The Lancet Respiratory Medicine, volume 9, issue 3, pages 260-274
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
Tim W Harrison
,
Borja G Cosío
,
Njira L. Lugogo
,
Annie Burden
,
Lawrence McDermott
,
Esther Garcia Gil
,
James G. Zangrilli
,
Wolfgang Pohl
,
Robert Voves
,
Maud Deschampheleire
,
Renaud Louis
,
Jean Benoit Martinot
,
Rudi Peché
,
Kenneth Chapman
,
Amarjit Cheema
,
Delbert Dorscheid
,
J. Mark FitzGerald
,
Rémi Gagnon
,
William Patrick Killorn
,
Ronald Olivenstein
,
George Philteos
,
Clare Ramsey
,
J. Douglass Rolf
,
Brandie Walker
,
Ole Hilberg
,
Tina Skjold
,
Ingrid Titlestad
,
Auli Hakulinen
,
Maritta Kilpeläinen
,
Michèle Ben Hayoun
,
Philippe Bonniaud
,
Arnaud Bourdin
,
Pascal Chanez
,
Frederic de Blay
,
Gaëtan Deslée
,
Gilles Devouassoux
,
Alain Didier
,
Youcef Douadi
,
Stéphanie Fry
,
Gilles Garcia
,
Pierre-Olivier Girodet
,
Christophe Leroyer
,
Antoine Magnan
,
Guillaume Mahay
,
Cécilia Nocent
,
Christophe Pison
,
Pauline Marie Roux
,
Camille Taillé
,
Juliana Angelica Tiotiu
,
Ekkehard Beck
,
Margret Jandl
,
Christian Kaehler
,
Frank Käßner
,
Frank Koesters
,
Juliane Kronsbein
,
Thomas Schaum
,
CHRISTIAN SCHULZ
,
Dirk Skowasch
,
Christian Taube
,
Tobias Welte
,
Andrés de Roux
,
Bianca Beghè
,
Francesco Blasi
,
Giorgio Walter Canonica
,
Giovanna Carpagnano
,
Cristiano Caruso
,
Angelo Guido Corsico
,
Elio Constantino
,
Nunzio Crimi
,
Piero Maestrelli
,
Francesco Menzella
,
Manlio Milanese
,
Alberto Papi
,
Girolamo Pelaia
,
Laura Pini
,
Pierachille Santus
,
Eleonora Savi
,
Nicola Scichilone
,
Gianenrico Senna
,
Giuseppe Spadaro
,
Adriano Vaghi
,
Steven Gans
,
Jürgen Hölters
,
B. Langeveld
,
Willem Pieters
,
G H A Staaks
,
Ilonka van Veen
,
J. W. K. van den Berg
,
Gunnar Einvik
,
Sverre Lehmann
,
Ismael Ali García
,
Carlos Almonacid
,
Irina Bobolea
,
Paloma Campo Mozo
,
Gustavo De Luiz
,
Christian Domingo Ribas
,
José María Echave Sustaeta María Tomé
,
Juan Luis García Rivero
,
Borja García Cosio Piqueras
,
Ana Gómez Bastero Fernández
,
Ruperto Gonzalez Perez
,
Aythamy Henríquez Santa
,
Carlos Martínez Rivera
,
Xavier Muñoz Gall
,
Jacinto Ramos
,
Jose Gregorio Soto Campos
,
Carmen Vidal Pan
,
Nikolai Stenfors
,
Alf Tunsäter
,
Ines Vinge
,
Rekha Chaudhuri
,
TIMOTHY HARRISON
,
Adel Mansur
,
Shuaib Nasser
,
Monica Nordström
,
Paul Pfeffer
,
Dinesh Saralaya
,
Philip Short
,
Arun Adlakha
,
Oral Alpan
,
Francis Averill
,
Anil Badhwar
,
Jose Bardelas
,
Barbara Baxter
,
GEORGE BENSCH
,
William Berger
,
Jonathan Bernstein
,
Tracy Bridges
,
Ryan Brimeyer
,
William Calhoun
,
Edward Campbell
,
William Brett Cherry
,
Geoffrey Chupp
,
Lee Clore
,
John Cohn
,
Jeremy Cole
,
John Condemi
,
James Cury
,
Benjamin Davis
,
Samuel DeLeon
,
Luis DeLaCruz
,
Joseph Diaz
,
David Erb
,
Emeka Eziri
,
Faisal Fakih
,
Douglas Fiedler
,
David Fost
,
