Incidence and Distinct Features of Immune Checkpoint Inhibitor-Related Myositis From Idiopathic Inflammatory Myositis: A Single-Center Experience With Systematic Literature Review and Meta-Analysis

Abstract

Immune checkpoint inhibitor (ICI)-related myositis is a rare, potentially fatal condition that warrants further studies. Its incidence, clinical features, and prognosis remain poorly understood. To address these gaps, we conducted a systematic review and meta-analysis to evaluate the risk of myositis associated with ICI for solid tumors by analyzing phase III randomized controlled trials of anti-programmed death-1/ligand-1 (PD-1/PD-L1) and anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4). To complement this analysis with clinical data, we evaluated published ICI case reports along with cases from our institutional registry. This registry comprised 422 patients treated with ICIs alone or in combination from September 2014 to June 2021. The analysis revealed an incidence of ICI-related myositis in 6,838 patients in 18 randomized controlled trials of 0.38% (odds ratio 1.96; 95% confidence interval 1.02–3.75) for patients receiving ICIs compared with controls. Detailed analysis of 88 cases from the literature search and our registry showed that myositis induced by PD-1 inhibitors was more frequent than that induced by anti-CTLA-4 agents, revealing a clinically diverse trend including myasthenia gravis and myocarditis. Importantly, having ptosis at the time of onset was significantly associated with the development of concomitant myocarditis (odds ratio 3.81; 95% CI 1.48–9.83), which is associated with poor prognosis. Regarding treatment, most patients received glucocorticoids, and some received immunosuppressants. Our study revealed the incidence of ICI-mediated myositis and the clinical features of myocarditis, highlighting the need for recognition and early intervention.

Immune Checkpoint Inhibitor–Associated Myositis

“…The patients who died of the ICI myositis were significantly older and more likely to have ptosis than those who did not 15 . Most common causes of death were also different in patients with isolated ICI myositis and overlap myositis 16 . Among patients with isolated ICI myositis, the most common causes of death were cancer progression, followed by myositis and infection 16 .…”

“…A meta-analysis of 18 randomized clinical trials of various ICI regimens (n = 6838) showed an overall incidence as 0.38%. 16 The World Health Organization Pharmacovigilance Database with adverse drug reactions reported until February 2019 showed incidence of ICI myositis as 0.6%. 7 However, pharmacovigilance databases are often biased, skewing toward more serious manifestations and foregoing less serious ones.…”

“…15 Most common causes of death were also different in patients with isolated ICI myositis and overlap myositis. 16 Among patients with isolated ICI myositis, the most common causes of death were cancer progression, followed by myositis and infection. 16 However, in overlap patients, the most common cause of death was irAE, followed by progression of cancer and infection.…”

“…16 However, in overlap patients, the most common cause of death was irAE, followed by progression of cancer and infection. 16…”

“…Incidence of ICI myositis has been varied in the literature based on the methodology of the study. A meta-analysis of 18 randomized clinical trials of various ICI regimens (n = 6838) showed an overall incidence as 0.38% 16 . The World Health Organization Pharmacovigilance Database with adverse drug reactions reported until February 2019 showed incidence of ICI myositis as 0.6% 7 .…”