Observational analysis of biological remission as a treatment target for severe asthma: UK severe asthma registry
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Jane,McDowell P.;Charlene,Redmond;John,Busby;Pujan,Patel;David J,Jackson;Paul E,Pfeffer;Adel H,Mansur;Mitesh,Patel;Thomas,Brown;Hassan,Burhan;Rekha,Chaudhuri;Hitasha,Rupani;Liam G,Heaney
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2025
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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.
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The journal of allergy and clinical immunology.In practice