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

被引:122
作者
Harrison, Tim W. [1 ]
Chanez, Pascal [2 ]
Menzella, Francesco [3 ]
Canonica, Giorgio Walter [4 ,5 ]
Louis, Renaud [6 ,7 ]
Cosio, Borja G. [8 ,9 ]
Lugogo, Njira L. [10 ]
Mohan, Arjun [11 ]
Burden, Annie [12 ]
McDermott, Lawrence [13 ]
Garcia Gil, Esther [14 ]
Zangrilli, James G. [13 ]
机构
[1] Univ Nottingham, Nottingham Natl Inst Hlth Res Biomed Res Ctr, Resp Res Unit, Nottingham City Hosp, Nottingham NG5 1PB, England
[2] Aix Marseille Univ, Dept Resp Dis CIC Nord INSERM, INRAE, C2VN, Marseille, France
[3] Azienda USL Reggio Emilia IRCCS, Pneumol Unit, Santa Maria Nuova Hosp, Reggio Emilia, Italy
[4] Humanitas Univ, Milan, Italy
[5] IRCCS, Res Hosp, Milan, Italy
[6] Univ Liege, Liege, Belgium
[7] Ctr Hosp Univ Liege, Liege, Belgium
[8] Hosp Son Espases IdISBa, Palma De Mallorca, Spain
[9] Ciberes, Palma De Mallorca, Spain
[10] Univ Michigan, Med Ctr, Ann Arbor, MI USA
[11] East Carolina Univ, Brody Sch Med, Greenville, NC 27858 USA
[12] AstraZeneca, Cambridge, England
[13] AstraZeneca, Gaithersburg, MD USA
[14] AstraZeneca, Barcelona, Spain
关键词
D O I
10.1016/S2213-2600(20)30414-8
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
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 mu L, 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 1, 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 FEV 1, 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.
引用
收藏
页码:260 / 274
页数:15
相关论文
共 57 条
  • [1] American Academy of Allergy Asthma & Immunology, 2019, BIOLOGICS MANAGEMENT
  • [2] [Anonymous], 2019, Asthma
  • [3] Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials
    Bachert, Claus
    Han, Joseph K.
    Desrosiers, Martin
    Hellings, Peter W.
    Amin, Nikhil
    Lee, Stella E.
    Mullol, Joaquim
    Greos, Leon S.
    Bosso, John V.
    Laidlaw, Tanya M.
    Cervin, Anders U.
    Maspero, Jorge F.
    Hopkins, Claire
    Olze, Heidi
    Canonica, G. Walter
    Paggiaro, Pierluigi
    Cho, Seong H.
    Fokkens, Wytske J.
    Fujieda, Shigeharu
    Zhang, Mei
    Lu, Xin
    Fan, Chunpeng
    Draikiwicz, Steven
    Kamat, Siddhesh A.
    Khan, Asif
    Pirozzi, Gianluca
    Patel, Naimish
    Graham, Neil M. H.
    Ruddy, Marcella
    Staudinger, Heribert
    Weinreich, David
    Stahl, Neil
    Yancopoulos, George D.
    Mannent, Leda P.
    [J]. LANCET, 2019, 394 (10209) : 1638 - 1650
  • [4] Dupilumab improves health-related quality of life in patients with chronic rhinosinusitis with nasal polyposis
    Bachert, Claus
    Hellings, Peter W.
    Mullol, Joaquim
    Hamilos, Daniel L.
    Gevaert, Philippe
    Naclerio, Robert M.
    Joish, Vijay N.
    Chao, Jingdong
    Mannent, Leda P.
    Amin, Nikhil
    Abbe, Adeline
    Taniou, Christine
    Fan, Chunpeng
    Pirozzi, Gianluca
    Graham, Neil M. H.
    Mahajan, Puneet
    Staudinger, Heribert
    Khan, Asif
    [J]. ALLERGY, 2020, 75 (01) : 148 - 157
  • [5] Oral Glucocorticoid-Sparing Effect of Mepolizumab in Eosinophilic Asthma
    Bel, Elisabeth H.
    Wenzel, Sally E.
    Thompson, Philip J.
    Prazma, Charlene M.
    Keene, Oliver N.
    Yancey, Steven W.
    Ortega, Hector G.
    Pavord, Ian D.
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2014, 371 (13) : 1189 - 1197
  • [6] Comparative clinical and airway inflammatory features of asthma with or without nasal polyposis
    Bilodeau, Lara
    Boulay, Marie-Eve
    Prince, Philippe
    Boisvert, Pierre
    Boulet, Louis-Philippe
    [J]. RHINOLOGY, 2010, 48 (04) : 420 - 425
  • [7] Biospace, XOLAIR OMALIZUMAB SI
  • [8] Baseline patient factors impact on the clinical efficacy of benralizumab for severe asthma
    Bleecker, Eugene R.
    Wechsler, Michael E.
    FitzGerald, J. Mark
    Menzies-Gow, Andrew
    Wu, Yanping
    Hirsch, Ian
    Goldman, Mitchell
    Newbold, Paul
    Zangrilli, James G.
    [J]. EUROPEAN RESPIRATORY JOURNAL, 2018, 52 (04)
  • [9] Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial
    Bleecker, Eugene R.
    FitzGerald, J. Mark
    Chanez, Pascal
    Papi, Alberto
    Weinstein, Steven F.
    Barker, Peter
    Sproule, Stephanie
    Gilmartin, Geoffrey
    Aurivillius, Magnus
    Werkstrom, Viktoria
    Goldman, Mitchell
    [J]. LANCET, 2016, 388 (10056) : 2115 - 2127
  • [10] A Critical Look at the Efficacy and Costs of Biologic Therapy for Chronic Rhinosinusitis with Nasal Polyposis
    Brown, W. Colby
    Senior, Brent
    [J]. CURRENT ALLERGY AND ASTHMA REPORTS, 2020, 20 (06)