Center for Health Outcomes and PharmacoEconomic Research, University of Arizona, Tucson, AZ, USA.
Drug sector, Saudi Food and Drug Authority, Riyadh, Saudi Arabia.
Expert Opin Drug Saf. 2021 Apr;20(4):489-497. doi: 10.1080/14740338.2021.1877272. Epub 2021 Jan 25.
The risk of immune-related(ir)-hypothyroidism in older patients with advanced melanoma treated with anti-CTLA4 or anti-PD1 therapies is poorly understood, especially in the real-world setting. We identified older patients (≥65 years) diagnosed with advanced melanoma between 2011-2015 and treated with anti-CTLA4 or anti-PD1 agents in the SEER-Medicare database. Applying probability-of-treatment-weighting for confounder adjustment and proportional hazards models, we estimated the risk of ir-hypothyroidism between treatment initiation and up to 90 days from last dose between anti-PD1 and anti-CTLA4 users. Of 210 older patients with advanced melanoma identified, 164 received anti-CTLA4 (ipilimumab) and 46 anti-PD1 agents (11 nivolumab, 35 pembrolizumab). There was no statistically significant difference in ir-hypothyroidism risk between anti-PD1 and anti-CTLA4 users (HR=2.15, 95%CI=0.83-5.53). Pairwise medication comparisons showed a lower risk among ipilimumab versus nivolumab (HR=0.15, 95%CI=0.06-0.40) and pembrolizumab versus nivolumab users (HR=0.13, 95%CI=0.03-0.55). Sensitivity analyses using an all-stages melanoma cohort did not show a difference in ir-hypothyroidism risk between medication classes and individual medications.This retrospective claims data analysis revealed no statistically significant difference in ir-hypothyroidism risk between anti-CTLA4 or anti-PD1 users. However, patients with advanced melanoma treated with ipilimumab or pembrolizumab may have a lower ir-hypothyroidism risk compared to nivolumab users.
在接受抗 CTLA4 或抗 PD1 治疗的老年晚期黑色素瘤患者中，免疫相关（ir）-甲状腺功能减退症的风险尚不清楚，尤其是在真实世界环境中。我们在 SEER-Medicare 数据库中确定了 2011-2015 年间被诊断为晚期黑色素瘤且接受抗 CTLA4 或抗 PD1 药物治疗的老年患者（≥65 岁）。通过治疗权重法进行混杂因素调整和比例风险模型，我们在抗 PD1 和抗 CTLA4 使用者之间，从治疗开始到最后一剂药物后 90 天内，估计了 ir-甲状腺功能减退症的风险。在 210 名被确定为晚期黑色素瘤的老年患者中，164 名接受了抗 CTLA4（伊匹单抗）治疗，46 名接受了抗 PD1 药物治疗（11 名纳武单抗，35 名派姆单抗）。抗 PD1 和抗 CTLA4 使用者之间的 ir-甲状腺功能减退症风险无统计学显著差异（HR=2.15，95%CI=0.83-5.53）。药物间比较显示，伊匹单抗与纳武单抗（HR=0.15，95%CI=0.06-0.40）和派姆单抗与纳武单抗使用者（HR=0.13，95%CI=0.03-0.55）的风险较低。使用所有阶段黑色素瘤队列的敏感性分析并未显示药物类别和个别药物之间的 ir-甲状腺功能减退症风险存在差异。这项回顾性索赔数据分析显示，抗 CTLA4 或抗 PD1 使用者之间的 ir-甲状腺功能减退症风险无统计学显著差异。然而，与纳武单抗使用者相比，接受伊匹单抗或派姆单抗治疗的晚期黑色素瘤患者的 ir-甲状腺功能减退症风险可能较低。
