Morinobu Seki1, Akinori Uruha2, Yuko Ohnuki3, Sachiko Kamada4, Tomoko Noda5, Asako Onda6, Masayuki Ohira7, Aiko Isami8, Sumie Hiramatsu9, Makoto Hibino10, Shunya Nakane11, Seiya Noda12, Sachiko Yutani13, Akira Hanazono4, Hiroshi Yaguchi6, Masaki Takao7, Takashi Shiina14, Masahisa Katsuno12, Jin Nakahara1, Shiro Matsubara2, Ichizo Nishino15, Shigeaki Suzuki16. 1. Department of Neurology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. 2. Department of Neurology, Tokyo Metropolitan Neurological Hospital, 2-6-1 Musashidai, Fuchu, Tokyo, 183-0042, Japan. 3. Department of Medical Ethics, Tokai University School of Medicine, 143 Shimokasuya, Isehara-shi, Kanagawa, 259-1193, Japan. 4. Department of Neurology, Akita University School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan. 5. Department of Neurology, Ichinomiya Municipal Hospital, 2-2-22 Bunkyo, Ichinomiya-shi, Aichi, 491-8558, Japan. 6. Department of Neurology, Jikei University Kashiwa Hospital, 163-1 Kashiwashita Kashiwa-shi, Chiba, 277-8567, Japan. 7. Department of Neurology, Saitama International Medical Center, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama, 350-1298, Japan. 8. Department of Neurology, Nagaoka Red Cross Hospital, 2-297-1, Sensyu, Nagaoka-shi, Niigata, 940-2085, Japan. 9. Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-0914, Japan. 10. Department of Respiratory Medicine, Shonan Fujisawa Tokushukai Hospital, 1-5-1 Tsujido Kandai, Fujisawa-shi, Kanagawa, 251-0041, Japan. 11. Department of Molecular Neurology and Therapeutics, Kumamoto University Hospital, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan. 12. Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan. 13. Department of Neurology, Tokai University School of Medicine, 143 Shimokasuya, Isehara-shi, Kanagawa, 259-1193, Japan. 14. Department of Molecular Life Science, Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara-shi, Kanagawa, 259-1193, Japan. 15. Department of Neuromuscular Research, National Institute of Neuroscience, And Department of Genome Medicine Development, Medical Genome Center, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8502, Japan. 16. Department of Neurology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. Electronic address: sgsuzuki@z3.keio.jp.
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.
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.
Authors: Nikeshan Jeyakumar; Mikel Etchegaray; Jason Henry; Laura Lelenwa; Bihong Zhao; Ana Segura; L Maximilian Buja Journal: Case Reports Immunol Date: 2020-07-04
Authors: Bart K Chwalisz; James Hillis; Amanda C Guidon; Leeann B Burton; Teilo H Schaller; Anthony A Amato; Allison Betof Warner; Priscilla K Brastianos; Tracey A Cho; Stacey L Clardy; Justine V Cohen; Jorg Dietrich; Michael Dougan; Christopher T Doughty; Divyanshu Dubey; Jeffrey M Gelfand; Jeffrey T Guptill; Douglas B Johnson; Vern C Juel; Robert Kadish; Noah Kolb; Nicole R LeBoeuf; Jenny Linnoila; Andrew L Mammen; Maria Martinez-Lage; Meghan J Mooradian; Jarushka Naidoo; Tomas G Neilan; David A Reardon; Krista M Rubin; Bianca D Santomasso; Ryan J Sullivan; Nancy Wang; Karin Woodman; Leyre Zubiri; William C Louv; Kerry L Reynolds Journal: J Immunother Cancer Date: 2021-07 Impact factor: 13.751