Suzuki Shigeaki, Ishikawa Nobuhisa, Konoeda Fumie, Seki Nobuhiko, Fukushima Satoshi, Takahashi Kikuko, Uhara Hisashi, Hasegawa Yoshikazu, Inomata Shinichiro, Otani Yasushi, Yokota Kenji, Hirose Takashi, Tanaka Ryo, Suzuki Norihiro, Matsui Makoto
From the Department of Neurology (S.S., N. Suzuki), Keio University School of Medicine, Tokyo; Department of Respiratory Medicine (N.I.), Hiroshima Prefectural Hospital, Hiroshima; Department of Neurology (F.K.), Saiseikai Central Hospital, Tokyo; Division of Medical Oncology (N. Seki), Teikyo University School of Medicine, Tokyo; Department of Dermatology and Plastic Surgery (S.F.), Faculty of Life Sciences, Kumamoto University, Kumamoto; Department of Plastic and Reconstructive Surgery (K.T.), Hakodate Central General Hospital, Hokkaido; Department of Dermatology (H.U.), Sapporo Medical University School of Medicine, Hokkaido; Department of Medical Oncology (Y.H.), Izumi Municipal Hospital, Osaka; Department of Respiratory Medicine (S.I.), Sapporo Kosei Hospital, Hokkaido; Department of Oncology (Y.O.), Toyonaka Municipal Hospital, Osaka; Department of Dermatology (K.Y.), Nagoya University Graduate School of Medicine, Aichi; Department of Respiratory Medicine and Oncology (T.H.), Nippon Medical School Tama Nagayama Hospital, Tokyo; Department of Dermatology (R.T.), Kawasaki Medical School, Okayama; and Department of Neurology (M.M.), Kanazawa Medical College, Ishikawa, Japan.
Neurology. 2017 Sep 12;89(11):1127-1134. doi: 10.1212/WNL.0000000000004359. Epub 2017 Aug 18.
To report the clinical features of myasthenia gravis (MG) induced by treatment with immune checkpoint inhibitors using 2-year safety databases based on postmarketing surveys in Japan.
We studied 10,277 patients with cancer who had received monotherapy with either nivolumab or ipilimumab between September 2014 and August 2016. As the control group, 105 patients with idiopathic MG were used.
There were 12 MG cases (0.12%) among 9,869 patients with cancer who had been treated with nivolumab, but none among 408 patients treated with ipilimumab. These 12 patients included 6 men and 6 women with a mean age of 73.5 ± 6.3 years. MG onset occurred in the early phase after nivolumab treatment and rapidly deteriorated. Nivolumab-related MG (nivoMG) included 4 patients with mild involvement and 8 patients with severe involvement. Bulbar symptoms and myasthenic crisis were observed more frequently in nivoMG than idiopathic MG. Ten patients were positive for anti-acetylcholine receptor antibodies. Serum creatine kinase levels were markedly elevated to an average level of 4,799 IU/L. Among the 12 patients with nivoMG, 4 had myositis and 3 had myocarditis, with 1 of these patients having both. Immunosuppressive therapy was effective. Postintervention status showed that pharmacologic remission or minimal manifestations were obtained in 4 patients; however, 2 patients died. Immune-related adverse events triggered by nivolumab impaired the patients' daily living activity.
The prompt and correct recognition of MG following treatment with immune checkpoint inhibitors in patients with cancer is important.
利用日本上市后调查的2年安全性数据库，报告免疫检查点抑制剂治疗所致重症肌无力（MG）的临床特征。
我们研究了2014年9月至2016年8月期间接受纳武单抗或伊匹单抗单药治疗的10277例癌症患者。作为对照组，使用了105例特发性MG患者。
在接受纳武单抗治疗的9869例癌症患者中有12例MG病例（0.12%），但在接受伊匹单抗治疗的408例患者中无病例。这12例患者包括6名男性和6名女性，平均年龄为73.5±6.3岁。MG在纳武单抗治疗后的早期阶段发病并迅速恶化。纳武单抗相关MG（nivoMG）包括4例轻度受累患者和8例重度受累患者。nivoMG患者出现延髓症状和肌无力危象的频率高于特发性MG患者。10例患者抗乙酰胆碱受体抗体呈阳性。血清肌酸激酶水平显著升高，平均达到4799 IU/L。在12例nivoMG患者中，4例有肌炎，3例有心肌炎，其中1例两者都有。免疫抑制治疗有效。干预后状态显示，4例患者获得了药物缓解或仅有轻微表现；然而，2例患者死亡。纳武单抗引发的免疫相关不良事件损害了患者的日常生活活动能力。
癌症患者接受免疫检查点抑制剂治疗后迅速、正确地识别MG很重要。
