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 - Université de Reims Champagne-Ardenne Access content directly
Journal Articles The Lancet Respiratory Medicine Year : 2021

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 Harrison , Pascal Chanez , Francesco Menzella , Giorgio Walter Canonica , Renaud Louis , Borja Cosio , Njira Lugogo , Arjun Mohan , Annie Burden , Lawrence Mcdermott , Esther Garcia Gil , James Zangrilli , Wolfgang Pohl , Robert Voves , Maud Deschampheleire , Jean-Benoit Martinot , Rudi Peché , Kenneth Chapman , Amarjit Cheema , Delbert Dorscheid , J. Mark Fitzgerald , Remi 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 , Frédéric de Blay , Gaëtan Deslee , 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 Beghé , Francesco Blasi , Giovanna Carpagnano , Cristiano Caruso , Angelo Guido Corsico , Elio Constantino , Nunzio Crimi , Piero Maestrelli , Manlio Milanese , Alberto Papi , Girolamo Pelaia , Laura Pini , Pierachille Santus , Eleonora Savi , Nicola Scichilone , Gianenrico Senna , Giuseppe Spadaro , Adriano Vaghi , Steven Gans , Jurgen 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-Cosío Piqueras , Ana Gómez-Bastero Fernández , Ruperto González Pérez , 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 Nordstrom , 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 Gonzalez , 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 , Michael Marcus , Diego Jose Maselli Caceres , Vinay Mehta , Curtis Mello , Mark Millard , Aaron Milstone , 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 , Stephen Ryan , Sudhir Sekhsaria , Barry Sigal , Vinay Sikand , Weily Soong , Selwyn Spangenthal , Roy St. John , Gary Steven , Vijay Subramaniam , Kaharu Sumino , Eric Sztejman , Ricardo Tan , Tonny Tanus , Charles Thompson , Carl Thornblade , Manuel Villareal , Sally Wenzel , Heidi Zafra , Tomasz Ziedalski
Tim Harrison
  • Function : Author
Pascal Chanez
  • Function : Author
Francesco Menzella
  • Function : Author
Giorgio Walter Canonica
Renaud Louis
  • Function : Author
Borja Cosio
  • Function : Author
Njira Lugogo
  • Function : Author
Arjun Mohan
  • Function : Author
Annie Burden
  • Function : Author
Lawrence Mcdermott
  • Function : Author
Esther Garcia Gil
  • Function : Author
James Zangrilli
  • Function : Author
Wolfgang Pohl
  • Function : Author
Robert Voves
  • Function : Author
Maud Deschampheleire
  • Function : Author
Jean-Benoit Martinot
  • Function : Author
Rudi Peché
  • Function : Author
Kenneth Chapman
  • Function : Author
Amarjit Cheema
  • Function : Author
Delbert Dorscheid
  • Function : Author
J. Mark Fitzgerald
  • Function : Author
Remi Gagnon
  • Function : Author
William Patrick Killorn
  • Function : Author
Ronald Olivenstein
  • Function : Author
George Philteos
  • Function : Author
Clare Ramsey
  • Function : Author
J. Douglass Rolf
  • Function : Author
Brandie Walker
  • Function : Author
Ole Hilberg
  • Function : Author
Tina Skjold
  • Function : Author
Ingrid Titlestad
  • Function : Author
Auli Hakulinen
  • Function : Author
Maritta Kilpeläinen
  • Function : Author
Michèle Ben Hayoun
  • Function : Author
Philippe Bonniaud
Arnaud Bourdin
Frédéric de Blay
  • Function : Author
Gaëtan Deslee
  • Function : Author
Gilles Devouassoux
  • Function : Author
Alain Didier
Youcef Douadi
  • Function : Author
Stéphanie Fry
  • Function : Author
Gilles Garcia
  • Function : Author
Pierre-Olivier Girodet
  • Function : Author
Christophe Leroyer
  • Function : Author
Antoine Magnan
  • Function : Author
Guillaume Mahay
  • Function : Author
Cécilia Nocent
  • Function : Author
