To identify predictors of early mortality (within 30 days) in patients with myositis/myasthenia (MM) associated with immune checkpoint inhibitors (ICI).

MM shows heterogeneous clinical features and severity. Early recognition and immunosuppressive treatments may improve outcomes, but markers of rapid deterioration are lacking.

This nationwide retrospective study in Spain collected information on MM patients through March 2025 using a web-based structured questionnaire. Syndromes were centrally classified as definite, probable, or possible, and severity was assessed using Myasthenia Gravis Foundation of America (MGFA) classification.

We recruited 153 patients from 36 hospitals. Median age was 72 years [IQR 66–78] and 67% were male. By consensus definitions, 79 (52%) had definite/probable myositis, 14 (9%) definite/probable myasthenia, 57 (37%) fulfilled criteria for both disorders and 3 (2%) only possible myositis (excluded from analyses). At disease nadir 102/150 (68%) patients reached MGFA class III–V. Higher MGFA class correlated with elevated Troponin T (TnT, n=49, ρ=0.506, p=0.001) and CK (n=123, ρ=0.272, p=0.002), but not Troponin I (n=53, ρ=0.106, p=0.444). All patients discontinued ICI; 144/150 (96%) received immunosuppressants. At day +30, 108/150 (72%) had improved, 22 (15%) were unchanged and 20 (13%) had died. Patients who died early showed more frequently dyspnea (75% vs. 41%, p=0.007), palpitations (15% vs. 3%, p=0.050), dysphonia (65% vs. 45%, p=0.098), AChR-antibody positivity (65% vs. 28%, p=0.002) and concurrent myocarditis (76.5% vs. 46.5%, p=0.035), with higher TnT levels (1577 vs. 421 ng/L, p=0.013). In multivariable analysis, ventilatory support and AChR-positivity independently increased early mortality (OR=4.95; 95%CI 1.41-17.54, p=0.013 and OR=3.62; 95%CI 1.07-12.20, p=0.038 respectively).  

TnT and CK levels in the acute phase correlated with MGFA class, indicating potential as biomarkers of neuromuscular involvement and severity. Early mortality remains a major challenge, underscoring the need for timely management strategies.