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Craig LaForce,1 Frank C Albers,2 Mark Cooper,3 Anna Danilewicz,4 Lynn Dunsire,3 Robert Rees,4 Christy Cappelletti5 1North Carolina Clinical Research, Chapel Hill, NC, USA; 2Avillion, Northbrook, IL, USA; 3BioPharmaceuticals Research and Development, AstraZeneca, Cambridge, UK; 4Avillion, London, UK; 5BioPharmaceuticals Research and Development, AstraZeneca, Durham, NC, USACorrespondence: Mark Cooper, BioPharmaceuticals Reseach and Development, AstraZeneca, Cambridge, UK, Email mark.cooper1@astrazeneca.comPurpose: Decentralized clinical trials, where trial-related activities occur at locations other than traditional clinical sites(eg participant homes, local healthcare facilities), have the potential to improve trial access for people for whom time and/or distance constraints may impede participation. Albuterol–budesonide 180/160 μg pressurized metered-dose inhaler (pMDI) is FDA approved for the as-needed treatment or prevention of bronchoconstriction and to reduce the risk of exacerbations in patients with asthma 18 years or older. BATURA (NCT05505734) is a fully decentralized study, investigating as-needed albuterol–budesonide in participants with mild asthma.Methods: BATURA is a fully decentralized, phase 3b, randomized, double-blind, event-driven exacerbation study conducted in the United States. Participants aged ≥ 12 years using as-needed short-acting β2-agonist (SABA), alone or with low-dose inhaled corticosteroid or leukotriene receptor antagonist maintenance, are randomized 1:1 to as-needed albuterol–budesonide 180/160 μg or albuterol 180 μg pMDI for up to 52 weeks (minimum 12 weeks). Participants continue their current maintenance therapy, if applicable. Participants must have used SABA for ≥ 2 days in the 2 weeks pre-enrollment and have an Asthma Impairment Risk Questionnaire score ≥ 2 at screening and randomization. All trial-related visits, including screening and consent, are conducted virtually, with study medication shipped directly to each participant’s residence. The primary objective is to evaluate the efficacy of as-needed albuterol–budesonide versus albuterol on severe asthma exacerbation risk, measured by time-to-first severe asthma exacerbation (primary endpoint). Secondary endpoints include annualized rate of severe asthma exacerbation and total systemic corticosteroid exposure. Study medication use is captured via a Hailie sensor attached to the study medication pMDI. The intended sample size is 2500 participants.Conclusion: BATURA evaluates as-needed albuterol–budesonide in participants with mild asthma. The decentralized study model enables the trial to move out of research sites into participant homes, reducing participant burden and improving access.Keywords: decentralized clinical trials, trial design, albuterol–budesonide, SABA–ICS

Charlene M Prazma,1 Marco Idzko,2,3 Jo Anne Douglass,4 Arnaud Bourdin,5,6 Stephen Mallett,7 Frank C Albers,8 Steven W Yancey1 1Respiratory Therapeutic Area, GSK, Research Triangle Park, NC, USA; 2Division of Pneumology, Medical University of Vienna, Vienna, Austria; 3Department of Pneumology, University Hospital Freiburg, Freiburg, Germany; 4The Royal Melbourne Hospital and University of Melbourne, Melbourne, VIC, Australia; 5Departement de Pneumologie et Addictologie, Hôpital Arnaud de Villeneuve, CHU Montpellier, Montpellier, France; 6PhyMedExp, University of Montpellier, Montpellier, France; 7Clinical Statistics, GSK, Uxbridge, Middlesex, UK; 8Respiratory Medical Franchise, GSK, Research Triangle Park, NC, USACorrespondence: Charlene M PrazmaRespiratory Therapeutic Area, GSK, 5 Moore Drive, PO Box 13398, Research Triangle Park, NC, 27709, USATel +1 919 483 9013Email charlene.m.prazma@gsk.comPurpose: Improved understanding of characteristics that may influence treatment response across phenotypes may help guide treatment decisions.Patients and Methods: This was a post hoc analysis of MENSA, a multicenter, randomized, double-blind, placebo-controlled trial (NCT01691521). Patients aged ≥ 12 years with severe eosinophilic asthma received mepolizumab (75 mg intravenously or 100 mg subcutaneously) or placebo, plus standard of care, every 4 weeks for 32 weeks. Outcomes