Onset of effect and impact on health-related quality of life, exacerbation rate, lung function, and nasal polyposis symptoms for patients with severe eosinophilic asthma treated with benralizumab (ANDHI): a randomised, controlled, phase 3b trial.
Journal
The Lancet. Respiratory medicine
ISSN: 2213-2619
Titre abrégé: Lancet Respir Med
Pays: England
ID NLM: 101605555
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
04
06
2020
revised:
18
08
2020
accepted:
25
08
2020
pubmed:
29
12
2020
medline:
18
3
2021
entrez:
28
12
2020
Statut:
ppublish
Résumé
ANDHI was done to assess the efficacy of benralizumab, including onset of effect and impact on health-related quality of life (HRQOL), exacerbation rate, lung function, and nasal polyposis symptoms. This phase 3b, randomised, double-blind, parallel-group, placebo-controlled ANDHI study was completed in adults (aged 18-75 years) with severe eosinophilic asthma with at least 2 exacerbations in the previous year, despite high-dose inhaled corticosteroid plus additional controllers, screening blood eosinophil counts of at least 150 cells per μL, and an Asthma Control Questionnaire 6 (ACQ-6) score of 1·5 or more. Patients who met eligibility criteria were randomly assigned (2:1; stratified by previous exacerbation count [two, or three or more], maintenance oral corticosteroid use, and region), using an integrated web-based response system, to receive benralizumab at 30 mg every 8 weeks (first three doses given 4 weeks apart) or matched placebo for 24 weeks. Primary efficacy measure was annualised asthma exacerbation rate, with rate ratio (RR) calculated over the approximate 24-week follow-up. Secondary efficacy measures included change from baseline to end of treatment (week 24) in St George's Respiratory Questionnaire (SGRQ) total score (key secondary endpoint), FEV Between July 7, 2017, and Sept 25, 2019, 656 patients received benralizumab (n=427) or placebo (n=229). Baseline characteristics were consistent with severe eosinophilic asthma. Benralizumab significantly reduced exacerbation risk by 49% compared with placebo (RR estimate 0·51, 95% CI 0·39-0·65; p<0·0001) over the 24-week treatment period and provided clinically meaningful and statistically significant improvement from baseline to week 24 in SGRQ total score versus placebo (least squares mean change from baseline -8·11 (95% CI -11·41 to -4·82; p<0·0001), with similar differences at earlier timepoints. Benralizumab improved FEV Our results extend the efficacy profile of benralizumab for patients with severe eosinophilic asthma, showing early clinical benefits in patient-reported outcomes, HRQOL, lung function, and nasal polyposis symptoms. AstraZeneca.
Sections du résumé
BACKGROUND
ANDHI was done to assess the efficacy of benralizumab, including onset of effect and impact on health-related quality of life (HRQOL), exacerbation rate, lung function, and nasal polyposis symptoms.
METHODS
This phase 3b, randomised, double-blind, parallel-group, placebo-controlled ANDHI study was completed in adults (aged 18-75 years) with severe eosinophilic asthma with at least 2 exacerbations in the previous year, despite high-dose inhaled corticosteroid plus additional controllers, screening blood eosinophil counts of at least 150 cells per μL, and an Asthma Control Questionnaire 6 (ACQ-6) score of 1·5 or more. Patients who met eligibility criteria were randomly assigned (2:1; stratified by previous exacerbation count [two, or three or more], maintenance oral corticosteroid use, and region), using an integrated web-based response system, to receive benralizumab at 30 mg every 8 weeks (first three doses given 4 weeks apart) or matched placebo for 24 weeks. Primary efficacy measure was annualised asthma exacerbation rate, with rate ratio (RR) calculated over the approximate 24-week follow-up. Secondary efficacy measures included change from baseline to end of treatment (week 24) in St George's Respiratory Questionnaire (SGRQ) total score (key secondary endpoint), FEV
FINDINGS
Between July 7, 2017, and Sept 25, 2019, 656 patients received benralizumab (n=427) or placebo (n=229). Baseline characteristics were consistent with severe eosinophilic asthma. Benralizumab significantly reduced exacerbation risk by 49% compared with placebo (RR estimate 0·51, 95% CI 0·39-0·65; p<0·0001) over the 24-week treatment period and provided clinically meaningful and statistically significant improvement from baseline to week 24 in SGRQ total score versus placebo (least squares mean change from baseline -8·11 (95% CI -11·41 to -4·82; p<0·0001), with similar differences at earlier timepoints. Benralizumab improved FEV
INTERPRETATION
Our results extend the efficacy profile of benralizumab for patients with severe eosinophilic asthma, showing early clinical benefits in patient-reported outcomes, HRQOL, lung function, and nasal polyposis symptoms.
