Multidomain clinical and biological remission with tezepelumab in severe asthma: a 12-month multicentre real-world study

Abstract

Background: Tezepelumab, an anti–TSLP monoclonal antibody, has shown broad efficacy across severe asthma phenotypes. However, real-world evidence evaluating multidomain remission—integrating clinical, functional, and inflammatory domains—remains limited. The primary objective was to assess 12-month effectiveness and multidomain remission (clinical, biological, and complete remission) stratified by inflammatory phenotype, in a prospective multicentre real-world cohort of patients with severe asthma treated with tezepelumab. Methods: This prospective observational study included adults with severe asthma initiating tezepelumab across 14 specialised severe asthma units in Spain. Clinical outcomes (exacerbations, ACT, OCS use), lung function, and type 2 (T2) biomarkers (blood eosinophils, FeNO) were evaluated at baseline and 12 months. Clinical remission was defined using strict (no exacerbations, no maintenance OCS, ACT ≥ 20, FEV₁ ≥80%) and pragmatic criteria (no exacerbations, no OCS, ACT ≥ 20, and no FEV₁ decline > 5%). Biological remission required FeNO < 25 ppb and eosinophils < 300/µL. Results: Ninety-three patients were included. The annualised exacerbation rate decreased by 68% (3.59 to 1.14; p < 0.001). ACT improved from 13.7 to 19.9 (p < 0.001) and 77.8% of patients achieved an ACT increase ≥ 3 points. Maintenance OCS use fell from 40% to 21% (p < 0.01). FEV₁ (% predicted) increased from 70.7% to 75.6% (p < 0.001). T2 biomarkers significantly decreased (eosinophils p = 0.004; FeNO p = 0.034). Of the 93 patients included, 86 had complete data for strict clinical remission analysis. Among evaluable patients, 22.1% (19/86) achieved strict clinical remission and 38.4% (33/86) pragmatic remission. Biological remission occurred in 73.1% (38/52), and complete remission in 22.0% (11/50). Conclusion: In this multicentre real-world cohort, tezepelumab produced sustained multidomain improvements with consistent benefit across phenotypes, including marked exacerbation reductions in allergic biologic-naïve patients. Incorporating biological remission into a multidomain framework provides new insight into the depth and heterogeneity of response achievable with upstream TSLP blockade.