Mepolizumab Reduces Hypereosinophilic Syndrome Flares Irrespective of Blood Eosinophil Count and Interleukin-5.
Baseline blood eosinophil count
Fatigue
Flare
Hypereosinophilic syndrome
IL-5
Mepolizumab
Journal
The journal of allergy and clinical immunology. In practice
ISSN: 2213-2201
Titre abrégé: J Allergy Clin Immunol Pract
Pays: United States
ID NLM: 101597220
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
received:
09
11
2021
revised:
14
04
2022
accepted:
29
04
2022
pubmed:
15
5
2022
medline:
14
9
2022
entrez:
14
5
2022
Statut:
ppublish
Résumé
Mepolizumab, an anti-interleukin-5 (IL-5) antibody, reduces disease flares in patients with hypereosinophilic syndrome (HES). Factors predicting treatment response are unknown. To assess mepolizumab efficacy by baseline blood eosinophil count (BEC) and serum IL-5 level in patients with HES. 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). 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%). Mepolizumab was efficacious in the patients with HES studied, irrespective of baseline BEC. Undetectable IL-5 levels should not preclude mepolizumab treatment.
Sections du résumé
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.
Identifiants
pubmed: 35568330
pii: S2213-2198(22)00482-2
doi: 10.1016/j.jaip.2022.04.037
pii:
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Interleukin-5
0
mepolizumab
90Z2UF0E52
Banques de données
ClinicalTrials.gov
['NCT02836496']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2367-2374.e3Investigateurs
Gabriel Ricardo García
(GR)
Adriana Sosso
(A)
Luis Wehbe
(L)
Anahí Yañez
(A)
Daniël Blockmans
(D)
Florence Roufosse
(F)
Martti Anton Antila
(MA)
Daniela Blanco
(D)
Sergio Grava
(S)
Marina Andrade Lima
(MA)
Andreia Luisa Francisco Pez
(AL)
Stanislas Faguer
(S)
Mohamed A Hamidou
(MA)
Jean-Emmanuel Kahn
(JE)
Guillaume Lefévre
(G)
Knut Brockow
(K)
Peter M Kern
(PM)
Andreas J Reiter
(AJ)
Bastian Walz
(B)
Tobias Welte
(T)
Fabrizio Pane
(F)
Alessandro M Vannucchi
(AM)
Ruth Cerino-Javier
(R)
Alfredo Gazca-Aguilar
(A)
Dante D Hernández-Colín
(DD)
Héctor Glenn Valdéz-López
(HG)
Izabela R Kupryś-Lipińska
(IR)
Jacek Musial
(J)
Witold Prejzner
(W)
Eniko Mihaly
(E)
Viola Popov
(V)
Mihnea Tudor Zdrenghea
(MT)
Sergey V Gritsaev
(SV)
Vladimir Ivanov
(V)
Nikolay Tsyba
(N)
Aránzazu Alonso
(A)
Maria Cinta Cid Xutgla
(MC)
Maria Laura Fox
(ML)
Regina Garcia Delgado
(RG)
Jesús María Hernández Rivas
(JM)
Guillermo Sanz Santillana
(GS)
Ana Isabel González
(AI)
Andrew J Wardlaw
(AJ)
Praveen Akuthota
(P)
Joseph H Butterfield
(JH)
Geoffrey L Chupp
(GL)
John B Cox
(JB)
Gerald J Gleich
(GJ)
Devi Jhaveri
(D)
Marc E Rothenberg
(ME)
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.