001399 - Can Mepolizumab at asthma doses prevent the development of vasculitis in patients with EGPA?

Eosinophilic Granulomatosis with Polyangiitis (EGPA) presents with both ANCA-positive and ANCA-negative phenotypes, defined by their underlying pathogenic mechanisms. While asthma is often the initial feature, the ANCA-positive phenotype is characterized by necrotizing vasculitis. In this context, anti-IL-5 monoclonal antibodies, administered at 300 mg every 4 weeks, represent the cornerstone of treatment, controlling eosinophilia, improving respiratory function, and preventing systemic complications.

We report the case of a 64-year-old male with late-onset severe asthma corticosteroid-dependent and a high eosinophilic profile (peak 1500 cells/µL), treated with mepolizumab 100 mg every 4 weeks for the past 9 years, with significant improvement. In the last year, he experienced occasional exacerbations, prompting evaluation for antineutrophil cytoplasmic antibodies (ANCA). He also has nasal polyps, requiring surgical intervention. The patient has never reported systemic symptoms suggestive of vasculitis, either before or after initiating mepolizumab. Work-up included blood tests, urinalysis, renal function, and CT scans of the chest and paranasal sinuses.

After mepolizumab treatment, eosinophil counts decrease to zero FEV1 improved by 20% to 2.90 L (90% predicted), FVC 4.67 L (85.3%), FEV1/FVC 62%. Chest CT revealed peribronchial thickening and laminar atelectasis. Anti-MPO antibodies were positive (42.2 IU/mL), anti-PR3 negative. Echocardiogram was normal. Renal function and urinalysis were normal.

This case illustrates the delicate clinical boundary between severe asthma and early-stage EGPA. Despite late-onset asthma, nasal polyps, peripheral eosinophilia, and positive anti-MPO antibodies—features suggestive of  EGPA according de 2022 criteria of the European and American Societies of Reumatology —the patient has not developed systemic vasculitic manifestations. Notably, while receiving mepolizumab at 100 mg (below the 300 mg recommended for EGPA), he achieved marked improvement in respiratory symptoms, normalization of eosinophil counts, and a 20% recovery in FEV1, without systemic vasculitic complications. These findings highlight the protective role of anti-IL-5 therapy in controlling eosinophilic inflammation and potentially preventing progression to overt vasculitis, even at suboptimal dosing. They also underscore the importance of early recognition and targeted therapy in patients at the intersection of severe asthma and EGPA, where proactive management can mitigate systemic risk while addressing the respiratory phenotype.