IMMUNE CHECKPOINT INHIBITOR-INDUCED MYOSITIS, THE EARLIEST AND MOST LETHAL COMPLICATION AMONG RHEUMATIC AND MUSCULOSKELETAL TOXICITIES
- Celine Anquetil, France
Abstract
Background and Aims
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.
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 1,288 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), scleroderma (n=17; ROR=2.0 [1.2-3.2]; IC025=0.17), and arthritis (n=606; ROR=1.4 [1.3-1.5]; IC025=0.34). 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<0.05) and more frequently reported on anti-PD1/PDL1 monotherapy vs. anti-CTLA4 monotherapy (2.1-4.4, p<0.05). 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<0.0001). 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<0.0001).
Conclusions
Clinicians should be aware of the spectrum of RMS-irAE. Myositis can be particularly life-threatening, particularly when associated with myocarditis.