Immune checkpoint inhibitors have revolutionized the landscape of cancer treatment. Alongside their many advantages, they elicit immune-related adverse events, including myopathy, which potentially result in substantial morbidity if not recognized and treated promptly. Current knowledge of immune checkpoint inhibitor-associated myopathy is limited. We conducted a 5-year retrospective study of patients with immune checkpoint inhibitor-associated myopathy. Clinical features, survival and ancillary test findings were analysed and compared with those of immune-mediated necrotizing myopathy patients without immune checkpoint inhibitor exposure seen during the same time period. We identified 24 patients with immune checkpoint inhibitor-associated myopathy (median age 69 years; range 28–86) and 38 patients with immune-mediated necrotizing myopathy. Ocular involvement occurred in 9/24 patients with immune checkpoint inhibitor exposure, without electrodiagnostic evidence of neuromuscular transmission defect, and in none of the immune-mediated necrotizing myopathy patients (P < 0.001). Myocarditis occurred in eight immune checkpoint inhibitor-associated myopathy patients and in none of the immune-mediated necrotizing myopathy patients (P < 0.001). Median creatine kinase was 686 IU/l in the immune checkpoint inhibitor cohort (seven with normal creatine kinase) compared to 6456 IU/l in immune-mediated necrotizing myopathy cohort (P < 0.001). Lymphopenia was observed in 18 and 7 patients with and without immune checkpoint inhibitor exposure, respectively (P < 0.001). Myopathological findings were similar between patients with and without immune checkpoint inhibitor exposure, consisting of necrotic fibres with no or subtle inflammation. Necrotic fibres however arranged in clusters in 10/11 immune checkpoint inhibitor-associated myopathy patients but in none of the immune checkpoint inhibitor-naïve patients (P < 0.001). Despite the lower creatine kinase levels in immune checkpoint inhibitor-exposed patients, the number of necrotic fibres was similar in both groups. Immune checkpoint inhibitor-associated myopathy patients had a higher frequency of mitochondrial abnormalities and less number of regenerating fibres than immune-mediated necrotizing myopathy patients (P < 0.001). Anti-hydroxy-3-methylglutaryl-CoA reductase or signal recognition particle antibodies were absent in patients with immune checkpoint inhibitor exposure but positive in two-thirds of immune checkpoint inhibitor-naïve patients. Most patients with immune checkpoint inhibitor-associated myopathy responded favourably to immunomodulatory treatments, but four died from myopathy-related complications and one from myocarditis. Intubated patients had significantly shorter survival compared to non-intubated patients (median survival of 22 days; P = 0.004). In summary, immune checkpoint inhibitor-associated myopathy is a distinct, treatable immune-mediated myopathy with common ocular involvement, frequent lymphopenia and necrotizing histopathology, which contrary to immune-mediated necrotizing myopathy, is featured by clusters of necrotic fibres and not accompanied by anti-hydroxy-3-methylglutaryl-CoA reductase or signal recognition particle antibodies. Normal or mildly elevated creatine kinase level does not exclude the diagnosis.

Objectives To determine the prevalence and natural history of sporadic inclusion body myositis (sIBM) and to test the hypothesis that patients with sIBM have higher cancer or mortality rates than the general population. Methods We sought patients with sIBM defined by the 2011 European Neuromuscular Centre (ENMC) diagnostic criteria among Olmsted County, Minnesota, residents in 40-year time period. Results We identified 20 patients (10 clinicopathologically defined, 9 clinically defined, and 1 probable) according to the ENMC criteria and 1 patient with all features of clinicopathologically defined sIBM except for symptom onset at <45 years of age. The prevalence of sIBM in 2010 was 18.20 per 100,000 people ≥50 years old. Ten patients developed cancers. The incidence of cancers in sIBM did not differ from that observed in the general population (odds ratio 1.89, 95% confidence interval [CI] 0.639–5.613, p = 0.24). Two-thirds of patients developed dysphagia, and half required a feeding tube. Nine patients required a wheelchair. The median time from symptom onset to wheelchair dependence was 10.5 (range 1–29) years. Overall life expectancy was shorter in the sIBM group compared to the general population (84.1 [95% CI 78–88.4] vs 87.5 [95% CI 85.2–89.5] years, p = 0.03). Thirteen patients died; 9 deaths were sIBM related (7 respiratory and 2 unspecified sIBM complications). Female sex (p = 0.03) and dysphagia (p = 0.05) were independent predictors of death. Conclusion Olmsted County has the highest prevalence of sIBM reported to date. Patients with sIBM have similar risk of cancer, but slightly shorter life expectancy compared to matched patients without sIBM. Classification of Evidence This study provides Class II evidence that patients with sIBM have similar risks of cancers and slightly shorter life expectancy compared to controls.

Objective: To evaluate survival and associated comorbidities in inclusion body myositis (IBM) in a population-based, case-control study. Methods: We utilized the expanded Rochester Epidemiology Project medical records-linkage system, including 27 counties in Minnesota and Wisconsin, to identify patients with IBM, other inflammatory myopathies (IIM), and age/sex-matched population-controls. We compared the frequency of various comorbidities and survival among groups. Results: We identified 50 IBM patients, 65 IIM controls and 294 population controls. Dysphagia was most common in IBM (64%) patients. The frequency of neurodegenerative disorders (dementia/parkinsonism) and solid cancers was not different between groups. Rheumatoid arthritis was the most common rheumatic disease in all groups. A total of 36% of IBM patients had a peripheral neuropathy, 6% had Sjögren’s syndrome and 10% had a haematologic malignancy. T-cell large granular lymphocytic leukaemia was only observed in the IBM group. None of the IBM patients had hepatitis B or C, or HIV. IBM patients were 2.7 times more likely to have peripheral neuropathy, 6.2 times more likely to have Sjögren’s syndrome and 3.9 times more likely to have a haematologic malignancy than population controls. IBM was associated with increased mortality, with a 10-year survival of 36% from index, compared with 67% in IIM and 59% in population controls. Respiratory failure or pneumonia (44%) was the most common cause of death. Conclusions: IBM is associated with lower survival, and higher frequency of peripheral neuropathy, Sjögren’s syndrome and haematologic malignancies than the general population. Close monitoring of IBM-related complications is warranted.