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 / Tim W, Harrison; Pascal, Chanez; Francesco, Menzella; Giorgio Walter, Canonica; Renaud, Louis; Borja G, Cosio; Njira L, Lugogo; Arjun, Mohan; Annie, Burden; Lawrence, Mcdermott; Esther, Garcia Gil; Zangrilli, ; G, James; Pohl, Wolfgang; Voves, Robert; Deschampheleire, Maud; Louis, Renaud; Martinot, Jean-Benoit; Peché, Rudi; Chapman, Kenneth; Cheema, Amarjit; Dorscheid, Delbert; Mark FitzGerald, J; Gagnon, Remi; Patrick Killorn, William; Olivenstein, Ronald; Philteos, George; Ramsey, Clare; Douglass Rolf, J; Walker, Brandie; Hilberg, Ole; Skjold, Tina; Titlestad, Ingrid; Hakulinen, Auli; Kilpeläinen, Maritta; Ben Hayoun, Michèle; Bonniaud, Philippe; Bourdin, Arnaud; Chanez, Pascal; De Blay, Frédéric; Deslee, Gaëtan; Devouassoux, Gilles; Didier, Alain; Douadi, Youcef; Fry, Stéphanie; Garcia, Gilles; Girodet, Pierre-Olivier; Leroyer, Christophe; Magnan, Antoine; Mahay, Guillaume; Nocent, Cécilia; Pison, Christophe; Roux, Pauline-Marie; Taillé, Camille; Tiotiu, Juliana-Angelica; Beck, Ekkehard; Jandl, Margret; Kaehler, Christian; Kässner, Frank; Koesters, Frank; Kronsbein, Juliane; Schaum, Thomas; Schulz, Christian; Skowasch, Dirk; Taube, Christian; Welte, Tobias; de Roux, Andrés; Beghé, Bianca; Blasi, Francesco; Walter Canonica, Giorgio; Carpagnano, Giovanna; Caruso, Cristiano; Guido Corsico, Angelo; Constantino, Elio; Crimi, Nunzio; Maestrelli, Piero; Menzella, Francesco; Milanese, Manlio; Papi, Alberto; Pelaia, Girolamo; Pini, Laura; Santus, Pierachille; Savi, Eleonora; Scichilone, Nicola; Senna, Gianenrico; Spadaro, Giuseppe; Vaghi, Adriano; Gans, Steven; Hölters, Jurgen; Langeveld, B; Pieters, Willem; A Staaks, G H; van Veen, Ilonka; K van den Berg, J W; Einvik, Gunnar; Lehmann, Sverre; Ali García, Ismael; Almonacid, Carlos; Bobolea, Irina; Campo Mozo, Paloma; de Luiz, Gustavo; Domingo Ribas, Christian; María Echave-Sustaeta María-Tomé, José; Luis García Rivero, Juan; García-Cosío Piqueras, Borja; Gómez-Bastero Fernández, Ana; González Pérez, Ruperto; Henríquez Santa, Aythamy; Martínez Rivera, Carlos; Muñoz Gall, Xavier; Ramos, Jacinto; Gregorio Soto Campos, Jose; Vidal Pan, Carmen; Stenfors, Nikolai; Tunsäter, Alf; Vinge, Ines; Chaudhuri, Rekha; Harrison, Timothy; Mansur, Adel; Nasser, Shuaib; Nordstrom, Monica; Pfeffer, Paul; Saralaya, Dinesh; Short, Philip; Adlakha, Arun; Alpan, Oral; Averill, Francis; Badhwar, Anil; Bardelas, Jose; Baxter, Barbara; Bensch, George; Berger, William; Bernstein, Jonathan; Bridges, Tracy; Brimeyer, Ryan; Calhoun, William; Campbell, Edward; Brett Cherry, William; Chupp, Geoffrey; Clore, Lee; Cohn, John; Cole, Jeremy; Condemi, John; Cury, James; Davis, Benjamin; Deleon, Samuel; Delacruz, Luis; Diaz, Joseph; Erb, David; Eziri, Emeka; Fakih, Faisal; Fiedler, Douglas; Fost, David; Fritz, Stephen; Gonzalez, Erika; Goodman, Brad; Gottlieb, Peter; Gottschlich, Gregory; Gower, Richard; Hajal, Rizan; Harris, James; Heidarian-Raissy, Hengameh; Heyder, Albrecht; Hill, DAVID STANLEY; Holguin, Fernando; Hussain, Iftikhar; Illowite, Jonathan; Jacobs, Joshua; Jarratt, Mikell; Kaiser, Harold; Kao, Neil; Kashyap, Ravindra; Kaufman, David; Kent, Edward; Kim, Kenneth; Klein, Ryan; Kraft, Monica; Kono, Ritsu; Kureishy, Shahrukh; Leflein, Jeffrey; Leong, Mila; Li, Huamin; Lin, Robert; Lugogo, Njira; Marcus, Michael; Jose Maselli Caceres, Diego; Mehta, Vinay; Mello, Curtis; Millard, Mark; Milstone, Aaron; Mohan, Arjun; Moore, Wendy; Moss, Mark; Mumneh, Nayla; O'Brien, Thomas; Ostransky, David; Palumbo, Michael; Parikh, Purvi; Parikh, Sudhir; Patel, Amit; Perez, Guido; Pleskow, Warren; Prenner, Bruce; Puppala, Dileep; Ramey, John; Reibman, Joan; Reyes, Ramon; Robinette, Emory; Rodicio, Ileana; Ryan, Stephen; Sekhsaria, Sudhir; Sigal, Barry; Sikand, Vinay; Soong, Weily; Spangenthal, Selwyn; St John, Roy; Gary, Steven; Subramaniam, Vijay; Sumino, Kaharu; Sztejman, Eric; A Tan, Ricardo; Tanus, Tonny; Thompson, Charles; Thornblade, Carl; Villareal, Manuel; Wenzel, Sally; Zafra, Heidi; Ziedalski, Tomasz. - In: THE LANCET RESPIRATORY MEDICINE. - ISSN 2213-2600. - 9:3(2021), 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
Giuseppe Spadaro;David Hill;Gary Steven;
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
