Mepolizumab as a corticosteroid-sparing agent in lymphocytic variant hypereosinophilic syndrome

Abstract

Background-Mepolizumab, a monoclonal anti-interleukin-5 (IL-5) antibody, is an effective corticosteroid-sparing agent for patients with F/P-negative hypereosinophilic syndrome. Lymphocytic variant hypereosinophilic syndrome (L-HES) is characterized by marked overproduction of IL-5 by dysregulated T-cells.

Episodic angioedema with eosinophilia (Gleich syndrome) is a multilineage cell cycling disorder

“…T-cell clonality was determined in peripheral blood by PCR of T-cell receptor (TCR)-γ rearrangement patterns. 15 Additional studies to assess end organ involvement were performed as clinically indicated.…”

“…Serum CCL17/TARC (R&D) and total serum tryptase were quantified as previously described. 15,16 Stem cell factor (SCF) was assessed by an enzyme-linked immunosorbent assay according to the manufacturer's (R&D) instructions; the limit of detection was 9 pg/mL. Total serum IgE levels were determined by ImmunoCAP (Phadia).…”

Mucosal Eosinophils

“…In addition to its robust circulating eosinophil reduction capacity, anti-IL-5 antibody also demonstrated ex vivo efficacy (Stein et al, 2008). The anti-IL-5 therapy proved to be effective in controlling hypereosinophilic syndrome in terms of eosinophil count reduction and steroid sparing Roufosse et al, 2010;Garrett et al, 2004). Furthermore, anti-IL-5 therapy also demonstrated promising effectiveness in reducing tissue eosinophilia in eosinophilic esophagitis (EoE) (Assa'ad et al, 2011;Spergel et al, 2012), a type of eosinophilic disorder in the upper GI tract.…”

Clinical management of the hypereosinophilic syndromes

“…Furthermore, almost half of the patients receiving mepolizumab were durably tapered off CS until the end of the study. Exploratory investigations conducted during this trial identified a subset of patients with L-HES, and their response to IL-5-targeted therapy was compared with that of patients with normal T-cell phenotyping studies [66]. Mepolizumab showed similar efficacy in both groups in terms of CS-sparing, although a lower proportion of patients with L-HES maintained eosinophil levels below 600/µl throughout the study.…”