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

3 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 1

Fingerprint

Myositis
Muscular Diseases
Muscle Weakness
Myalgia
Signal Recognition Particle
HLA-C Antigens
Facial Muscles
Amino Acyl-tRNA Synthetases
Muscles
Diplopia
Antibodies
Immunosuppressive Agents
Creatine Kinase
Non-Small Cell Lung Carcinoma
Autoantibodies
Anti-Idiotypic Antibodies
Healthy Volunteers
Adrenal Cortex Hormones
Cell Death
Neck

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Inflammatory myopathy associated with PD-1 inhibitors. / Seki, Morinobu; Uruha, Akinori; Ohnuki, Yuko; Kamada, Sachiko; Noda, Tomoko; Onda, Asako; Ohira, Masayuki; Isami, Aiko; Hiramatsu, Sumie; Hibino, Makoto; Nakane, Shunya; Noda, Seiya; Yutani, Sachiko; Hanazono, Akira; Yaguchi, Hiroshi; Takao, Masaki; Shiina, Takashi; Katsuno, Masahisa; Nakahara, Jin; Matsubara, Shiro; Nishino, Ichizo; Suzuki, Shigeaki.

In: Journal of Autoimmunity, Vol. 100, 01.06.2019, p. 105-113.

Research output: Contribution to journalArticle

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, Matsubara, S, Nishino, I & Suzuki, S 2019, 'Inflammatory myopathy associated with PD-1 inhibitors', Journal of Autoimmunity, vol. 100, pp. 105-113. https://doi.org/10.1016/j.jaut.2019.03.005
Seki, Morinobu ; Uruha, Akinori ; Ohnuki, Yuko ; Kamada, Sachiko ; Noda, Tomoko ; Onda, Asako ; Ohira, Masayuki ; Isami, Aiko ; Hiramatsu, Sumie ; Hibino, Makoto ; Nakane, Shunya ; Noda, Seiya ; Yutani, Sachiko ; Hanazono, Akira ; Yaguchi, Hiroshi ; Takao, Masaki ; Shiina, Takashi ; Katsuno, Masahisa ; Nakahara, Jin ; Matsubara, Shiro ; Nishino, Ichizo ; Suzuki, Shigeaki. / Inflammatory myopathy associated with PD-1 inhibitors. In: Journal of Autoimmunity. 2019 ; Vol. 100. pp. 105-113.
@article{1e20f8cddac7442492bcd51f209df4c1,
title = "Inflammatory myopathy associated with PD-1 inhibitors",
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.",
keywords = "Autoantibodies, Creatine kinase, Human leucocyte antigen, Inflammatory myopathy, Programmed cell death 1",
author = "Morinobu Seki and Akinori Uruha and Yuko Ohnuki and Sachiko Kamada and Tomoko Noda and Asako Onda and Masayuki Ohira and Aiko Isami and Sumie Hiramatsu and Makoto Hibino and Shunya Nakane and Seiya Noda and Sachiko Yutani and Akira Hanazono and Hiroshi Yaguchi and Masaki Takao and Takashi Shiina and Masahisa Katsuno and Jin Nakahara and Shiro Matsubara and Ichizo Nishino and Shigeaki Suzuki",
year = "2019",
month = "6",
day = "1",
doi = "10.1016/j.jaut.2019.03.005",
language = "English",
volume = "100",
pages = "105--113",
journal = "Journal of Autoimmunity",
issn = "0896-8411",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Inflammatory myopathy associated with PD-1 inhibitors

AU - Seki, Morinobu

AU - Uruha, Akinori

AU - Ohnuki, Yuko

AU - Kamada, Sachiko

AU - Noda, Tomoko

AU - Onda, Asako

AU - Ohira, Masayuki

AU - Isami, Aiko

AU - Hiramatsu, Sumie

AU - Hibino, Makoto

AU - Nakane, Shunya

AU - Noda, Seiya

AU - Yutani, Sachiko

AU - Hanazono, Akira

AU - Yaguchi, Hiroshi

AU - Takao, Masaki

AU - Shiina, Takashi

AU - Katsuno, Masahisa

AU - Nakahara, Jin

AU - Matsubara, Shiro

AU - Nishino, Ichizo

AU - Suzuki, Shigeaki

PY - 2019/6/1

Y1 - 2019/6/1

N2 - 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.

AB - 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.

KW - Autoantibodies

KW - Creatine kinase

KW - Human leucocyte antigen

KW - Inflammatory myopathy

KW - Programmed cell death 1

UR - http://www.scopus.com/inward/record.url?scp=85065791111&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85065791111&partnerID=8YFLogxK

U2 - 10.1016/j.jaut.2019.03.005

DO - 10.1016/j.jaut.2019.03.005

M3 - Article

C2 - 30862448

AN - SCOPUS:85065791111

VL - 100

SP - 105

EP - 113

JO - Journal of Autoimmunity

JF - Journal of Autoimmunity

SN - 0896-8411

ER -