Stephen Fritz
,
Erika González
,
Brad Goodman
,
Peter Gottlieb
,
Gregory Gottschlich
,
Richard Gower
,
Rizan Hajal
,
James Harris
,
Hengameh Heidarian Raissy
,
Albrecht Heyder
,
David Hill
,
Fernando Holguin
,
Iftikhar Hussain
,
Jonathan Illowite
,
Joshua Jacobs
,
Mikell Jarratt
,
Harold Kaiser
,
Neil Kao
,
Ravindra Kashyap
,
David Kaufman
,
Edward Kent
,
KENNETH KIM
,
Ryan Klein
,
Monica Kraft
,
Ritsu Kono
,
Shahrukh Kureishy
,
Jeffrey Leflein
,
Mila Leong
,
Huamin Li
,
Robert Lin
,
Njira Lugogo
,
Michael Marcus
,
Diego Jose Maselli Caceres
,
Vinay Mehta
,
Curtis Mello
,
Mark Millard
,
Aaron Milstone
,
Arjun Mohan
,
Wendy Moore
,
Mark Moss
,
Nayla Mumneh
,
Thomas O'Brien
,
David Ostransky
,
Michael Palumbo
,
Purvi Parikh
,
Sudhir Parikh
,
Amit Patel
,
Guido Perez
,
Warren Pleskow
,
Bruce Prenner
,
Dileep Puppala
,
John Ramey
,
Joan Reibman
,
Ramon Reyes
,
Emory Robinette
,
Ileana Rodicio
,
Ryan Stephen
,
Sudhir Sekhsaria
,
Barry Sigal
,
Vinay Sikand
,
Weily Soong
,
Selwyn Spangenthal
,
Roy St John
,
Steven Gary
,
Vijay Subramaniam
,
Kaharu Sumino
,
Eric Sztejman
,
Ricardo A. Tan
,
Tonny Tanus
,
Charles Thompson
,
Carl Thornblade
,
Manuel Villareal
,
Sally Wenzel
,
Heidi Zafra
,
Tomasz Ziedalski
Publication type: Journal Article
Publication date: 2021-03-01
Journal:
The Lancet Respiratory Medicine
scimago Q1
SJR: 7.965
CiteScore: 87.1
Impact factor: 38.7
ISSN: 22132600, 22132619
Pulmonary and Respiratory Medicine
Abstract
Summary 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), FEV1, peak expiratory flow (PEF), ACQ-6, Predominant Symptom and Impairment Assessment (PSIA), Clinician Global Impression of Change (CGI-C), Patient Global Impression of Change (PGI-C), and Sino-Nasal Outcome Test-22 (SNOT-22). All efficacy analyses, except for SNOT-22, were summarised and analysed using the full analysis set on an intention-to-treat population (all randomly assigned patients receiving investigational product, regardless of protocol adherence or continued participation in the study). SNOT-22 was summarised for the subgroup of patients with physician-diagnosed nasal polyposis with informed consent. This study is registered with ClinicalTrials.gov, NCT03170271. 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 5%) were nasopharyngitis (30 [7%]), headache (37 [9%]), sinusitis (28 [7%]), bronchitis (22 [5%]), and pyrexia (26 [6%]). Fewer serious adverse events were reported for benralizumab (23 [5%]) versus placebo (25 [11%]), and the only common serious adverse event (experienced by >1% of patients) was worsening of asthma, which was reported for nine (2%) patients in the benralizumab group and nine (4%) patients in the placebo group. 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.
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