Nivolumab-related myasthenia gravis with myositis and myocarditis in Japan

Shigeaki Suzuki, Nobuhisa Ishikawa, Fumie Konoeda, Nobuhiko Seki, Satoshi Fukushima, Kikuko Takahashi, Hisashi Uhara, Yoshikazu Hasegawa, Shinichiro Inomata, Yasushi Otani, Kenji Yokota, Takashi Hirose, Ryo Tanaka, Norihiro Suzuki, Makoto Matsui

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Abstract

OBJECTIVE: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: The prompt and correct recognition of MG following treatment with immune checkpoint inhibitors in patients with cancer is important.

Original languageEnglish
Pages (from-to)1127-1134
Number of pages8
JournalNeurology
Volume89
Issue number11
DOIs
Publication statusPublished - 2017 Sep 12

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Myositis
Myasthenia Gravis
Myocarditis
Japan
nivolumab
Neoplasms
Muscle Weakness
Cholinergic Receptors
Therapeutics
Immunosuppressive Agents
Creatine Kinase
Activities of Daily Living

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Suzuki, S., Ishikawa, N., Konoeda, F., Seki, N., Fukushima, S., Takahashi, K., ... Matsui, M. (2017). Nivolumab-related myasthenia gravis with myositis and myocarditis in Japan. Neurology, 89(11), 1127-1134. https://doi.org/10.1212/WNL.0000000000004359

Nivolumab-related myasthenia gravis with myositis and myocarditis in Japan. / 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.

In: Neurology, Vol. 89, No. 11, 12.09.2017, p. 1127-1134.

Research output: Contribution to journalArticle

Suzuki, S, Ishikawa, N, Konoeda, F, Seki, N, Fukushima, S, Takahashi, K, Uhara, H, Hasegawa, Y, Inomata, S, Otani, Y, Yokota, K, Hirose, T, Tanaka, R, Suzuki, N & Matsui, M 2017, 'Nivolumab-related myasthenia gravis with myositis and myocarditis in Japan', Neurology, vol. 89, no. 11, pp. 1127-1134. https://doi.org/10.1212/WNL.0000000000004359
Suzuki S, Ishikawa N, Konoeda F, Seki N, Fukushima S, Takahashi K et al. Nivolumab-related myasthenia gravis with myositis and myocarditis in Japan. Neurology. 2017 Sep 12;89(11):1127-1134. https://doi.org/10.1212/WNL.0000000000004359
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. / Nivolumab-related myasthenia gravis with myositis and myocarditis in Japan. In: Neurology. 2017 ; Vol. 89, No. 11. pp. 1127-1134.
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AU - Suzuki, Shigeaki

AU - Ishikawa, Nobuhisa

AU - Konoeda, Fumie

AU - Seki, Nobuhiko

AU - Fukushima, Satoshi

AU - Takahashi, Kikuko

AU - Uhara, Hisashi

AU - Hasegawa, Yoshikazu

AU - Inomata, Shinichiro

AU - Otani, Yasushi

AU - Yokota, Kenji

AU - Hirose, Takashi

AU - Tanaka, Ryo

AU - Suzuki, Norihiro

AU - Matsui, Makoto

PY - 2017/9/12

Y1 - 2017/9/12

N2 - OBJECTIVE: 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.METHODS: 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.RESULTS: 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.CONCLUSIONS: The prompt and correct recognition of MG following treatment with immune checkpoint inhibitors in patients with cancer is important.

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