PO:35:223 | Biologic therapy for sustained remission in eosinophilic myocarditis: real-world evidence from a tertiary center experience

Federica Davanzo¹, Caterina Menghi², Andrea Silvio Giordani², Anna Baritussio², Federico Scognamiglio², Cristina Vicenzetto², Luca Iorio¹, Renzo Marcolongo², Cristina Basso³, Andrea Doria¹, Roberto Padoan¹, Alida Linda Patr Caforio² | ¹Rheumatology Unit, Department of Medicine, University of Padua Padova, Italy; ²Cardiology Unit, Department of Cardiac, Vascular, Thoracic Sciences and Public Health, University of Padua Padova, Italy; ³Cardiovascular Pathology, Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padua Padova, Italy

Aim of the Study: To characterize clinical, laboratory, and diagnostic features of eosinophilic myocarditis (EM) patients treated with monoclonal antibodies (mAbs) targeting interleukin (IL)-5/5R (mepolizumab or benralizumab) or IL-4/13 (dupilumab) and to assess effectiveness and safety of mAbs in EM.

Methods. We retrospectively enrolled patients with EM actively followed up at a single tertiary care center, who received anti-IL-5/5R or anti-IL-4/13 biologics as part of maintenance therapy following induction with high-dose corticosteroids, with or without additional immunosuppressive agents.

Results. A total of 19 patients with EM were enrolled. The mean age at diagnosis was 49.6 ± 20.5 years, with a male predominance (63.2 %). Of the 19 patients with EM, 17 (89%) had a concomitant diagnosis of EGPA (2 HES, 15 EGPA), with EM being the initial clinical manifestation in 73.7% of these cases. Pseudo-infarction was the predominant manifestation (68.4%), followed by heart failure (26.3%) and fulminant myocarditis (15.8%). Endomyocardial biopsy was performed in 36.8%, but prior steroid treatment prevented histological confirmation of eosinophilic infiltrates in two of these cases. Troponin and C-reactive protein were elevated at diagnosis; peripheral eosinophilia was present in 89%. Autoantibody testing revealed anti-heart autoantibody (AHA) in 31.6% and anti-intercalated disks autoantibodies (AIDA) in 10.5%, while only 1 (5.26%) patient tested positive for ANCA. Echocardiography showed overall reduced left ventricular ejection fraction (LVEF) (48.2±14%), with pericardial effusion (31.6%) and intracavitary thrombus (31.6%), reflecting severe myocardial involvement and need for anticoagulation. Cardiac magnetic resonance (CMR) revealed myocardial edema in 57.9% and late gadolinium enhancement (LGE) in all cases (89.5% subendocardial). As induction treatment, 94.7% of patients (18/19) received high-dose corticosteroids and 52.6% (10/19) were also treated with DMARDs, including 4 patients (21.1%) with rituximab and 6 (31.6%) with conventional DMARDs. Intravenous immunoglobulins were administered in combination in 3 patients (15.8%). As maintenance therapy, patients received mepolizumab (300mg/4w, n=16), benralizumab (30 mg/8w, n=2), and dupilumab (300 mg/2w, n=1), after 14 (1-50) months from diagnosis. At 50±39 months, 84.21% achieved significant functional improvement (NYHA class I), with LVEF increasing to 55.6±8.2%. Peripheral eosinophilia decreased significantly (p<0.001). CMR showed persistent LGE in all patients, though with reduced extent in 50%. No myocarditis relapses occurred, and none withdrew from therapy due to side effects. All patients except one were able to discontinue systemic steroids, and DMARDs were maintained as concomitant treatment in only 30% (3/10) of patients who had received DMARDs during induction.

Conclusions. Biologic agents targeting IL-5/5R and IL-4/13 pathways appear effective and safe in maintaining long-term remission in EM, allowing corticosteroid withdrawal and sustained clinical improvement. These findings support their role as a steroid-sparing strategy in both isolated EM and EGPA-associated cases.