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Introduction: International registries provide opportunities to describe use of biologics for treating severe asthma in current clinical practice. Our aims were to describe real-life global patterns of biologic use (continuation, switches, and discontinuations) for severe asthma, elucidate reasons underlying these patterns, and examine associated patient-level factors. Methods: This was a historical cohort study including adults with severe asthma enrolled into the International Severe Asthma Registry (ISAR; http://isaregistries.org, 2015-2020) or the CHRONICLE Study (2018-2020) and treated with a biologic. Eleven countries were included (Bulgaria, Canada, Denmark, Greece, Italy, Japan, Kuwait, South Korea, Spain, UK, and USA). Biologic utilization patterns were defined: 1) continuing initial biologic; 2) stopping biologic treatment; or 3) switching to another biologic. Reasons for discontinuation/switching were recorded and comparisons drawn between groups. Results: A total of 3531 patients were included. Omalizumab was the most common initial biologic in 2015 (88.2%) and benralizumab in 2019 (29.6%). Most patients (79%; 2791/3531) continued their first biologic; 10.2% (356/3531) stopped; 10.8% (384/3531) switched. The most frequent first switch was from omalizumab to an anti-IL-5/5R (49.6%; 187/377). The most common subsequent switch was from one anti-IL-5/5R to another (44.4%; 20/45). Insufficient efficacy and/or adverse effects were the most frequent reasons for stopping/switching. Patients who stopped/switched were more likely to have a higher baseline blood eosinophil count and exacerbation rate, lower lung function, and greater health care resource utilization. Conclusion: The description of real-life patterns of continuing, stopping, or switching biologics enhances our understanding of global biologic use. Prospective studies involving structured switching criteria could ascertain optimal strategies to identify patients who may benefit from switching.

Andrew N Menzies-Gow,1 Claire McBrien,2 Bindhu Unni,3 Celeste M Porsbjerg,4 Mona Al-Ahmad,5 Christopher S Ambrose,6 Karin Dahl Assing,7 Anna von Bülow,4 John Busby,8 Borja G Cosio,9 J Mark FitzGerald,10 Esther Garcia Gil,11 Susanne Hansen,12 Liam G aHeaney,8 Mark Hew,13,14 David J Jackson,15,16 Maria Kallieri,17 Stelios Loukides,17 Njira L Lugogo,18 Andriana I Papaioannou,17 Désirée Larenas-Linnemann,19 Wendy C Moore,20 Luis A Perez-de-Llano,21 Linda M Rasmussen,22 Johannes M Schmid,23 Salman Siddiqui,24 Marianna Alacqua,25 Trung N Tran,6 Charlotte Suppli Ulrik,26 John W Upham,27 Eileen Wang,28,29 Lakmini Bulathsinhala,3,30 Victoria A Carter,3,30 Isha Chaudhry,3,30 Neva Eleangovan,3,30 Ruth B Murray,3,30 Chris A Price,3,30 David B Price3,30,31 1UK Severe Asthma Network and National Registry, Royal Brompton & Harefield Hospitals, London, UK; 2Kingston Hospital, London, UK; 3Observational and Pragmatic Research Institute, Singapore, Singapore; 4Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark; 5Al-Rashed Allergy Center, Ministry of Health, Microbiology Department, Faculty of Medicine, Kuwait University, Kuwait, Kuwait; 6AstraZeneca, Gaithersburg, MD, USA; 7Department of Respiratory Medicine, Aalborg University Hospital, Aalborg, Denmark; 8UK Severe Asthma Network and National Registry, Queen’s University Belfast, Belfast, Northern Ireland; 9Son Espases University Hospital-IdISBa-Ciberes, Mallorca, Spain; 10The Centre for Lung Health, Vancouver Coastal Health Research Institute, UBC, Vancouver, Canada; 11AstraZeneca, Barcelona, Spain; 12Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark; 13Allergy, Asthma & Clinical Immunology Service, Alfred Health, Melbourne, Australia; 14Public Health and Preventive Medicine, Monash University, Melbourne, Australia; 15UK Severe Asthma Network andNational Registry, Guy’s and St Thomas’ NHS Trust, London, UK; 16School of Immunology &amp

Introduction: International registries provide opportunities to describe use of biologics for treating severe asthma in current clinical practice. Our aims were to describe real-life global patterns of biologic use (continuation, switches, and discontinuations) for severe asthma, elucidate reasons underlying these patterns, and examine associated patient-level factors. Methods: This was a historical cohort study including adults with severe asthma enrolled into the International Severe Asthma Registry (ISAR; http://isaregistries.org, 2015–2020) or the CHRONICLE Study (2018–2020) and treated with a biologic. Eleven countries were included (Bulgaria, Canada, Denmark, Greece, Italy, Japan, Kuwait, South Korea, Spain, UK, and USA). Biologic utilization patterns were defined: 1) continuing initial biologic; 2) stopping biologic treatment; or 3) switching to another biologic. Reasons for discontinuation/ switching were recorded and comparisons drawn between groups. Results: A total of 3531 patients were included. Omalizumab was the most common initial biologic in 2015 (88.2%) and benralizumab in 2019 (29.6%). Most patients (79%; 2791/3531) continued their first biologic; 10.2% (356/3531) stopped; 10.8% (384/3531) switched. The most frequent first switch was from omalizumab to an anti–IL-5/5R (49.6%; 187/377). The most common subsequent switch was from one anti–IL-5/5R to another (44.4%; 20/45). Insufficient efficacy and/or adverse effects were the most frequent reasons for stopping/switching. Patients who stopped/switched were more likely to have a higher baseline blood eosinophil count and exacerbation rate, lower lung function, and greater health care resource utilization. Conclusion: The description of real-life patterns of continuing, stopping, or switching biologics enhances our understanding of global biologic use. Prospective studies involving structured switching criteria could ascertain optimal strategies to identify patients who may benefit from switching.