Baseline Demographics and Disease Characteristics of Patients with Hypereosinophilic Syndrome in a Placebo-Controlled Trial Evaluating the Steroid-Sparing Effects of the Anti-IL-5 Monoclonal Antibody, Mepolizumab.
Authors: Gleich Gerald J. , Schwartz Lawrence B. , Busse William W. , Huss-Marp Johannes , Walsh Scott R. 
Published: October 2019

Abstract
Mepolizumab is a humanized anti-IL-5 monoclonal antibody that blocks the actions of IL-5, the hematopoietin most responsible for eosinophil production, differentiation, and survival. Clinical experience in small numbers of patients with hypereosinophilic syndrome (HES), asthma, and atopic dermatitis indicated that intravenous (IV) mepolizumab therapy was associated with a reduction in blood eosinophils and was well-tolerated. A multicenter (26 sites worldwide), randomized, double-blind, placebo-controlled, and parallel-group trial has been conducted to evaluate the steroid-sparing effects of mepolizumab in patients with HES, and its efficacy and safety in controlling the signs and symptoms of this disease. The trial recruited patients 18–85 years of age with HES (blood eosinophil count >1500/μl for ≥6 months with evidence of eosinophilia-related organ involvement or dysfunction, without any known cause of eosinophilia), who tested negative for the FIP1L1-PDGFRα gene rearrangement and required 20–60 mg/day prednisone (monotherapy) to maintain blood eosinophils at <1000 cells/μL during a stabilization period of up to 6 weeks. The primary endpoint was the proportion of patients with disease control on ≤ 10 mg/day prednisone for ≥8 consecutive weeks during the 36-week treatment period. Here we report the baseline demographic and clinical characteristics of trial participants who comprise the largest HES population without the FIP1L1-PDGFRα mutation evaluated to date. Moreover, the clinical spectrum of HES in this population encompassed the multiple varieties of HES currently recognized. Of 107 patients screened, 85 were enrolled, 43 were randomized to mepolizumab (750 mg IV every 4 weeks), and 42 to placebo (saline IV every 4 weeks). No major differences in demographic and disease characteristics were observed between the treatment groups (Table). Many patients (60%) had previously tried and discontinued an HES therapy, notably imatinib mesylate (38%), interferon-α (21%), or hydroxyurea (21%). The most prevalent HES-related medical conditions at baseline were skin (47%) and respiratory (41%) disorders. The primary endpoint was significant in favor of mepolizumab treatment, thus providing evidence that this agent will offer clinical benefits in terms of steroid reduction/sparing in HES.
Patient demographics Placebo (n=42) Mepolizumab (n=43) Total (n=85) Age, y (mean±SD) 49.1±14.4 47.0±16.2 48.1±15.3 Men, % 17 (40%) 26 (60%) 43 (51%) Caucasian, % 34 (81%) 38 (88%) 72 (85%) Weight, kg (mean±SD) 79.7±18.3 80.9±22.2 80.3±20.3 BMI, kg/m2 (mean±SD) 27.8±5.8 27.0±6.4 27.4±6.1 Baseline prednisone≤30 mg, n (%) 30 (71%) 30 (70%) 60 (71%) Baseline prednisone >30 mg, n (%) 12 (29%) 13 (30%) 25 (29%) Previously treated for HES, n (%) 40 (95%) 41 (95%) 81 (95%) HES duration, y (mean±SD) 6.5±9.5 4.3±5.6 5.4±7.8 Age at HES onset, y (mean±SD) 42.7±16.2 42.7±17.7 42.7±16.9