Rheumatic disorders associated with immune checkpoint inhibitors: what about myositis?An analysis of the WHO’s adverse drug reactions database

As shown by Kostine et al ,1 and recently underlined by Ceccarelli et al ,2 rheumatic inflammatory disorders induced by anticancer therapy are becoming a major concern for rheumatologists at the era of immune checkpoint inhibitors (ICIs). Beyond inflammatory arthritis, which may concern 10%–20% of patients, myositis represents a rare (<1%) but potentially life-threatening event. We thus aimed at investigating the risk of ICI-related myositis in real-life setting using VigiBase, the WHO’s pharmacovigilance database. First, we analysed the myositis case associated with ICIs (Anti-Programmed Death (PD)-1, anti-Programmed Death Ligand (PDL)-1, and anti-Cytotoxic-T-Lymphocyte-Associated Protein (CTLA)-4 agents) reported to VigiBase. From 14 786 263 adverse drug reactions (ADRs) recorded between 1 January 2008 and 12 February 2019, we identified 54 085 ICI-related ADRs including 345 myositis (0.6%) (table 1). Among myositis cases, 85.2% occurred with anti-PD-1 or anti-CTLA-4 monotherapies, while 14.8% with combination therapy. Lung (34.8%) and skin cancers (34.2%) were the most frequent indications for ICI therapy. ICI-related myositis was more frequent in male patients, and over 65 years. The median time to onset was 4–5 weeks ranging from 1 day to 20 months, consistently with other reports.3 Almost all ICI-related myositis (95.3%) were considered serious (ie, requiring at least a hospitalisation), with a fatality rate of 22.3%. Myocarditis and myasthenia were associated with ICI-related myositis in 11.3% and 11.9% of cases and resulted in death in 51.3% and 26.8%, respectively. View this table: Table 1 Characteristics of immune checkpoint inhibitor (ICI)-exposed myositis cases Second, using case/non-case …