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
Jane MP, Charlene R, John B, Pujan P, David J J, Paul E P, Adel H M, Mitesh P, Thomas B, Hassan B, Rekha C, Hitasha R, Liam G H. Observational analysis of biological remission as a treatment target for severe asthma: UK severe asthma registry. J Allergy Clin Immunol Pract. 2025 Sep 5:S2213-2198(25)00828-1. doi: 10.1016/j.jaip.2025.08.027. Epub ahead of print.
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Article