Observational Analysis of Biological Remission as a Treatment Target for Severe Asthma: UK Severe Asthma Registry.

Abstract

The aim of biologic therapies in severe asthma is inhibition of type 2 (T2) inflammatory pathways. We hypothesized that patients who achieve complete suppression of IL-5 and IL-4/IL-13 pathways with biologic therapy (FeNO <20 ppb and blood eosinophil count <0.15 × 10⁹, considered biological remission) would have better outcomes than patients with incomplete suppression of T2 biology. This was a retrospective analysis of patients with severe asthma in the United Kingdom Severe Asthma Registry who met strict national access criteria for biologics. Characteristics before the biologic and at annual review were compared across biologic remission (BR) and non-BR. Of 778 patients, 148 (19%) had BR and 630 (81%) non-BR. Biologic remission did not confer additional benefit in exacerbation reduction, oral steroid exposure, lung function improvement, symptom improvement, or T2 biomarker reduction. The BR cohort was less T2 high before commencing biologics. Long disease duration (adjusted odds ratio [adjOR] = 1.96; 95% CI, 1.17-3.28), macrolide therapy (adjOR = 2.08; 95% CI, 1.17-3.71), and smoking history (adjOR = 1.63; 95% CI, 1.11-2.39) were positive predictors of BR, whereas higher T2 biomarkers predicted non-BR. However, blood eosinophil count and FeNO both had a negative correlation with lung function. Patients who achieve BR do not have superior outcomes compared with those who do not achieve BR. Biologic remission denotes a cohort of patients with a lower burden of T2 disease and additional factors driving disease severity. However, suppression of T2 biology is important for lung function gain. Prospective evaluation of treatment strategies that completely suppress IL-5 and IL-4/IL-13 pathways in T2 composite-high patients is needed.