assessed were the annualized rate of clinically significant exacerbations and change from baseline in Asthma Control Questionnaire (ACQ)-5 score. Subgroup analyses were performed by baseline blood eosinophil count (< 150, ≥ 150– 300, ≥ 300 cells/μL) within atopic subgroups (non-atopic [specific immunoglobulin E < 0.35 kU/L], atopic [≥ 0.35– 17.5 kU/L], strongly atopic [> 17.5 kU/L]), and by house dust mite (HDM) sensitivity.Results: Of 576 patients analyzed, 272 were non-atopic, 181 were atopic and 94 were strongly atopic; 29 had missing atopy data. In patients with blood eosinophil counts ≥ 300 cells/μL, mepolizumab versus placebo reduced clinically significant exacerbations by 74%, 43% and 25% in the non-atopic, atopic and strongly atopic subgroups. Similar reductions were observed in all atopic subgroups in other blood eosinophil count categories where there were sufficient patient numbers for analysis, except for non-atopic patients with baseline blood eosinophil counts of < 150 cells/μL. Improvements in ACQ-5 scores of – 0.75, – 0.73 and – 0.78 with mepolizumab versus placebo were observed in non-atopic, atopic and strongly atopic patients with blood eosinophil counts ≥ 300 cells/μL; consistent improvements in ACQ-5 were not observed in patients with blood eosinophil counts < 150 or ≥ 150– 300 cells/μL. Reductions in clinically significant exacerbations with mepolizumab versus placebo were also observed irrespective of sensitivity to HDMs.Conclusion: Mepolizumab was associated with a trend for reductions in clinically significant exacerbations and improved asthma control versus placebo in patients with severe eosinophilic asthma, irrespective of atopic status or HDM sensitivity.Keywords: allergens and epitopes, eosinophils, asthma, asthma treatments, biologics

Hana Müllerová,1 Wilhelmine H Meeraus,1 Dmitry V Galkin,2 Frank C Albers,2 Sarah H Landis1,31Respiratory Epidemiology, GSK, Uxbridge, UK; 2Respiratory Medical Franchise, GSK, Uxbridge, NC, USA; 3Patient Centered Outcomes and Value Evidence and Outcomes, GSK, Collegeville, PA, USABackground: There are currently limited real-world data on the clinical burden of illness in patients with COPD who continue to exacerbate despite receiving triple therapy. The aim of this study was to compare the burden of COPD in patients with and without a phenotype characterized by a high blood eosinophil count and high risk of exacerbations while receiving triple therapy.Methods: This retrospective cohort study (GSK ID: 207323/PRJ2647) used UK Clinical Practice Research Datalink records linked with Hospital Episode Statistics. Eligible patients had a COPD medical diagnosis code recorded between January 1, 2004 and December 31, 2014, and a blood eosinophil count recorded on/after that date. Patients were followed from index date (first qualifying blood eosinophil count) until December 31, 2015. The study phenotype was defined as ≥2 moderate/≥1 severe acute exacerbation of COPD (AECOPD) in the year prior to the index date, current use of multiple-inhaler triple therapy (MITT), and blood eosinophil count ≥150 cells/μL on the index date. Outcomes measured during follow-up included moderate/severe AECOPDs, severe AECOPDs, all-cause mortality, primary care (GP) clinical consultations, and non-AECOPD-related unscheduled hospitalizations.Results: Of 46,814 patients eligible for inclusion, 2512 (5.4%) met the definition of the study phenotype. Adjusted rate ratios (95% CI) of moderate/severe AECOPDs and all-cause mortality in patients with the study phenotype versus those without were 2.32 (2.22, 2.43) and 1.26 (1.16, 1.37), respectively. For GP visits and non-AECOPD-related unscheduled hospitalizations, adjusted rate ratios (95% CI), in patients with the study phenotype versus those without, were 1.09 (1.05, 1.12) and 1.31 (1.18, 1.46), respectively.Conclusion: Patients with COPD and raised blood eosinophil counts who continue to exacerbate despite MITT represent a distinct subgroup who experience substantial clinical burden and account for high healthcare expenditure. There is a need for more effective management and therapeutic options for these patients.Keywords: acute exacerbations, burden of illness, eosinophils, multiple-inhaler triple therapy