Safety and Efficacy of Mepolizumab in Hypereosinophilic Syndrome: An Open-Label Extension Study.
Anti-IL-5
Efficacy
Flare
Hypereosinophilic syndrome
Mepolizumab
Oral corticosteroid
Safety
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:
12 2021
12 2021
Historique:
received:
25
05
2021
revised:
12
07
2021
accepted:
23
07
2021
pubmed:
15
8
2021
medline:
30
12
2021
entrez:
14
8
2021
Statut:
ppublish
Résumé
A double-blind, placebo-controlled, phase III study (200622) showed that mepolizumab reduces disease flares for patients with uncontrolled FIP1-like-1-platelet-derived growth factor receptor α-negative hypereosinophilic syndrome (HES) and two or more flares in the previous year. To further characterize the safety, clinical benefit, and pharmacodynamics of mepolizumab. Eligible patients from both treatment arms of the double-blind study could enter an open-label extension study (205203; NCT03306043) to receive 4-weekly mepolizumab (300 mg subcutaneously) plus background therapy for 20 weeks. Primary end points were safety-based; other end points included flare rates and changes from baseline in mean daily oral corticosteroid (OCS) dose and blood eosinophil count. Of 104 patients who completed the double-blind study, 98% (previous placebo, n = 52; previous mepolizumab, n = 50) enrolled in the open-label extension. Overall, 66 of patients reported adverse events (AEs) (65%), 15 reported treatment-related AEs (15%), and nine reported serious AEs (9%). No events were fatal. The annualized flare rate (95% confidence interval) in the previous placebo and previous mepolizumab groups was 0.37 (0.16-0.86) and 0.14 (0.04-0.49) events/y, respectively. Of 72 patients receiving OCS during weeks 0 to 4, 20 (28%; previous placebo, n = 14; previous mepolizumab, n = 6) achieved 50% or greater reductions in mean daily dose during weeks 16 to 20. At week 20, blood eosinophil count was reduced by 89% in patients previously receiving placebo and remained reduced for those previously receiving mepolizumab. Extended mepolizumab treatment was associated with a positive benefit-risk profile. Continued control of disease flares and blood eosinophil counts, plus reductions in OCS use, were observed with mepolizumab in patients with FIP1-like-1-platelet-derived growth factor receptor α-negative HES.
Sections du résumé
BACKGROUND
A double-blind, placebo-controlled, phase III study (200622) showed that mepolizumab reduces disease flares for patients with uncontrolled FIP1-like-1-platelet-derived growth factor receptor α-negative hypereosinophilic syndrome (HES) and two or more flares in the previous year.
OBJECTIVE
To further characterize the safety, clinical benefit, and pharmacodynamics of mepolizumab.
METHODS
Eligible patients from both treatment arms of the double-blind study could enter an open-label extension study (205203; NCT03306043) to receive 4-weekly mepolizumab (300 mg subcutaneously) plus background therapy for 20 weeks. Primary end points were safety-based; other end points included flare rates and changes from baseline in mean daily oral corticosteroid (OCS) dose and blood eosinophil count.
RESULTS
Of 104 patients who completed the double-blind study, 98% (previous placebo, n = 52; previous mepolizumab, n = 50) enrolled in the open-label extension. Overall, 66 of patients reported adverse events (AEs) (65%), 15 reported treatment-related AEs (15%), and nine reported serious AEs (9%). No events were fatal. The annualized flare rate (95% confidence interval) in the previous placebo and previous mepolizumab groups was 0.37 (0.16-0.86) and 0.14 (0.04-0.49) events/y, respectively. Of 72 patients receiving OCS during weeks 0 to 4, 20 (28%; previous placebo, n = 14; previous mepolizumab, n = 6) achieved 50% or greater reductions in mean daily dose during weeks 16 to 20. At week 20, blood eosinophil count was reduced by 89% in patients previously receiving placebo and remained reduced for those previously receiving mepolizumab.
CONCLUSIONS
Extended mepolizumab treatment was associated with a positive benefit-risk profile. Continued control of disease flares and blood eosinophil counts, plus reductions in OCS use, were observed with mepolizumab in patients with FIP1-like-1-platelet-derived growth factor receptor α-negative HES.
Identifiants
pubmed: 34389506
pii: S2213-2198(21)00891-6
doi: 10.1016/j.jaip.2021.07.050
pii:
doi:
Substances chimiques
Adrenal Cortex Hormones
0
Antibodies, Monoclonal, Humanized
0
mepolizumab
90Z2UF0E52
Banques de données
ClinicalTrials.gov
['NCT03306043', 'NCT02836496']
Types de publication
Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4431-4440.e1Investigateurs
Gabriel Ricardo García
(GR)
Pablo Pascale
(P)
Luis Wehbe
(L)
Daniël Blockmans
(D)
Florence Roufosse
(F)
Martti Anton Antila
(MA)
Daniela Blanco
(D)
Andreia Luisa Francisco Pez
(AL)
Stanislas Faguer
(S)
Jean-Emmanuel Kahn
(JE)
Guillaume Lefévre
(G)
Antoine Neel
(A)
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)
Dante D Hernández-Colín
(DD)
Héctor Glenn Valdéz-López
(HG)
Izabela R Kupryś-Lipińska
(IR)
Jacek Musial
(J)
Eniko Mihaly
(E)
Viola Maria Popov
(VM)
Vladimir Ivanov
(V)
Nikolay Tsyba
(N)
Maria C Cid
(MC)
Maria Laura Fox
(ML)
Guillermo Sanz Santillana
(GS)
Andrew J Wardlaw
(AJ)
Praveen Akuthota
(P)
Joseph H Butterfield
(JH)
Geoffrey L Chupp
(GL)
Gerald J Gleich
(GJ)
Devi Jhaveri
(D)
Marc E Rothenberg
(ME)
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.