Inflammatory myopathy associated with PD-1 inhibitors Publication date: June 2019 Source: Journal of Autoimmunity, Volume 100 Author(s): 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 Matsubara 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.