FUNDING
AstraZeneca.
Identifiants
pubmed: 33357499
pii: S2213-2600(20)30414-8
doi: 10.1016/S2213-2600(20)30414-8
pii:
doi:
Substances chimiques
Anti-Asthmatic Agents
0
Antibodies, Monoclonal, Humanized
0
benralizumab
71492GE1FX
Banques de données
ClinicalTrials.gov
['NCT03170271']
Types de publication
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
260-274Investigateurs
Wolfgang Pohl
(W)
Robert Voves
(R)
Maud Deschampheleire
(M)
Renaud Louis
(R)
Jean-Benoit Martinot
(JB)
Rudi Peché
(R)
Kenneth Chapman
(K)
Amarjit Cheema
(A)
Delbert Dorscheid
(D)
J Mark FitzGerald
(JM)
Remi Gagnon
(R)
William Patrick Killorn
(WP)
Ronald Olivenstein
(R)
George Philteos
(G)
Clare Ramsey
(C)
J Douglass Rolf
(JD)
Brandie Walker
(B)
Ole Hilberg
(O)
Tina Skjold
(T)
Ingrid Titlestad
(I)
Auli Hakulinen
(A)
Maritta Kilpeläinen
(M)
Michèle Ben Hayoun
(M)
Philippe Bonniaud
(P)
Arnaud Bourdin
(A)
Pascal Chanez
(P)
Frédéric De Blay
(F)
Gaëtan Deslee
(G)
Gilles Devouassoux
(G)
Alain Didier
(A)
Youcef Douadi
(Y)
Stéphanie Fry
(S)
Gilles Garcia
(G)
Pierre-Olivier Girodet
(PO)
Christophe Leroyer
(C)
Antoine Magnan
(A)
Guillaume Mahay
(G)
Cécilia Nocent
(C)
Christophe Pison
(C)
Pauline-Marie Roux
(PM)
Camille Taillé
(C)
Juliana-Angelica Tiotiu
(JA)
Ekkehard Beck
(E)
Margret Jandl
(M)
Christian Kaehler
(C)
Frank Kässner
(F)
Frank Koesters
(F)
Juliane Kronsbein
(J)
Thomas Schaum
(T)
Christian Schulz
(C)
Dirk Skowasch
(D)
Christian Taube
(C)
Tobias Welte
(T)
Andrés de Roux
(A)
Bianca Beghé
(B)
Francesco Blasi
(F)
Giorgio Walter Canonica
(GW)
Giovanna Carpagnano
(G)
Cristiano Caruso
(C)
Angelo Guido Corsico
(AG)
Elio Constantino
(E)
Nunzio Crimi
(N)
Piero Maestrelli
(P)
Francesco Menzella
(F)
Manlio Milanese
(M)
Alberto Papi
(A)
Girolamo Pelaia
(G)
Laura Pini
(L)
Pierachille Santus
(P)
Eleonora Savi
(E)
Nicola Scichilone
(N)
Gianenrico Senna
(G)
Giuseppe Spadaro
(G)
Adriano Vaghi
(A)
Steven Gans
(S)
Jurgen Hölters
(J)
B Langeveld
(B)
Willem Pieters
(W)
G H A Staaks
(GHA)
Ilonka van Veen
(I)
J W K van den Berg
(JWK)
Gunnar Einvik
(G)
Sverre Lehmann
(S)
Ismael Ali García
(I)
Carlos Almonacid
(C)
Irina Bobolea
(I)
Paloma Campo Mozo
(P)
Gustavo de Luiz
(G)
Christian Domingo Ribas
(C)
José María Echave-Sustaeta María-Tomé
(JM)
Juan Luis García Rivero
(JL)
Borja García-Cosío Piqueras
(B)
Ana Gómez-Bastero Fernández
(A)
Ruperto González Pérez
