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
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Harrison, Tim | Chanez, Pascal | Menzella, Francesco | Canonica, Giorgio Walter | Louis, Renaud | Cosio, Borja | Lugogo, Njira | Mohan, Arjun | Burden, Annie | Mcdermott, Lawrence | Garcia Gil, Esther | Zangrilli, James | Pohl, Wolfgang | Voves, Robert | Deschampheleire, Maud | Martinot, Jean-Benoit | Peché, Rudi | Chapman, Kenneth | Cheema, Amarjit | Dorscheid, Delbert | Fitzgerald, J. Mark | Gagnon, Remi | Killorn, William Patrick | Olivenstein, Ronald | Philteos, George | Ramsey, Clare | Rolf, J. Douglass | Walker, Brandie | Hilberg, Ole | Skjold, Tina | Titlestad, Ingrid | Hakulinen, Auli | Kilpeläinen, Maritta | Ben Hayoun, Michèle | Bonniaud, Philippe | Bourdin, Arnaud | 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 | Carpagnano, Giovanna | Caruso, Cristiano | Corsico, Angelo Guido | Constantino, Elio | Crimi, Nunzio | Maestrelli, Piero | 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 | Staaks, G.H.A. | van Veen, Ilonka | van den Berg, J.W.K. | Einvik, Gunnar | Lehmann, Sverre | Ali García, Ismael | Almonacid, Carlos | Bobolea, Irina | Campo Mozo, Paloma | de Luiz, Gustavo | Domingo Ribas, Christian | Echave-Sustaeta María-Tomé, José María | García Rivero, Juan Luis | 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 | Cherry, William Brett | 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 | 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 | Marcus, Michael | Maselli Caceres, Diego Jose | Mehta, Vinay | Mello, Curtis | Millard, Mark | Milstone, Aaron | 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 | Steven, Gary | Subramaniam, Vijay | Sumino, Kaharu | Sztejman, Eric | Tan, Ricardo | Tanus, Tonny | Thompson, Charles | Thornblade, Carl | Villareal, Manuel | Wenzel, Sally | Zafra, Heidi | Ziedalski, Tomasz
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International audience.
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
