Observational analysis of biological remission as a treatment target for severe asthma: UK severe asthma registry
Jane, McDowell P Charlene, Redmond John, Busby Pujan, Patel David J, Jackson Paul E, Pfeffer Adel H, Mansur Mitesh, Patel Thomas, Brown Hassan, Burhan
Jane, McDowell P
Charlene, Redmond
John, Busby
Pujan, Patel
David J, Jackson
Paul E, Pfeffer
Adel H, Mansur
Mitesh, Patel
Thomas, Brown
Hassan, Burhan
Affiliation
Queen's University Belfast; Royal Brompton and Harefield NHS Foundation Trust; King's College London; Barts Health NHS Trust; University of Birmingham; University Hospitals Birmingham NHS Foundation Trust; University Plymouth NHS Trust; Portsmouth Hospitals NHS Trust; Liverpool University Hospitals NHS Foundation Trust; University of Liverpool; NHS Greater Glasgow and Clyde Health Board; University Hospital Southampton NHS Foundation Trust
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Publication date
2025-09-05
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Abstract
Background: The aim of biologic therapies in severe asthma is inhibition of T2 inflammatory pathways.
Objective: We hypothesized that patients who achieve complete suppression of IL-5 & IL4/IL13 pathways with biologic therapy (FeNO <20ppb & blood eosinophil count (BEC) <0.15x10ˆ9, 'biological remission') would have better outcomes than patients with incomplete suppression of T2 biology.
Methods: Retrospective analysis of severe asthma patients in the United Kingdom Severe Asthma Registry (UKSAR) who met strict national access criteria for biologics. Characteristics pre-biologic & at annual review were compared across biological remission (BR) & non-BR.
Results: Of 778 patients, 148 (19%) had BR and 630 (81%) non-BR. BR did not confer additional benefit in exacerbation reduction, oral steroid exposure, lung function improvement, symptom improvement or T2-biomarker reduction. The BR cohort were less T2-high prior to commencing biologics. Long disease duration (adjOR 1.96, 95% CI 1.17 to 3.28), macrolide therapy (adjOR 2.08, 95% CI 1.17 to 3.71), & smoking history (adjOR 1.63, 95% CI 1.11 to 2.39) were positive predictors of BR, while higher-T2 biomarkers predicted non-BR. However, BEC & FeNO both had a negative correlation with lung function.
Conclusion: Patients who achieve BR do not have superior outcomes compared to those who do not achieve BR. BR denotes a cohort of patients with a lower burden of T2 disease & additional factors driving disease severity. However, suppression of T2 biology is important for lung function gain. Prospective evaluation of treatment strategies that completely supress IL5 & IL4/13 pathways in T2-composite high patients is needed.
Citation
McDowell PJ, Redmond C, Busby J, Patel P, Jackson DJ, Pfeffer PE, Mansur AH, Patel M, Brown T, Burhan H, Chaudhuri R, Rupani H, Heaney LG. Observational Analysis of Biological Remission as a Treatment Target for Severe Asthma: UK Severe Asthma Registry. J Allergy Clin Immunol Pract. 2025 Dec;13(12):3264-3273.e10. doi: 10.1016/j.jaip.2025.08.027. Epub 2025 Sep 5.
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Article