oral GCs: HR 0.20, 95% CI 0.10-0.39) and reduced risks of acute myocardial infarction (teprotumumab vs IV GCs: HR 0.37, 95% CI 0.15-0.95; teprotumumab vs oral GCs: HR 0.33, 95% CI 0.12-0.91), acute kidney failure (teprotumumab vs IV GCs: HR 0.54, 95% CI 0.31-0.94; teprotumumab vs oral GCs: HR 0.37, 95% CI 0.22-0.63), emergency department visits (teprotumumab vs IV GCs: HR 0.48, 95% CI 0.38-0.60; teprotumumab vs oral GCs: HR 0.60, 95% CI 0.48-0.75), hospitalizations (teprotumumab vs IV GCs: HR 0.31, 95% CI 0.23-0.40; teprotumumab vs oral GCs: HR 0.34, 95% CI 0.26-0.45), urinary tract infection (teprotumumab vs IV GCs: HR 0.60, 95% CI 0.41-0.89; teprotumumab vs oral GCs: HR 0.58, 95% CI 0.40-0.86), pneumonia (teprotumumab vs IV GCs: HR 0.37, 95% CI 0.22-0.61; teprotumumab vs oral GCs: HR 0.33, 95% CI 0.20-0.53), and severe sepsis (teprotumumab vs IV GCs: HR 0.24, 95% CI 0.10-0.64; teprotumumab vs oral GCs: HR 0.31, 95% CI 0.11-0.84). There was no difference in the risks of diabetes, chronic kidney disease, or inflammatory bowel disease, or complications requiring a hearing device, whereas there was a higher risk of hearing loss after starting teprotumumab compared with GCs (teprotumumab vs IV GCs: HR 2.43, 95% CI 1.67-3.55; teprotumumab vs oral GCs: HR 2.38, 95% CI 1.65-3.44). All-cause mortality was also markedly reduced in teprotumumab-treated patients when compared with patients receiving conservative treatment (HR 0.24, 95% CI 0.13-0.45).
Treatment with teprotumumab compared with IV or oral GCs was associated with reduced risks of death and cardiovascular, renal, and infectious outcomes in patients with TED. Teprotumumab may result in fewer adverse outcomes than systemic GCs for treating TED.
FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
胰岛素样生长因子-1受体抑制剂替普罗单抗对甲状腺眼病（TED）有效，但关于其长期安全性的证据有限。我们研究了替普罗单抗与静脉注射（IV）糖皮质激素（GCs）、口服GCs及保守治疗相比，在TED患者中的长期心血管、肾脏、感染及安全性结局。
基于人群的队列研究。
2020年1月1日至2024年12月1日期间，来自美国80个医疗机构，开始使用替普罗单抗、GCs或接受保守治疗的TED患者。
采用倾向评分匹配基线协变量，包括人口统计学、合并症、实验室数据和药物治疗情况。使用Cox比例风险模型计算风险比（HRs）。
结局包括全因死亡率以及开始治疗后5年内新发心血管疾病、肾脏疾病、感染性结局和安全性结局（包括听力丧失）的风险。
替普罗单抗与显著更低的全因死亡率相关（替普罗单抗与IV GCs相比：HR 0.32，95%CI 0.16 - 0.65；替普罗单抗与口服GCs相比：HR 0.20，95%CI 0.10 - 0.39），并降低了急性心肌梗死（替普罗单抗与IV GCs相比：HR 0.37，95%CI 0.15 - 0.95；替普罗单抗与口服GCs相比：HR 0.33，95%CI 0.12 - 0.91）、急性肾衰竭（替普罗单抗与IV GCs相比：HR 0.54，95%CI 0.31 - 0.94；替普罗单抗与口服GCs相比：HR 0.37，95%CI 0.22 - 0.63）、急诊就诊（替普罗单抗与IV GCs相比：HR 0.48，95%CI 0.38 - 0.60；替普罗单抗与口服GCs相比：HR 0.60，95%CI 0.48 - 0.75）、住院（替普罗单抗与IV GCs相比：HR 0.31，95%CI 0.23 - 0.40；替普罗单抗与口服GCs相比：HR 0.34，95%CI 0.26 - 0.45）、尿路感染（替普罗单抗与IV GCs相比：HR 0.60，95%CI 0.41 - 0.89；替普罗单抗与口服GCs相比：HR 0.58，95%CI 0.40 - 0.86）、肺炎（替普罗单抗与IV GCs相比：HR 0.37，95%CI 0.22 - 0.61；替普罗单抗与口服GCs相比：HR 0.33，95%CI 0.20 - 0.53）和严重脓毒症（替普罗单抗与IV GCs相比：HR 0.24，95%CI 0.10 - 0.64；替普罗单抗与口服GCs相比：HR 0.31，95%CI 0.11 - 0.84）的风险。糖尿病、慢性肾脏病或炎症性肠病的风险，或需要听力辅助设备的并发症方面无差异，而与GCs相比，开始使用替普罗单抗后听力丧失风险更高（替普罗单抗与IV GCs相比：HR 2.43，95%CI 1.67 - 3.55；替普罗单抗与口服GCs相比：HR 2.38，95%CI 1.65 - 3.44）。与接受保守治疗的患者相比，替普罗单抗治疗的患者全因死亡率也显著降低（HR 0.24，95%CI 0.13 - 0.45）。
与IV或口服GCs相比，替普罗单抗治疗可降低TED患者的死亡风险以及心血管、肾脏和感染性结局的风险。在治疗TED方面，替普罗单抗可能比全身使用GCs导致的不良结局更少。
专有或商业披露信息可在参考文献之后找到。
