Immune Checkpoint Inhibitor Related Myositis and Associated Triad Overlap Syndrome

Objective Immune checkpoint inhibitor (ICI) myositis is a rare but highly morbid condition, particularly with the ICI myositis triad syndrome of myositis, myocarditis, and myasthenia gravis. We report the clinical characteristics of ICI myositis and all‐cause mortality in these patients. Methods We performed a national retrospective cohort study of US Veterans treated with an ICI between June 2011 and February 2022. Cases were identified by elevated creatinine kinase (CK) following ICI therapy and/or “myositis” in notes. Chart review determined if candidates had ICI‐associated myositis and were subsequently classified as isolated ICI myositis or ICI triad syndrome. Results Of 29,296 Veterans treated with ICIs, 68 (0.2%) ICI‐induced myositis cases were identified including 23 ICI triad syndrome and 45 isolated ICI myositis patients. Median survival duration for ICI triad syndrome was 2.5 (1.7‐18.5, 95% CI) months in comparison to 20.4 (6.2‐60, 95% CI) months for isolated ICI myositis and 12.6 (12.3‐12.8, 95%CI) months median survival for patients treated with ICI without myositis. ICI triad syndrome patients had 60.0% mortality during the six months following initiation of ICI treatment, in comparison to 30.2% mortality in isolated ICI myositis, and 31.5% mortality in patients without myositis. Six months after the first ICI treatment, subsequent mortality trends were similar in the three groups. Conclusion ICI triad syndrome is associated with higher overall mortality and shortened median survival times during the first six months after initial ICI therapy, whereas isolated ICI myositis is associated with similar mortality outcomes to patients treated with ICI who did not develop myositis.