| アブストラクト | BACKGROUND: In addition to restoring anti-tumor immune responses, immune checkpoint inhibitors (ICI) may also induce immune-related adverse events (irAE) that can affect any organ. We aim to determine the spectrum, timing, clinical features, and fatalities of rheumatic and musculoskeletal immune-related adverse events (RMS-irAE) associated with ICI. PATIENTS METHODS: We performed an observational, retrospective, pharmacovigilance study using the World Health Organization international pharmacovigilance database, VigiBase, from inception to January 2019. RMS-irAE reporting rate on ICI versus full database was performed using disproportionality analysis with computation of reporting-odds-ratios (ROR) and a Bayesian disproportional estimate (information component, IC). IC025 (lower end of the IC 95% credibility interval) >0 is deemed significant. RESULTS: We identified 1288 RMS-irAE significantly associated with ICI: polymyalgia rheumatica (n = 76, ROR = 14.6 [11.6-18.4], IC025 = 3.34), sarcoidosis (n = 94; ROR = 9.6 [7.9-11.9]; IC025 = 2.85), Sjogren's syndrome (n = 49; ROR = 6.9 [5.2-9.2]; IC025 = 2.24), myositis (n = 465; ROR = 4.9 [4.5-5.4]; IC025 = 2.12), arthritis (n = 606; ROR = 1.4 [1.3-1.5]; IC025 = 0.34) and scleroderma (n = 17; ROR = 2.0 [1.2-3.2]; IC025 = 0.17). Arthritis, myositis, and Sjogren's syndrome were over-reported in patients treated with ICI combination versus those treated with ICI monotherapy (ROR = 1.6-2.9, p < .05) and more frequently reported on anti-PD1/PDL1 monotherapy vs. anti-CTLA4 monotherapy (2.1-4.4, p < .05). Median time to onset occurred early for myositis (31 days [19.2-57.8]) and was the most delayed for scleroderma (395 days [323.8-457.2], p < .0001). The fatality rate for RMS-irAE ranged from 24% for myositis (n = 106/441) (up to 56.7% with concurrent myocarditis) to [0-6.7%] for other RMS-irAE (p < .0001). CONCLUSIONS: Clinicians should be aware of the spectrum of RMS-irAE. Myositis can be particularly life-threatening, particularly when associated with myocarditis. |
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| 投稿者 | Allenbach, Yves; Anquetil, Celine; Manouchehri, Ali; Benveniste, Olivier; Lambotte, Olivier; Lebrun-Vignes, Benedicte; Spano, Jean-Philippe; Ederhy, Stephane; Klatzmann, David; Rosenzwajg, Michelle; Fautrel, Bruno; Cadranel, Jacques; Johnson, Douglas B; Moslehi, Javid J; Salem, Joe-Elie |
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| 組織名 | Department of Internal Medicine and Clinical Immunlogy, Sorbonne Universite,;Pitie-Salpetriere University Hospital, Paris, France; Sorbonne Universite,;Institut National de la Sante et de la Recherche Medicale, Association Institut;de Myologie, Centre de Recherche en Myologie, UMRS974 Paris, France. Electronic;address: yves.allenbach@aphp.fr.;de Myologie, Centre de Recherche en Myologie, UMRS974 Paris, France.;Cardio-Oncology Program, Department of Medicine, Vanderbilt University Medical;Center, Nashville, TN, USA.;Department of Internal Medicine and Clinical Immunology, Assistance;Publique-Hopitaux de Paris, Hopital Universitaire Bicetre, Universite Paris Sud,;Inserm, CEA, UMR, 1184 Le Kremlin-Bicetre, France.;Regional Pharmacovigilance Centre, Department of Pharmacology, Sorbonne;Universite, INSERM CIC Paris-Est, Assistance Publique Hopitaux de Paris,;Pitie-Salpetriere Hospital, Paris, France.;Oncology departement, Sorbonne Universite, Pitie-Salpetriere University Hospital,;Paris, France.;Department of cardiology, Saint-Antoine Hospital, APHP. Sorbonne universite,;Department of Biotherapy (CIC-BTi) and Inflammation-Immunopathology-Biotherapy;(i2B), Sorbonne Universite, Pitie-Salpetriere University Hospital, INSERM, UMR_S;959, Immunology-Immunopathology-Immunotherapy (i3), Paris, France.;Department of Rheumatology, Sorbonne Universite, Pitie-Salpetriere University;Hospital, Inserm UMR 1136, Pierre Louis Institute of Health and Epidemiology;Department of Pneumology, Constitutive Center on Rare Pulmonary Diseases,;Sorbonne Universite, Tenon University Hospital, Paris, France.;Center, Nashville, TN, USA; Regional Pharmacovigilance Centre, Department of;Pharmacology, Sorbonne Universite, INSERM CIC Paris-Est, Assistance Publique;Hopitaux de Paris, Pitie-Salpetriere Hospital, Paris, France. Electronic address:;joe-elie.salem@aphp.fr. |
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