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
- Authors: Harrison T.W.; Chanez P.; Menzella F.; Canonica G.W.; Louis R.; Cosio B.G.; Lugogo N.L.; Mohan A.; Burden A.; McDermott L.; Garcia Gil E.; Zangrilli J.G.; Pohl W.; Voves R.; Deschampheleire M.; Martinot J.-B.; Peche R.; Chapman K.; Cheema A.; Dorscheid D.; FitzGerald J.M.; Gagnon R.; Killorn W.P.; Olivenstein R.; Philteos G.; Ramsey C.; Rolf J.D.; Walker B.; Hilberg O.; Skjold T.; Titlestad I.; Hakulinen A.; Kilpelainen M.; Ben Hayoun M.; Bonniaud P.; Bourdin A.; De Blay F.; Deslee G.; Devouassoux G.; Didier A.; Douadi Y.; Fry S.; Garcia G.; Girodet P.-O.; Leroyer C.; Magnan A.; Mahay G.; Nocent C.; Pison C.; Roux P.-M.; Taille C.; Tiotiu J.-A.; Beck E.; Jandl M.; Kaehler C.; Kassner F.; Koesters F.; Kronsbein J.; Schaum T.; Schulz C.; Skowasch D.; Taube C.; Welte T.; de Roux A.; Beghe B.; Blasi F.; Carpagnano G.; Caruso C.; Corsico A.G.; Constantino E.; Crimi N.; Maestrelli P.; Milanese M.; Papi A.; Pelaia G.; Pini L.; Santus P.; Savi E.; Scichilone N.; Senna G.; Spadaro G.; Vaghi A.; Gans S.; Holters J.; Langeveld B.; Pieters W.; Staaks G.H.A.; van Veen I.; van den Berg J.W.K.; Einvik G.; Lehmann S.; Ali Garcia I.; Almonacid C.; Bobolea I.; Campo Mozo P.; de Luiz G.; Domingo Ribas C.; Echave-Sustaeta Maria-Tome J.M.; Garcia Rivero J.L.; Garcia-Cosio Piqueras B.; Gomez-Bastero Fernandez A.; Gonzalez Perez R.; Henriquez Santa A.; Martinez Rivera C.; Munoz Gall X.; Ramos J.; Gregorio Soto Campos J.; Vidal Pan C.; Stenfors N.; Tunsater A.; Vinge I.; Chaudhuri R.; Harrison T.; Mansur A.; Nasser S.; Nordstrom M.; Pfeffer P.; Saralaya D.; Short P.; Adlakha A.; Alpan O.; Averill F.; Badhwar A.; Bardelas J.; Baxter B.; Bensch G.; Berger W.; Bernstein J.; Bridges T.; Brimeyer R.; Calhoun W.; Campbell E.; Cherry W.B.; Chupp G.; Clore L.; Cohn J.; Cole J.; Condemi J.; Cury J.; Davis B.; DeLeon S.; Delacruz L.; Diaz J.; Erb D.; Eziri E.; Fakih F.; Fiedler D.; Fost D.; Fritz S.; Gonzalez E.; Goodman B.; Gottlieb P.; Gottschlich G.; Gower R.; Hajal R.; Harris J.; Heidarian-Raissy H.; Heyder A.; Hill D.; Holguin F.; Hussain I.; Illowite J.; Jacobs J.; Jarratt M.; Kaiser H.; Kao N.; Kashyap R.; Kaufman D.; Kent E.; Kim K.; Klein R.; Kraft M.; Kono R.; Kureishy S.; Leflein J.; Leong M.; Li H.; Lin R.; Lugogo N.; Marcus M.; Maselli Caceres D.J.; Mehta V.; Mello C.; Millard M.; Milstone A.; Moore W.; Moss M.; Mumneh N.; O'Brien T.; Ostransky D.; Palumbo M.; Parikh P.; Parikh S.; Patel A.; Perez G.; Pleskow W.; Prenner B.; Puppala D.; Ramey J.; Reibman J.; Reyes R.; Robinette E.; Rodicio I.; Ryan S.; Sekhsaria S.; Sigal B.; Sikand V.; Soong W.; Spangenthal S.; St. John R.; Steven G.; Subramaniam V.; Sumino K.; Sztejman E.; Tan R.A.; Tanus T.; Thompson C.; Thornblade C.; Villareal M.; Wenzel S.; Zafra H.; Ziedalski T.
- Publication year: 2021
- Type: Articolo in rivista
- OA Link: http://hdl.handle.net/10447/492735
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. Funding: AstraZeneca.