Immune checkpoint inhibitor-induced myositis, the earliest and most lethal complication among rheumatic and musculoskeletal toxicities

Yves Allenbach, Céline Anquetil, Ali Manouchehri, Olivier Benveniste, Olivier Lambotte, Bénédicte Lebrun-Vignes, Jean Philippe Spano, Stéphane Ederhy, David Klatzmann, Michelle Rosenzwajg, Bruno Fautrel, Jacques Cadranel, Douglas B. Johnson, Javid J. Moslehi, Joe Elie Salem

Résultats de recherche: Contribution à un journalArticle 'review'Revue par des pairs

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Résumé

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.

langue originaleAnglais
Numéro d'article102586
journalAutoimmunity Reviews
Volume19
Numéro de publication8
Les DOIs
étatPublié - 1 août 2020
Modification externeOui

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