Christophe Pison
Pauline-Marie Roux
  • Function : Author
Camille Taillé
  • Function : Author
Juliana-Angelica Tiotiu
  • Function : Author
Ekkehard Beck
  • Function : Author
Margret Jandl
  • Function : Author
Christian Kaehler
  • Function : Author
Frank Kässner
  • Function : Author
Frank Koesters
  • Function : Author
Juliane Kronsbein
  • Function : Author
Thomas Schaum
  • Function : Author
Christian Schulz
  • Function : Author
Dirk Skowasch
  • Function : Author
Christian Taube
  • Function : Author
Tobias Welte
  • Function : Author
Andrés de Roux
  • Function : Author
Bianca Beghé
  • Function : Author
Francesco Blasi
  • Function : Author
Giovanna Carpagnano
  • Function : Author
Cristiano Caruso
  • Function : Author
Angelo Guido Corsico
Elio Constantino
  • Function : Author
Nunzio Crimi
  • Function : Author
Piero Maestrelli
  • Function : Author
Manlio Milanese
  • Function : Author
Alberto Papi
Girolamo Pelaia
  • Function : Author
Laura Pini
  • Function : Author
Pierachille Santus
  • Function : Author
Eleonora Savi
  • Function : Author
Nicola Scichilone
Gianenrico Senna
Giuseppe Spadaro
  • Function : Author
Adriano Vaghi
  • Function : Author
Steven Gans
  • Function : Author
Jurgen Hölters
  • Function : Author
B. Langeveld
  • Function : Author
Willem Pieters
  • Function : Author
G.H.A. Staaks
  • Function : Author
Ilonka van Veen
  • Function : Author
J.W.K. van den Berg
  • Function : Author
Gunnar Einvik
  • Function : Author
Sverre Lehmann
  • Function : Author
Ismael Ali García
  • Function : Author
Carlos Almonacid
  • Function : Author
Irina Bobolea
  • Function : Author
Paloma Campo Mozo
  • Function : Author
Gustavo de Luiz
  • Function : Author
Christian Domingo Ribas
  • Function : Author
Juan Luis García Rivero
  • Function : Author
Borja García-Cosío Piqueras
  • Function : Author
Ana Gómez-Bastero Fernández
  • Function : Author
Ruperto González Pérez
  • Function : Author
Aythamy Henríquez Santa
  • Function : Author
Carlos Martínez Rivera
  • Function : Author
Xavier Muñoz Gall
  • Function : Author
Jacinto Ramos
  • Function : Author
Jose Gregorio Soto Campos
  • Function : Author
Carmen Vidal Pan
  • Function : Author
Nikolai Stenfors
  • Function : Author
Alf Tunsäter
  • Function : Author
Ines Vinge
  • Function : Author
Rekha Chaudhuri
  • Function : Author
Timothy Harrison
  • Function : Author
Adel Mansur
  • Function : Author
Shuaib Nasser
  • Function : Author
Monica Nordstrom
  • Function : Author
Paul Pfeffer
  • Function : Author
Dinesh Saralaya
  • Function : Author
Philip Short
  • Function : Author
Arun Adlakha
  • Function : Author
Oral Alpan
  • Function : Author
Francis Averill
  • Function : Author
Anil Badhwar
  • Function : Author
Jose Bardelas
  • Function : Author
Barbara Baxter
  • Function : Author
George Bensch
  • Function : Author
William Berger
  • Function : Author
Jonathan Bernstein
Tracy Bridges
  • Function : Author
Ryan Brimeyer
  • Function : Author
William Calhoun
  • Function : Author
Edward Campbell
  • Function : Author
William Brett Cherry
  • Function : Author
Geoffrey Chupp
  • Function : Author
Lee Clore
  • Function : Author
John Cohn
  • Function : Author
Jeremy Cole
  • Function : Author
John Condemi
  • Function : Author
James Cury
  • Function : Author
Benjamin Davis
Samuel Deleon
  • Function : Author
Luis Delacruz
  • Function : Author
Joseph Diaz
  • Function : Author
  • PersonId : 181126
  • IdHAL : joseph-diaz
David Erb
  • Function : Author
Emeka Eziri
  • Function : Author
Faisal Fakih
  • Function : Author
Douglas Fiedler
  • Function : Author
David Fost
  • Function : Author
