Use of the Il-1 Inhibitor (Anakinra) for the Treatment of Acute Myocarditis in Pediatric Patients: A Single-Center Experience

Abstract

Objectives Myocarditis is an acute inflammatory process of the myocardium characterized by impaired contractile function. The incidence is 1-2 cases/100,000 children, but it has increased since 2020 due to Pediatric Multisystem Inflammatory Syndrome (MIS-C). The pathogenesis involves an inflammatory process mediated by IL-1. Treatment remains heterogeneous: in addition to hemodynamic support, IVIG and corticosteroids (CS) are well-established treatments, although modalities are not standardized. Anakinra, an IL-1 receptor antagonist, could be useful in modulating the inflammatory response and improving cardiac function in the acute phase.[1,2] To describe the clinical course and treatment in pediatric patients with acute myocarditis, isolated or associated with MIS-C, admitted to our Hospital (Ospedale Maggiore Policlinico, Milan IT) between 2020 and July 2025. Methods A single-center, retrospective, observational study. Inclusion criteria: age <18 years, diagnosis of myocarditis according to ESC guidelines. Exclusion criteria: chronic or pre-existing heart diseases. Patients were divided into 2 groups based on the therapy implemented, comparing clinical characteristics and cardiac function outcome (ejection fraction and time to normalization): Group A: patients treated with maximal therapy (high-dose steroid+IVIG+Anakinra). Group B: patients treated with IVIG ± systemic steroid. Results 24 patients (median age 10; IQR 7.3-13.3) were identified, presenting with global myocarditis (13/24) or focal myocarditis (11/24), 8 females. 13 patients had MIS-C, and 11 had isolated myocarditis. - 3 patients with focal myocarditis did not receive anti-inflammatory therapy. - 9/21 Group A. In these patients, the median Ejection Fraction (EF) at the start of treatment was 45%, with normalization achieved in 5.3 days. 2/9 (22%) had a preserved EF at the start of treatment, with high inflammatory markers. - 12/21 Group B: 9/12 received IVIG + CS, 2/12 IVIG only, and 1/12 CS only. The median EF at the start of treatment was 50% (normal in 6/12), normalizing in 6.6 days. The death of an 11-day-old neonate (weight 3.3 kg), with viral myocarditis without associated comorbidities and treated with IVIG only, was recorded in this group. Conclusion Despite the limitations related to the sample size and the retrospective nature of the study, the data suggest that early and more aggressive immunomodulatory treatment may contribute to a faster recovery of contractile function and improve outcomes. Treatment with Anakinra could represent a valid therapeutic option for optimizing anti-inflammatory therapy in the acute phase. No adverse events were observed in patients treated with IV Anakinra (5-10 mg/kg/day). Further controlled prospective studies will be necessary to confirm the observed data References [1.] Goldberg JA. Curr Opin Cardiol 2024;39:315-22. [2.] Licciardi F. Front Pediatr 2025;13:1544126.