Lindsay Alistair C, Walker Alexander M, Schneeweiss Sebastian
Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine Brigham and Women's Hospital, Harvard Medical School Boston MA.
Department of Epidemiology Harvard T.H. Chan School of Public Health Boston MA.
J Am Heart Assoc. 2025 Jan 7;14(1):e035689. doi: 10.1161/JAHA.124.035689. Epub 2024 Dec 24.
Immune checkpoint inhibitors have improved the clinical outcomes of several cancers but have also been associated with a greater risk of immune-related adverse effects, especially when combined. The objective of this study was to investigate the incidence of myocarditis in relation to the use of dual concurrent versus single immune checkpoint inhibitors therapies.
A cohort study was conducted using medical and pharmacy claims data (2011-2022) from a large US commercial insurer. Cox regression quantified the comparative risks of myocarditis or heart failure in patients with cancer receiving treatment with combination therapy (nivolumab and ipilimumab) in comparison to taking a single immune checkpoint inhibitor only. Mean follow-up time in 53 018 patients was 226 days (interquartile range, 93-495 days). There were 148 cases of myocarditis (0.3%), 33 (0.7%) in patients on combination therapy, and 115 (0.2%) in patients on monotherapy. The risk of myocarditis per 1000 patients was 7.40 in the combination therapy group and 2.37 in the monotherapy group (risk ratio, 3.12 [95% CI, 2.12-4.60]). Using multivariable regression analysis, the hazard ratio for myocarditis in the combination therapy group was 2.38 (1.57-3.63). No difference in the risk of heart failure was found between combination and single therapy.
Therapy with 2 immune checkpoint inhibitors was associated with an increased risk of myocarditis compared with monotherapy, with most cases occurring in the first 6 months of therapy.
免疫检查点抑制剂改善了多种癌症的临床结局，但也与更高的免疫相关不良反应风险相关，尤其是联合使用时。本研究的目的是调查与使用双重同时性免疫检查点抑制剂疗法相比，单一免疫检查点抑制剂疗法中心肌炎的发生率。
使用来自美国一家大型商业保险公司的医疗和药房理赔数据（2011 - 2022年）进行了一项队列研究。Cox回归量化了接受联合治疗（纳武单抗和伊匹单抗）的癌症患者与仅接受单一免疫检查点抑制剂治疗的患者相比发生心肌炎或心力衰竭的相对风险。53018名患者的平均随访时间为226天（四分位间距，93 - 495天）。有148例心肌炎病例（0.3%），联合治疗组中有33例（0.7%），单药治疗组中有115例（0.2%）。联合治疗组每1000名患者发生心肌炎的风险为7.40，单药治疗组为2.37（风险比，3.12 [95% CI，2.12 - 4.60]）。使用多变量回归分析，联合治疗组心肌炎的风险比为2.38（1.57 - 3.63）。联合治疗和单一治疗在心力衰竭风险方面未发现差异。
与单药治疗相比，两种免疫检查点抑制剂联合治疗与心肌炎风险增加相关，大多数病例发生在治疗的前6个月。
