Case Series of Steroid-Resistant Immune Checkpoint Inhibitor Associated Myocarditis: A Comparative Analysis of Corticosteroid and Tofacitinib Treatment.
Case Series of Steroid-Resistant Immune Checkpoint Inhibitor Associated Myocarditis: A Comparative Analysis of Corticosteroid and Tofacitinib Treatment.
复制标题
类固醇抵抗性免疫检查点抑制剂相关心肌炎病例系列：皮质类固醇和托法替布治疗的比较分析
DOI：
10.3389/fphar.2021.770631
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发表时间：
2021
影响因子：
5.6
通讯作者：
Ge J
中科院分区：
文献类型：
--
作者：
Wang C;Lin J;Wang Y;Hsi DH;Chen J;Liu T;Zhou Y;Ren Z;Zeng Z;Cheng L;Ge J
背景：免疫检查点抑制剂（ICI）相关心肌炎是一种罕见且可能致命的免疫相关不良事件（irAE）。虽然目前的指南推荐皮质类固醇作为一线治疗，但患者对其的反应仍然不同，指南在治疗策略方面也有很大差异。目的：在本研究中，我们对我院ici相关性心肌炎进行回顾性分析，提出一种新的比较分析方法，以帮助个体化治疗。方法：回顾我院2019年7月1日至2021年4月1日确诊的24例ici相关性心肌炎患者的详细记录。尽管我们研究中的所有病例都根据指南接受了推荐的初始皮质类固醇治疗，但在随后的皮质类固醇减量过程中观察到对皮质类固醇的不同反应。基于糖皮质激素减量期间心肌肌钙蛋白T反弹，我们提出了一种新的ici相关心肌炎分类分析，包括两个亚组：糖皮质激素敏感组（n = 8）和糖皮质激素抵抗组（n = 16）。结果：与糖皮质激素敏感患者相比，糖皮质激素抵抗患者的糖皮质激素剂量更大，治疗时间更长，死亡率更高。与皮质类固醇敏感患者相比，皮质类固醇抵抗患者的特征是更明显的上睑下垂、肌肉无力、心脏生物标志物、肌酸激酶和肝酶水平升高。11例皮质类固醇耐药患者使用Tofacitinib （5 mg， 2次/ d）治疗，7例ci相关性心肌炎患者痊愈，显示出良好的治疗效果。结论：我们对ici相关性心肌炎患者皮质类固醇反应性的分组分析可能有助于临床医生对这一高危人群进行个体化治疗。此外，托法替尼在皮质类固醇耐药患者早期使用时可以提供临床益处，并可能为ici相关心肌炎的治疗提供新的选择。
Background: Immune checkpoint inhibitor (ICI)–associated myocarditis is an uncommon and potentially fatal immune-related adverse event (irAE). Although corticosteroids are recommended as the first-line treatment by current guidelines, patients still have variable responses to it, and the guidelines vary significantly in terms of treatment strategies. Objectives: In this study, we performed a retrospective analysis of ICI-associated myocarditis in our hospital to propose a new comparative analysis to aid individualized treatment. Methods: We reviewed detailed records of 24 patients with confirmed ICI-associated myocarditis in our hospital from July 1, 2019, to April 1, 2021. Although all the cases in our study received recommended initial corticosteroid treatment according to the guidelines, different responses to corticosteroid were observed during the process of subsequent corticosteroid tapering. Basing on troponin cardiac troponin T rebound during corticosteroid tapering, we propose a new classification analysis of ICI-associated myocarditis that included two subgroups: corticosteroid-sensitive (n = 8) and corticosteroid-resistant group (n = 16). Results: Compared with corticosteroid-sensitive patients, larger doses of corticosteroid, longer period of treatment, and higher mortality rate were found in corticosteroid-resistant patients. Corticosteroid-resistant patients were characterized by more prominent ptosis, muscle weakness, elevated cardiac biomarkers, creatine kinase, and hepatic enzymes levels than that in the corticosteroid-sensitive patients. Tofacitinib (5 mg twice a day) was used in 11 corticosteroid-resistant patients, with seven patients recovered from ICI-associated myocarditis, showing a promising therapeutic effect. Conclusion: Our group analysis of corticosteroid responsiveness in patients with ICI-associated myocarditis may help clinicians to apply individualized treatment in this high-risk cohort. In addition, tofacitinib could provide clinical benefits when used early in the corticosteroid-resistant patients and may provide a new option for the treatment of ICI-associated myocarditis.