Mepolizumab Reduces Hypereosinophilic Syndrome Flares Irrespective of Blood Eosinophil Count and Interleukin-5
Marc E Rothenberg, Florence Roufosse, Stanislas Faguer, Gerald J Gleich, Jonathan Steinfeld, Steven W Yancey, Eleni Mavropoulou, Namhee Kwon, HES Mepolizumab Study Group, Gabriel Ricardo García, Adriana Sosso, Luis Wehbe, Anahí Yañez, Daniël Blockmans, Florence Roufosse, Martti Anton Antila, Daniela Blanco, Sergio Grava, Marina Andrade Lima, Andreia Luisa Francisco Pez, Stanislas Faguer, Mohamed A Hamidou, Jean-Emmanuel Kahn, Guillaume Lefévre, Knut Brockow, Peter M Kern, Andreas J Reiter, Bastian Walz, Tobias Welte, Fabrizio Pane, Alessandro M Vannucchi, Ruth Cerino-Javier, Alfredo Gazca-Aguilar, Dante D Hernández-Colín, Héctor Glenn Valdéz-López, Izabela R Kupryś-Lipińska, Jacek Musial, Witold Prejzner, Eniko Mihaly, Viola Popov, Mihnea Tudor Zdrenghea, Sergey V Gritsaev, Vladimir Ivanov, Nikolay Tsyba, Aránzazu Alonso, Maria Cinta Cid Xutgla, Maria Laura Fox, Regina Garcia Delgado, Jesús María Hernández Rivas, Guillermo Sanz Santillana, Ana Isabel González, Andrew J Wardlaw, Praveen Akuthota, Joseph H Butterfield, Geoffrey L Chupp, John B Cox, Gerald J Gleich, Devi Jhaveri, Marc E Rothenberg, Marc E Rothenberg, Florence Roufosse, Stanislas Faguer, Gerald J Gleich, Jonathan Steinfeld, Steven W Yancey, Eleni Mavropoulou, Namhee Kwon, HES Mepolizumab Study Group, Gabriel Ricardo García, Adriana Sosso, Luis Wehbe, Anahí Yañez, Daniël Blockmans, Florence Roufosse, Martti Anton Antila, Daniela Blanco, Sergio Grava, Marina Andrade Lima, Andreia Luisa Francisco Pez, Stanislas Faguer, Mohamed A Hamidou, Jean-Emmanuel Kahn, Guillaume Lefévre, Knut Brockow, Peter M Kern, Andreas J Reiter, Bastian Walz, Tobias Welte, Fabrizio Pane, Alessandro M Vannucchi, Ruth Cerino-Javier, Alfredo Gazca-Aguilar, Dante D Hernández-Colín, Héctor Glenn Valdéz-López, Izabela R Kupryś-Lipińska, Jacek Musial, Witold Prejzner, Eniko Mihaly, Viola Popov, Mihnea Tudor Zdrenghea, Sergey V Gritsaev, Vladimir Ivanov, Nikolay Tsyba, Aránzazu Alonso, Maria Cinta Cid Xutgla, Maria Laura Fox, Regina Garcia Delgado, Jesús María Hernández Rivas, Guillermo Sanz Santillana, Ana Isabel González, Andrew J Wardlaw, Praveen Akuthota, Joseph H Butterfield, Geoffrey L Chupp, John B Cox, Gerald J Gleich, Devi Jhaveri, Marc E Rothenberg
Abstract
Background: Mepolizumab, an anti-interleukin-5 (IL-5) antibody, reduces disease flares in patients with hypereosinophilic syndrome (HES). Factors predicting treatment response are unknown.
Objective: To assess mepolizumab efficacy by baseline blood eosinophil count (BEC) and serum IL-5 level in patients with HES.
Methods: This post hoc analysis used data from the phase III study assessing mepolizumab in patients with HES (NCT02836496). Patients 12 years old or older, with HES for 6 or more months, 2 or more flares in the previous year, and BEC ≥1,000 cells/μL at screening were randomized (1:1) to 4-weekly subcutaneous mepolizumab (300 mg) or placebo, plus baseline HES therapy, for 32 weeks. The proportion of patients experiencing 1 or more flares (wk 32), annualized flare rate, and proportion of patients with change from baseline in Brief Fatigue Inventory (BFI) item 3 (wk 32), were analyzed by baseline BEC (<1500/≥1500 to <2500/≥2500 cells/μL). Flare outcomes were assessed by baseline serum IL-5 (<7.81/≥7.81 pg/mL).
Results: Across baseline BEC subgroups, mepolizumab reduced the proportion of patients experiencing 1 or more flares by 63% to 90% and flare rate by 58% to 84% (treatment-by-eosinophil interaction P = .76 and P = .90, respectively); patients had improved BFI item 3 score with mepolizumab versus placebo (cells/μL: <1,500: 54% vs 37%; ≥1,500 to <2,500: 47% vs 31%; ≥2,500: 61% vs 0%; treatment-by-eosinophil interaction P = .42). Most patients had undetectable baseline serum IL-5 levels; among these, mepolizumab versus placebo reduced the proportion of patients with 1 or more flares (77%) and flare rate (67%).
Conclusions: Mepolizumab was efficacious in the patients with HES studied, irrespective of baseline BEC. Undetectable IL-5 levels should not preclude mepolizumab treatment.
Keywords: Baseline blood eosinophil count; Fatigue; Flare; Hypereosinophilic syndrome; IL-5; Mepolizumab.
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
Source: PubMed