Niimura Takahiro, Zamami Yoshito, Miyata Koji, Mikami Takahisa, Asada Mizuho, Fukushima Keijo, Yoshino Masaki, Mitsuboshi Satoru, Okada Naoto, Hamano Hirofumi, Sakurada Takumi, Matsuoka-Ando Rie, Aizawa Fuka, Yagi Kenta, Goda Mitsuhiro, Chuma Masayuki, Koyama Toshihiro, Izawa-Ishizawa Yuki, Yanagawa Hiroaki, Fujino Hiromichi, Yamanishi Yoshihiro, Ishizawa Keisuke
Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital, Tokushima, Japan.
J Clin Pharmacol. 2023 Apr;63(4):473-479. doi: 10.1002/jcph.2187. Epub 2022 Dec 21.
Myasthenia gravis (MG) is a rare but fatal adverse event of immune checkpoint inhibitors (ICIs). We assessed whether patient characteristics differed between those with ICI-related myasthenia gravis and those with idiopathic myasthenia gravis. Reports from the US Food and Drug Administration Adverse Event Reporting System were analyzed. Multivariate analyses were conducted to evaluate the associations between age, sex, and ICI treatment and the reporting rate of myasthenia gravis. Among 5 464 099 cases between 2011 and 2019, 53 447 were treated with ICIs. Myasthenia gravis was reported more often in ICI users. Multiple logistic regression analyses showed that the reporting rate of ICI-related myasthenia gravis did not differ significantly between men and women; however, it was higher in older people than in younger people (adjusted odds ratio, 2.4 [95%CI, 1.84-3.13]). We also investigated useful signs for the early detection of myositis and myocarditis, which are fatal when overlapping with ICI-related myasthenia gravis. Patients with elevated serum creatine kinase or troponin levels were more likely to have concurrent myositis and myocarditis. Unlike idiopathic myasthenia gravis, there was no sex difference in the development of ICI-related myasthenia gravis, which may be more common in older people. Considering the physiological muscle weakness that occurs in the elderly, it may be necessary to monitor ICI-related myasthenia gravis more closely in older people.
重症肌无力(MG)是免疫检查点抑制剂(ICI)罕见但致命的不良事件。我们评估了ICI相关重症肌无力患者与特发性重症肌无力患者的特征是否存在差异。对美国食品药品监督管理局不良事件报告系统的报告进行了分析。进行多变量分析以评估年龄、性别、ICI治疗与重症肌无力报告率之间的关联。在2011年至2019年期间的5464099例病例中,53447例接受了ICI治疗。ICI使用者中重症肌无力的报告更为常见。多项逻辑回归分析表明,ICI相关重症肌无力的报告率在男性和女性之间无显著差异;然而,老年人的报告率高于年轻人(调整后的优势比为2.4 [95%置信区间,1.84 - 3.13])。我们还研究了有助于早期发现肌炎和心肌炎的体征,当它们与ICI相关重症肌无力重叠时可能是致命的。血清肌酸激酶或肌钙蛋白水平升高的患者更有可能并发肌炎和心肌炎。与特发性重症肌无力不同,ICI相关重症肌无力的发生不存在性别差异,且在老年人中可能更为常见。考虑到老年人出现的生理性肌肉无力,可能有必要对老年人更密切地监测ICI相关重症肌无力。