TY - JOUR
T1 - 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)
T2 - a randomised, controlled, phase 3b trial
AU - ANDHI study investigators
AU - Harrison, Tim W.
AU - Chanez, Pascal
AU - Menzella, Francesco
AU - Canonica, Giorgio Walter
AU - Louis, Renaud
AU - Cosio, Borja G.
AU - Lugogo, Njira L.
AU - Mohan, Arjun
AU - Burden, Annie
AU - McDermott, Lawrence
AU - Garcia Gil, Esther
AU - Zangrilli, James G.
AU - Pohl, Wolfgang
AU - Voves, Robert
AU - Deschampheleire, Maud
AU - Martinot, Jean Benoit
AU - Peché, Rudi
AU - Chapman, Kenneth
AU - Cheema, Amarjit
AU - Dorscheid, Delbert
AU - FitzGerald, J. Mark
AU - Gagnon, Remi
AU - Killorn, William Patrick
AU - Olivenstein, Ronald
AU - Philteos, George
AU - Ramsey, Clare
AU - Rolf, J. Douglass
AU - Walker, Brandie
AU - Hilberg, Ole
AU - Skjold, Tina
AU - Titlestad, Ingrid
AU - Hakulinen, Auli
AU - Kilpeläinen, Maritta
AU - Ben Hayoun, Michèle
AU - Bonniaud, Philippe
AU - Bourdin, Arnaud
AU - De Blay, Frédéric
AU - Deslee, Gaëtan
AU - Devouassoux, Gilles
AU - Didier, Alain
AU - Douadi, Youcef
AU - Fry, Stéphanie
AU - Garcia, Gilles
AU - Girodet, Pierre Olivier
AU - Leroyer, Christophe
AU - Magnan, Antoine
AU - Mahay, Guillaume
AU - Nocent, Cécilia
AU - Pison, Christophe
AU - Calhoun, William
N1 - Funding Information:
TWH reports grants from the National Institute for Health Research UK and AstraZeneca; and personal fees and non-financial support from AstraZeneca, GlaxoSmithKline (GSK), Vectura, Boehringer Ingelheim, Chiesi, and Synairgen. PC has served as an advisory board member, consultant, or lecturer, and has previously received honoraria or grants from ALK, Boehringer Ingelheim, Almirall, Centocor, GSK, Merck Sharp & Dohme, AstraZeneca, Novartis, Teva, Chiesi, Schering Plough, and Amu. FM has received research grants from AstraZeneca, Novartis, and Sanofi; and lecture fees and advisory board fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Mundipharma, Novartis, and Sanofi. GWC has previously received grant or research support from Boehringer Ingelheim, ALK, and Stallergenes; and honoraria or consultation fees from Menarini, GSK, Sanofi, Teva, Hal, AstraZeneca, and Novartis. RL has received unrestricted research grants from GSK, AstraZeneca, Novartis, and Chiesi; and lecture or advisory board fees from GSK, AstraZeneca, Novartis, and Sanofi. BGC has received honoraria for speaking at sponsored meetings from AstraZeneca, Teva, Mundipharma, Boehringer Ingelheim, Chiesi, Esteve, GSK, Novartis, and Rovi; he has received financial support to travel to meetings organised by Chiesi, Menarini, and Novartis; he acts as a consultant for ALK, AstraZeneca, Mundipharma, Chiesi, and Sanofi; and he has received funding or grant support for research projects from a variety of governmental agencies and not-for-profit foundations, as well as from Boehringer Ingelheim, AstraZeneca, Chiesi, Menarini, and Novartis. NLL received consulting fees from AstraZeneca and Teva; participated in advisory boards for AstraZeneca, Genentech, GSK, Novartis, Teva, and Sanofi; and received grants for clinical trials from AstraZeneca, Genentech, GSK, and Sanofi. AM declares no competing interests. TWH, PC, FM, GWC, RL, BGC, NLL, and AM were all ANDHI investigators and received institutional financial support to do the study. AB is a contract employee of AstraZeneca. LM was a contract employee of AstraZeneca during the time of the study. EGG is an employee of AstraZeneca and holds stock options. JGZ was an employee of AstraZeneca and held stock options during the time of the study.
Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021/3
Y1 - 2021/3
N2 - 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. Funding: AstraZeneca.
AB - 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. Funding: AstraZeneca.
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U2 - 10.1016/S2213-2600(20)30414-8
DO - 10.1016/S2213-2600(20)30414-8
M3 - Article
C2 - 33357499
AN - SCOPUS:85099581025
VL - 9
SP - 260
EP - 274
JO - The Lancet Respiratory Medicine
JF - The Lancet Respiratory Medicine
SN - 2213-2600
IS - 3
ER -