(R)
Aythamy Henríquez Santa
(A)
Carlos Martínez Rivera
(C)
Xavier Muñoz Gall
(X)
Jacinto Ramos
(J)
Jose Gregorio Soto Campos
(J)
Carmen Vidal Pan
(C)
Nikolai Stenfors
(N)
Alf Tunsäter
(A)
Ines Vinge
(I)
Rekha Chaudhuri
(R)
Timothy Harrison
(T)
Adel Mansur
(A)
Shuaib Nasser
(S)
Monica Nordstrom
(M)
Paul Pfeffer
(P)
Dinesh Saralaya
(D)
Philip Short
(P)
Arun Adlakha
(A)
Oral Alpan
(O)
Francis Averill
(F)
Anil Badhwar
(A)
Jose Bardelas
(J)
Barbara Baxter
(B)
George Bensch
(G)
William Berger
(W)
Jonathan Bernstein
(J)
Tracy Bridges
(T)
Ryan Brimeyer
(R)
William Calhoun
(W)
Edward Campbell
(E)
William Brett Cherry
(WB)
Geoffrey Chupp
(G)
Lee Clore
(L)
John Cohn
(J)
Jeremy Cole
(J)
John Condemi
(J)
James Cury
(J)
Benjamin Davis
(B)
Samuel DeLeon
(S)
Luis Delacruz
(L)
Joseph Diaz
(J)
David Erb
(D)
Emeka Eziri
(E)
Faisal Fakih
(F)
Douglas Fiedler
(D)
David Fost
(D)
Stephen Fritz
(S)
Erika Gonzalez
(E)
Brad Goodman
(B)
Peter Gottlieb
(P)
Gregory Gottschlich
(G)
Richard Gower
(R)
Rizan Hajal
(R)
James Harris
(J)
Hengameh Heidarian-Raissy
(H)
Albrecht Heyder
(A)
David Hill
(D)
Fernando Holguin
(F)
Iftikhar Hussain
(I)
Jonathan Illowite
(J)
Joshua Jacobs
(J)
Mikell Jarratt
(M)
Harold Kaiser
(H)
Neil Kao
(N)
Ravindra Kashyap
(R)
David Kaufman
(D)
Edward Kent
(E)
Kenneth Kim
(K)
Ryan Klein
(R)
Monica Kraft
(M)
Ritsu Kono
(R)
Shahrukh Kureishy
(S)
Jeffrey Leflein
(J)
Mila Leong
(M)
Huamin Li
(H)
Robert Lin
(R)
Njira Lugogo
(N)
Michael Marcus
(M)
Diego Jose Maselli Caceres
(DJ)
Vinay Mehta
(V)
Curtis Mello
(C)
Mark Millard
(M)
Aaron Milstone
(A)
Arjun Mohan
(A)
Wendy Moore
(W)
Mark Moss
(M)
Nayla Mumneh
(N)
Thomas O'Brien
(T)
David Ostransky
(D)
Michael Palumbo
(M)
Purvi Parikh
(P)
Sudhir Parikh
(S)
Amit Patel
(A)
Guido Perez
(G)
Warren Pleskow
(W)
Bruce Prenner
(B)
Dileep Puppala
(D)
John Ramey
(J)
Joan Reibman
(J)
Ramon Reyes
(R)
Emory Robinette
(E)
Ileana Rodicio
(I)
Stephen Ryan
(S)
Sudhir Sekhsaria
(S)
Barry Sigal
(B)
Vinay Sikand
(V)
Weily Soong
(W)
Selwyn Spangenthal
(S)
Roy St John
(R)
Gary Steven
(G)
Vijay Subramaniam
(V)
Kaharu Sumino
(K)
Eric Sztejman
(E)
Ricardo A Tan
(RA)
Tonny Tanus
(T)
Charles Thompson
(C)
Carl Thornblade
(C)
Manuel Villareal
(M)
Sally Wenzel
(S)
Heidi Zafra
(H)
Tomasz Ziedalski
(T)
Commentaires et corrections
Type : ErratumIn
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