Inflammatory myopathy associated with PD-1 inhibitors

Morinobu Seki, Akinori Uruha, Yuko Ohnuki, Sachiko Kamada, Tomoko Noda, Asako Onda, Masayuki Ohira, Aiko Isami, Sumie Hiramatsu, Makoto Hibino, Shunya Nakane, Seiya Noda, Sachiko Yutani, Akira Hanazono, Hiroshi Yaguchi, Masaki Takao, Takashi Shiina, Masahisa Katsuno, Jin Nakahara, Shiro MatsubaraIchizo Nishino, Shigeaki Suzuki

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Objective: To characterize the inflammatory myopathy associated with programmed cell death 1 inhibitors (PD-1 myopathy). Methods: We studied 19 Japanese patients with PD-1 myopathy (13 men and 6 women, mean age 70 years), who were referred to Keio University. As control groups, we used 68 patients with anti-signal recognition particle antibodies, 51 patients with anti-aminoacyl transfer RNA synthetase antibodies and 460 healthy subjects. Results: In regard to muscle-disease severity, 10 patients showed a mild form of disease and 9 patients showed a severe form. Non-small cell lung cancer was the most common underlying cancer. PD-1 inhibitor consisted of 11 nivolumab and 8 pembrolizumab. PD-1 myopathy occurred 29 days on average after the first administration of PD-1 inhibitor. The initial manifestation of muscle weakness was ptosis in 10 patients, 15 patients had ptosis, 13 diplopia, 8 facial muscle weakness, 10 bulbar symptoms, 13 limb weakness, 14 neck weakness, 4 cardiac involvement, 6 respiratory involvement and 16 myalgia. Ocular, facial, cardiac and respiratory involvement and myalgia were more frequently observed than controls. Serum creatine kinase was increased to 5247 IU/L on average. Autoantibodies related to inflammatory myopathy were negative, while anti-striational antibodies were found in 13 (68%)patients. HLA-C*12:02 alleles were more frequently detected than healthy controls. Muscle pathology was characterized by multifocal necrotic myofibers with endomysial inflammation and expression of MHC class I. Immunosuppressive therapy with corticosteroids was generally effective for muscle weakness. Conclusions: Based on our clinical, histological and immunological findings, PD-1 myopathy is a discrete subset of inflammatory myopathy.

Original languageEnglish
Pages (from-to)105-113
Number of pages9
JournalJournal of Autoimmunity
Volume100
DOIs
Publication statusPublished - 2019 Jun

Keywords

  • Autoantibodies
  • Creatine kinase
  • Human leucocyte antigen
  • Inflammatory myopathy
  • Programmed cell death 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Seki, M., Uruha, A., Ohnuki, Y., Kamada, S., Noda, T., Onda, A., Ohira, M., Isami, A., Hiramatsu, S., Hibino, M., Nakane, S., Noda, S., Yutani, S., Hanazono, A., Yaguchi, H., Takao, M., Shiina, T., Katsuno, M., Nakahara, J., ... Suzuki, S. (2019). Inflammatory myopathy associated with PD-1 inhibitors. Journal of Autoimmunity, 100, 105-113. https://doi.org/10.1016/j.jaut.2019.03.005