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
- Function : Author
- PersonId : 767923
- ORCID : 0000-0001-8467-2557
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
- Function : Author
- PersonId : 767645
- ORCID : 0000-0002-3670-5622
Arnaud Bourdin
- Function : Author
- PersonId : 975030
- IdHAL : arnaud-bourdin
- ORCID : 0000-0002-4645-5209
- IdRef : 070160228
Frédéric de Blay
- Function : Author
Gaëtan Deslee
- Function : Author
Gilles Devouassoux
- Function : Author
Alain Didier
- Function : Author
- PersonId : 933609
- ORCID : 0000-0001-6230-9706
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
- Function : Author
- PersonId : 766182
- ORCID : 0000-0002-2152-6461
- IdRef : 066846692
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
- Function : Author
- PersonId : 798034
- ORCID : 0000-0002-8716-4694
Elio Constantino
- Function : Author
Nunzio Crimi
- Function : Author
Piero Maestrelli
- Function : Author
Manlio Milanese
- Function : Author
Alberto Papi
- Function : Author
- PersonId : 800445
- ORCID : 0000-0002-6924-4500
Girolamo Pelaia
- Function : Author
Laura Pini
- Function : Author
Pierachille Santus
- Function : Author
Eleonora Savi
- Function : Author
Nicola Scichilone
- Function : Author
- PersonId : 806297
- ORCID : 0000-0001-6400-6573
Gianenrico Senna
- Function : Author
- PersonId : 806298
- ORCID : 0000-0003-4172-3216
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
José María Echave-Sustaeta María-Tomé
- 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
- Function : Author
- PersonId : 780249
- ORCID : 0000-0002-3476-1196
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
- Function : Author
- PersonId : 804854
- ORCID : 0000-0002-4306-5950
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
- Function : Author
- PersonId : 769120
- ORCID : 0000-0002-8406-6626
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
Domains
Life Sciences [q-bio]
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2021 Harrison et al., Onset of effect and impact.pdf (58.14 Mo)
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