Stephen Fritz
  • Function : Author
Erika Gonzalez
  • Function : Author
Brad Goodman
  • Function : Author
Peter Gottlieb
  • Function : Author
Gregory Gottschlich
  • Function : Author
Richard Gower
  • Function : Author
Rizan Hajal
  • Function : Author
James Harris
  • Function : Author
Hengameh Heidarian-Raissy
  • Function : Author
Albrecht Heyder
  • Function : Author
David Hill
  • Function : Author
Fernando Holguin
  • Function : Author
Iftikhar Hussain
  • Function : Author
Jonathan Illowite
  • Function : Author
Joshua Jacobs
  • Function : Author
Mikell Jarratt
  • Function : Author
Harold Kaiser
  • Function : Author
Neil Kao
  • Function : Author
Ravindra Kashyap
  • Function : Author
David Kaufman
  • Function : Author
Edward Kent
  • Function : Author
Kenneth Kim
  • Function : Author
Ryan Klein
  • Function : Author
Monica Kraft
  • Function : Author
Ritsu Kono
  • Function : Author
Shahrukh Kureishy
  • Function : Author
Jeffrey Leflein
  • Function : Author
Mila Leong
  • Function : Author
Huamin Li
  • Function : Author
Robert Lin
  • Function : Author
Michael Marcus
  • Function : Author
Diego Jose Maselli Caceres
  • Function : Author
Vinay Mehta
  • Function : Author
Curtis Mello
  • Function : Author
Mark Millard
  • Function : Author
Aaron Milstone
  • Function : Author
Wendy Moore
  • Function : Author
Mark Moss
  • Function : Author
Nayla Mumneh
  • Function : Author
Thomas O'Brien
David Ostransky
  • Function : Author
Michael Palumbo
  • Function : Author
Purvi Parikh
  • Function : Author
Sudhir Parikh
  • Function : Author
Amit Patel
  • Function : Author
Guido Perez
  • Function : Author
Warren Pleskow
  • Function : Author
Bruce Prenner
  • Function : Author
Dileep Puppala
  • Function : Author
John Ramey
  • Function : Author
Joan Reibman
  • Function : Author
Ramon Reyes
  • Function : Author
Emory Robinette
  • Function : Author
Ileana Rodicio
  • Function : Author
Stephen Ryan
  • Function : Author
Sudhir Sekhsaria
  • Function : Author
Barry Sigal
  • Function : Author
Vinay Sikand
  • Function : Author
Weily Soong
  • Function : Author
Selwyn Spangenthal
  • Function : Author
Roy St. John
  • Function : Author
Gary Steven
  • Function : Author
Vijay Subramaniam
  • Function : Author
Kaharu Sumino
  • Function : Author
Eric Sztejman
  • Function : Author
Ricardo Tan
  • Function : Author
Tonny Tanus
  • Function : Author
Charles Thompson
  • Function : Author
Carl Thornblade
  • Function : Author
Manuel Villareal
  • Function : Author
Sally Wenzel
  • Function : Author
Heidi Zafra
  • Function : Author
Tomasz Ziedalski
  • Function : Author

Abstract

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<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 FEV1, PEF, ACQ-6, CGI-C, PGI-C, PSIA, and SNOT-22 at week 24 versus placebo, with differences observed early (within weeks 1 to 4). Adverse events were reported for 271 (63%) of 427 patients on benralizumab versus 143 (62%) of 229 patients on placebo. The most commonly reported adverse events for the 427 patients receiving benralizumab (frequency >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
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Dates and versions

hal-03170335 , version 1 (13-06-2022)

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Tim Harrison, Pascal Chanez, Francesco Menzella, Giorgio Walter Canonica, Renaud Louis, et al.. 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. The Lancet Respiratory Medicine, 2021, 9 (3), pp.260-274. ⟨10.1016/S2213-2600(20)30414-8⟩. ⟨hal-03170335⟩

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