Abstract :
[en] BACKGROUND: Clinically meaningful improvement in the Sino-Nasal Outcome Test-22 (SNOT-22) was observed in patients with severe, eosinophilic asthma, and nasal polyposis (NP) treated with benralizumab in the ANDHI trial. A post hoc assessment of the effects of benralizumab on SNOT-22 response and asthma efficacy measures in these patients was conducted for further characterization of the efficacy and safety of benralizumab for patients with severe asthma and NP.
METHODS: Adults with severe, eosinophilic asthma who had experienced ≥2 prior-year exacerbations despite high-dosage inhaled corticosteroid plus additional controller[s] were randomized to 24 weeks of benralizumab or placebo. Patients with physician-diagnosed chronic rhinosinusitis with NP of any severity ongoing at baseline who consented to participate were included in the current ANDHI NP substudy population. Effect on NP symptoms was assessed by the SNOT-22, with an improvement of at least 8.9 defined as clinically significant (responder). Effects on chronic asthma outcomes were assessed by means of annualized asthma exacerbation rate (AER), St. George's Respiratory Questionnaire (SGRQ) total score, forced expiratory volume in one second (FEV1 ), and Asthma Control Questionnaire-6 (ACQ-6). All p-values were nominal.
RESULTS: Of the ANDHI population (n = 656), 23% (n = 153) participated in the NP substudy (n = 96 benralizumab; n = 57 placebo). Patients were 50% female, with mean age of 53 years, had prior-year AER = 3.3; mean pre-bronchodilator FEV1 = 55% predicted; and median blood eosinophil count = 510 cells/µl. For patients with high baseline SNOT-22 scores (>30), benralizumab treatment improved symptoms of NP as measured by SNOT-22 from baseline to Week 24 compared with placebo (Week 24: -10.44 [p = .0176]). Percentage of responders to SNOT-22 was greater for benralizumab vs. placebo (71.3% vs. 45.5%; p = .0036), and effect was enhanced for patients with high baseline SNOT-22 scores (>30). A 69% reduction vs. placebo in annualized AER (0.77 vs. 2.47; p < .0001) and greater clinically meaningful improvements from baseline in SGRQ total score (-16.7), FEV1 (+0.32 L), and ACQ-6 (-0.88) were observed (p < .0001). Benralizumab was well-tolerated. Frequency of adverse events (AEs) was similar for benralizumab (76.0%) and placebo (73.7%) groups. Most common AEs (frequency ≥5%) reported at a greater frequency in benralizumab vs. placebo included headache, sinusitis, pyrexia, and influenza.
CONCLUSIONS: These substudy data from ANDHI demonstrated the efficacy profile of benralizumab for patients with severe, eosinophilic asthma and NP, with improvement in SNOT-22 and asthma outcomes.
Funding text :
The authors thank the investigators, healthcare providers, research staff, patients, and caregivers who participated in the ANDHI trial. We also thank Nanna Keeling (AstraZeneca, Gothenburg, Sweden) for clinical operations leadership in this study. Writing and editing assistance, including preparation of a draft manuscript under the direction and guidance of the authors, incorporating author feedback, and manuscript submission, was provided by Wynne Dillon, MS (Kay Square Scientific, Newtown Square, PA, USA) and Michael A. Nissen, ELS (AstraZeneca, Gaithersburg, MD, USA). The authors thank James Kreindler (AstraZeneca, Gaithersburg, MD, USA) and Arnaud Bourdin (University of Montpellier, Montpellier, France) for support of data acquisition, statistical analysis, and interpretation of the study results for the comprehensive response analysis. This support was funded by AstraZeneca.AstraZeneca. The authors thank the investigators, healthcare providers, research staff, patients, and caregivers who participated in the ANDHI trial. We also thank Nanna Keeling (AstraZeneca, Gothenburg, Sweden) for clinical operations leadership in this study. Writing and editing assistance, including preparation of a draft manuscript under the direction and guidance of the authors, incorporating author feedback, and manuscript submission, was provided by Wynne Dillon, MS (Kay Square Scientific, Newtown Square, PA, USA) and Michael A. Nissen, ELS (AstraZeneca, Gaithersburg, MD, USA). The authors thank James Kreindler (AstraZeneca, Gaithersburg, MD, USA) and Arnaud Bourdin (University of Montpellier, Montpellier, France) for support of data acquisition, statistical analysis, and interpretation of the study results for the comprehensive response analysis. This support was funded by AstraZeneca.Giorgio Walter Canonica has previously received grant/research support from Boehringer Ingelheim, ALK, and Stallergenes, and honoraria or consultation fees from Menarini, GSK, Sanofi, Teva, Hal, AstraZeneca, and Novartis. Tim W. Harrison reports grants from the National Institute for Health Research, UK, and AstraZeneca; and personal fees and non‐financial support from AstraZeneca, GSK, Vectura, Boehringer Ingelheim, Chiesi, and Synairgen. Pascal Chanez has served as an advisory board member, consultant, or lecturer, and has previously received honoraria or grants from ALK, Boehringer Ingelheim, Almirall, Centocor, GSK, MSD, AstraZeneca, Novartis, Teva, Chiesi, Schering Plough, and Amu. Francesco Menzella has received research grants from AstraZeneca, Novartis, and Sanofi; lecture fees and advisory board fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Mundipharma, Novartis, and Sanofi. Renaud Louis has received unrestricted research grants from GSK, AstraZeneca, Novartis, and Chiesi, and lecture or advisory board fees from GSK, AstraZeneca, Novartis, and Sanofi. Borja G. Cosio has received honoraria for speaking at sponsored meetings from AstraZeneca, Teva, Mundipharma, Boehringer Ingelheim, Chiesi, Esteve, GSK, Novartis, and Rovi; he has received financial support to travel to meetings organized by Chiesi, Menarini, and Novartis, and he acts as a consultant for ALK, AstraZeneca, Mundipharma, Chiesi, and Sanofi, and has also received funding/grant support for research projects from a variety of governmental agencies and not‐for‐profit foundations, as well as from Boehringer Ingelheim, AstraZeneca, Chiesi, Menarini, and Novartis. Njira L. Lugogo received consulting fees from AstraZeneca and Teva; participated in advisory boards for AstraZeneca, Genentech, GSK, Novartis, Teva, and Sanofi; and received grants for clinical trials from AstraZeneca, Genentech, GSK, and Sanofi. Arjun Mohan has no conflicts to declare. Giorgio Walter Canonica, Tim W. Harrison, Pascal Chanez, Francesco Menzella, Renaud Louis, Borja G. Cosio, Njira L. Lugogo, and Arjun Mohan were all ANDHI investigators and received institutional financial support to conduct the study. Annie Burden is a contract employee of AstraZeneca. Esther Garcia Gil was an employee of AstraZeneca at the time of the study.
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