Time-dependent effects of interleukin-1 blockade by anakinra in myocarditis and inflammatory cardiomyopathy

Aims: Interleukin-1 (IL-1) plays a central role in myocardial inflammation and adverse remodelling. However, the long-term clinical impact of IL-1 blockade in myocarditis and inflammatory cardiomyopathy (Infl-CMP), particularly according to treatment exposure and discontinuation, remains unclear. We evaluated time-dependent outcomes in patients treated with the IL-1 receptor antagonist anakinra. Methods and results: We included 42 consecutive patients with definite myocarditis or Infl-CMP diagnosed by cardiac magnetic resonance either with or without endomyocardial biopsy. Mean age was 46 ± 17 years, 60% were male, and mean left ventricular ejection fraction (LVEF) at presentation was 43 ± 16%. Patients received anakinra (100 mg/day) for a median of 11 months and were followed for 51 ± 20 months. The primary endpoint was major adverse events (MAE), defined as cardiac death, heart transplantation, major ventricular arrhythmias, hospitalization for acute heart failure, or recurrent myocarditis. Time-updated Kaplan-Meier analysis showed a significant reduction in MAE during anakinra treatment compared with both pre-treatment and post-discontinuation phases (log-rank P < .001). Events were rare during active treatment, whereas most deaths (7/8) and all major ventricular arrhythmias occurred outside the treatment phase. Recurrent myocarditis was reduced during therapy (1/42 vs 9/32 pre-treatment; P = .002) and reappeared after discontinuation (3/37). Cardiac-related hospitalizations decreased during treatment and increased thereafter. These changes were paralleled by improvements in troponin, LVEF (≥5% in one-third), cardiac magnetic resonance inflammatory abnormalities, and arrhythmic burden. Outcomes differed according to aetiology. Conclusion: Anakinra was associated with a marked reduction in MAE during active treatment, with re-emergence after discontinuation, supporting a potential role for sustained IL-1 blockade in selected high-risk patients.