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.

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 / T.W. Harrison, P. Chanez, F. Menzella, G.W. Canonica, R. Louis, B.G. Cosio, N.L. Lugogo, A. Mohan, A. Burden, L. McDermott, E. Garcia Gil, J.G. Zangrilli, W. Pohl, R. Voves, M. Deschampheleire, J.-. Martinot, R. Peche, K. Chapman, A. Cheema, D. Dorscheid, J.M. FitzGerald, R. Gagnon, W.P. Killorn, R. Olivenstein, G. Philteos, C. Ramsey, J.D. Rolf, B. Walker, O. Hilberg, T. Skjold, I. Titlestad, A. Hakulinen, M. Kilpelainen, M. Ben Hayoun, P. Bonniaud, A. Bourdin, F. De Blay, G. Deslee, G. Devouassoux, A. Didier, Y. Douadi, S. Fry, G. Garcia, P.-. Girodet, C. Leroyer, A. Magnan, G. Mahay, C. Nocent, C. Pison, P.-. Roux, C. Taille, J.-. Tiotiu, E. Beck, M. Jandl, C. Kaehler, F. Kassner, F. Koesters, J. Kronsbein, T. Schaum, C. Schulz, D. Skowasch, C. Taube, T. Welte, A. de Roux, B. Beghe, F. Blasi, G. Carpagnano, C. Caruso, A.G. Corsico, E. Constantino, N. Crimi, P. Maestrelli, M. Milanese, A. Papi, G. Pelaia, L. Pini, P. Santus, E. Savi, N. Scichilone, G. Senna, G. Spadaro, A. Vaghi, S. Gans, J. Holters, B. Langeveld, W. Pieters, G.H.A. Staaks, I. van Veen, J.W.K. van den Berg, G. Einvik, S. Lehmann, I. Ali Garcia, C. Almonacid, I. Bobolea, P. Campo Mozo, G. de Luiz, C. Domingo Ribas, J.M. Echave-Sustaeta Maria-Tome, J.L. Garcia Rivero, B. Garcia-Cosio Piqueras, A. Gomez-Bastero Fernandez, R. Gonzalez Perez, A. Henriquez Santa, C. Martinez Rivera, X. Munoz Gall, J. Ramos, J. Gregorio Soto Campos, C. Vidal Pan, N. Stenfors, A. Tunsater, I. Vinge, R. Chaudhuri, T. Harrison, A. Mansur, S. Nasser, M. Nordstrom, P. Pfeffer, D. Saralaya, P. Short, A. Adlakha, O. Alpan, F. Averill, A. Badhwar, J. Bardelas, B. Baxter, G. Bensch, W. Berger, J. Bernstein, T. Bridges, R. Brimeyer, W. Calhoun, E. Campbell, W.B. Cherry, G. Chupp, L. Clore, J. Cohn, J. Cole, J. Condemi, J. Cury, B. Davis, S. DeLeon, L. Delacruz, J. Diaz, D. Erb, E. Eziri, F. Fakih, D. Fiedler, D. Fost, S. Fritz, E. Gonzalez, B. Goodman, P. Gottlieb, G. Gottschlich, R. Gower, R. Hajal, J. Harris, H. Heidarian-Raissy, A. Heyder, D. Hill, F. Holguin, I. Hussain, J. Illowite, J. Jacobs, M. Jarratt, H. Kaiser, N. Kao, R. Kashyap, D. Kaufman, E. Kent, K. Kim, R. Klein, M. Kraft, R. Kono, S. Kureishy, J. Leflein, M. Leong, H. Li, R. Lin, N. Lugogo, M. Marcus, D.J. Maselli Caceres, V. Mehta, C. Mello, M. Millard, A. Milstone, W. Moore, M. Moss, N. Mumneh, T. O'Brien, D. Ostransky, M. Palumbo, P. Parikh, S. Parikh, A. Patel, G. Perez, W. Pleskow, B. Prenner, D. Puppala, J. Ramey, J. Reibman, R. Reyes, E. Robinette, I. Rodicio, S. Ryan, S. Sekhsaria, B. Sigal, V. Sikand, W. Soong, S. Spangenthal, t.J.R. S, G. Steven, V. Subramaniam, K. Sumino, E. Sztejman, R.A. Tan, T. Tanus, C. Thompson, C. Thornblade, M. Villareal, S. Wenzel, H. Zafra, T. Ziedalski. - In: THE LANCET RESPIRATORY MEDICINE. - ISSN 2213-2600. - 9:3(2021 Mar), pp. 260-274. [10.1016/S2213-2600(20)30414-8]

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

F. Blasi
Membro del Collaboration Group
;
P. Santus
Membro del Collaboration Group
;
2021

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.
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