Mepolizumab incompletely suppresses clinical flares in a pilot study of episodic angioedema with eosinophilia

Abstract

BackgroundEpisodic angioedema with eosinophilia (EAE) is a rare multilineage cyclic syndrome of unknown etiology characterized by episodes of angioedema, myalgia, fatigue, and fever that occur every 3-8 weeks and resolve between episodes without therapy. Cyclic elevations in serum interleukin-5 (IL-5) levels and neutrophils precede the increase in absolute eosinophil count (AEC) in most patients. ObjectiveTo assess the role of IL-5-driven eosinophilia in the clinical manifestations of EAE MethodsAn open-label pilot study of mepolizumab (700 mg intravenously monthly for 3 months followed by sequential dose reduction to the FDA-approved dose of 300 mg subcutaneously monthly) was conducted. The primary endpoint was reduction in the number and severity of clinical symptoms as assessed by patient-reported symptom questionnaires. Secondary endpoints were ≥75% reduction in peak AEC after one dose of mepolizumab and sustained reduction in AEC after 3 doses of mepolizumab. Exploratory endpoints included effects of mepolizumab treatment on other cell lineages (numbers and surface marker expression), levels of plasma mediators, and biomarkers of eosinophil activation. ResultsFour female and one male (median age 45) participants with EAE were enrolled. None of the 5 participants experienced a reduction in the number of symptomatic flares on mepolizumab therapy, and 1 participant withdrew prior to study completion due to lack of improvement. Peak AEC was reduced by ≥75% in 3 participants after the first dose of mepolizumab and in 4 participants after 3 doses. ConclusionsIn a small cohort of participants with EAE, mepolizumab was unsuccessful in substantially reducing clinical symptoms despite reduction in AEC.