Efficacy and safety of monoclonal antibodies targeting interleukin-5 and interleukin-4/13 pathways in eosinophilic myocarditis: a single-center experience

Abstract Background Eosinophilic myocarditis (EM) is a rare, life-threatening inflammatory heart disease with diverse clinical manifestations, often associated with systemic eosinophilic syndromes such as eosinophilic granulomatosis with polyangiitis (EGPA). While monoclonal antibodies (mAbs) targeting interleukin (IL)-5/5R or IL-4/13 have proven effective in controlling systemic eosinophilic manifestations, their effectiveness and safety in EM remain unexplored. Purpose 1) To characterize clinical, laboratory, and diagnostic features of a highly selected cohort of patients with EM who received anti-IL-5/5R (mepolizumab or benralizumab) or anti-IL-4/13 (dupilumab) therapy; 2) to assess effectiveness and safety of mAbs in severe forms of EM. Methods We retrospectively enrolled patients with EM actively followed up at a single tertiary care center, with or without a prior or concurrent diagnosis of EGPA, who received anti-IL-5/5R or anti-IL-4/13 therapy. Results 13 patients with EM received anti-IL-5/5R or anti-IL-4/13 agents: mepolizumab (300 mg/4 weeks, n=10), benralizumab (30 mg/8 weeks, n=2), and dupilumab (300 mg/2 weeks, n=1). Mean age at diagnosis was 48±18 years, with a male predominance (52%). EGPA was the most frequent underlying condition (85%), with myocarditis as its initial presentation in 64%. Pseudo-infarction was the predominant manifestation (46%), followed by heart failure (38%). Fulminant myocarditis occurred in 16%. Endomyocardial biopsy was performed in 62%, but prior steroid treatment prevented histological confirmation of eosinophilic infiltrates in two cases. Troponin and C-reactive protein were elevated at diagnosis; peripheral eosinophilia was present in 92%. Autoantibody testing revealed anti-heart autoantibodies (AHA) in 50% and anti-intercalated disks autoantibodies (AIDA) in 33%, while antineutrophil cytoplasmic antibodies (ANCA) were negative in all patients. Echocardiography showed overall reduced left ventricular ejection fraction (LVEF) (46 ± 12%), with pericardial effusion (42%) and intracavitary thrombus (46%), reflecting severe myocardial involvement and need for anticoagulation. Cardiac magnetic resonance (CMR) revealed myocardial edema in 82% and late gadolinium enhancement (LGE) in all cases (82% subendocardial). At 54±34 months, 77% achieved significant functional improvement (NYHA class I), with LVEF increasing to 53±11%. Peripheral eosinophilia decreased significantly (p0.001). CMR showed persistent LGE in all patients, though with reduced extent in 50%. All but one had discontinued steroids at last follow-up. No relapses occured, and none withdrew from therapy due to side effects. Conclusions This study provides the first systematic evaluation of mAbs in EM. Our findings suggest that anti-IL-5/5R and anti-IL-4/13 agents are effective even in severe cases of EM, whether isolated or as a manifestation of EGPA. mAbs offer a safe alternative to reduce corticosteroid dependence, while improving outcomes.