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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 Harrison Pascal Chanez 1 Francesco Menzella Giorgio Walter Canonica Renaud Louis Borja Cosio Njira Lugogo Arjun Mohan Annie Burden Lawrence Mcdermott Esther Garcia Gil James Zangrilli Wolfgang Pohl Robert Voves Maud Deschampheleire Jean-Benoit Martinot Rudi Peché Kenneth Chapman Amarjit Cheema Delbert Dorscheid J. Mark Fitzgerald Remi Gagnon William Patrick Killorn Ronald Olivenstein George Philteos Clare Ramsey J. Douglass Rolf Brandie Walker Ole Hilberg Tina Skjold Ingrid Titlestad Auli Hakulinen Maritta Kilpeläinen Michèle Ben Hayoun Philippe Bonniaud Arnaud Bourdin 2, 3 Frédéric de Blay Gaëtan Deslee 4 Gilles Devouassoux Alain Didier Youcef Douadi Stéphanie Fry Gilles Garcia Pierre-Olivier Girodet Christophe Leroyer Antoine Magnan Guillaume Mahay Cécilia Nocent Christophe Pison Pauline-Marie Roux Camille Taillé Juliana-Angelica Tiotiu Ekkehard Beck Margret Jandl Christian Kaehler Frank Kässner Frank Koesters Juliane Kronsbein Thomas Schaum Christian Schulz Dirk Skowasch Christian Taube Tobias Welte Andrés de Roux Bianca Beghé Francesco Blasi Giovanna Carpagnano Cristiano Caruso Angelo Guido Corsico Elio Constantino Nunzio Crimi Piero Maestrelli Manlio Milanese Alberto Papi Girolamo Pelaia Laura Pini Pierachille Santus Eleonora Savi Nicola Scichilone Gianenrico Senna Giuseppe Spadaro Adriano Vaghi Steven Gans Jurgen Hölters B. Langeveld Willem Pieters G.H.A. Staaks Ilonka van Veen J.W.K. van den Berg Gunnar Einvik Sverre Lehmann Ismael Ali García Carlos Almonacid Irina Bobolea Paloma Campo Mozo Gustavo de Luiz Christian Domingo Ribas José María Echave-Sustaeta María-Tomé Juan Luis García Rivero Borja García-Cosío Piqueras Ana Gómez-Bastero Fernández Ruperto González Pérez Aythamy Henríquez Santa Carlos Martínez Rivera Xavier Muñoz Gall Jacinto Ramos Jose Gregorio Soto Campos Carmen Vidal Pan Nikolai Stenfors Alf Tunsäter Ines Vinge Rekha Chaudhuri Timothy Harrison Adel Mansur Shuaib Nasser Monica Nordstrom Paul Pfeffer Dinesh Saralaya Philip Short Arun Adlakha Oral Alpan Francis Averill Anil Badhwar Jose Bardelas Barbara Baxter George Bensch William Berger Jonathan Bernstein Tracy Bridges Ryan Brimeyer William Calhoun Edward Campbell William Brett Cherry Geoffrey Chupp Lee Clore John Cohn Jeremy Cole John Condemi James Cury Benjamin Davis Samuel Deleon Luis Delacruz Joseph Diaz David Erb Emeka Eziri Faisal Fakih Douglas Fiedler David Fost Stephen Fritz Erika Gonzalez Brad Goodman Peter Gottlieb Gregory Gottschlich Richard Gower Rizan Hajal James Harris Hengameh Heidarian-Raissy Albrecht Heyder David Hill Fernando Holguin Iftikhar Hussain Jonathan Illowite Joshua Jacobs Mikell Jarratt Harold Kaiser Neil Kao Ravindra Kashyap David Kaufman Edward Kent Kenneth Kim Ryan Klein Monica Kraft Ritsu Kono Shahrukh Kureishy Jeffrey Leflein Mila Leong Huamin Li Robert Lin Michael Marcus Diego Jose Maselli Caceres Vinay Mehta Curtis Mello Mark Millard Aaron Milstone Wendy Moore Mark Moss Nayla Mumneh Thomas O'Brien David Ostransky Michael Palumbo Purvi Parikh Sudhir Parikh Amit Patel Guido Perez Warren Pleskow Bruce Prenner Dileep Puppala John Ramey Joan Reibman Ramon Reyes Emory Robinette Ileana Rodicio Stephen Ryan Sudhir Sekhsaria Barry Sigal Vinay Sikand Weily Soong Selwyn Spangenthal Roy St. John Gary Steven Vijay Subramaniam Kaharu Sumino Eric Sztejman Ricardo Tan Tonny Tanus Charles Thompson Carl Thornblade Manuel Villareal Sally Wenzel Heidi Zafra Tomasz Ziedalski
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
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Submitted on : Tuesday, March 16, 2021 - 10:15:53 AM
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Tim Harrison, Pascal Chanez, Francesco Menzella, Giorgio Walter Canonica, Renaud Louis, et al.. 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. The Lancet Respiratory Medicine, Elsevier, 2021, 9 (3), pp.260-274. ⟨10.1016/S2213-2600(20)30414-8⟩. ⟨hal-03170335⟩



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