Real-World Effectiveness of Tezepelumab Across T2 and Non-T2 Severe Asthma Phenotypes: A Multicenter Spanish Cohort...

To evaluate real-world effectiveness of tezepelumab in severe asthma, by type-2 (T2) status and prior biologic exposure, and response predictors.

Multicentre retrospective cohort in 17 Spanish tertiary hospitals. Adults with ERS/ATS-defined severe asthma initiating tezepelumab were identified from pharmacy dispensing records. Outcomes included Asthma Control Test (ACT), annualised exacerbations, oral corticosteroid (OCS) exposure (maintenance use, prednisone>5mg/day, cumulative dose), spirometry (FEV₁; % predicted), blood eosinophils and fractional exhaled nitric oxide (FeNO). Linear regression assessed predictors of change in ACT and exacerbations.

Of 307 initiators, 304 had paired assessments. Mean ACT rose from 13.6 to 17.0 (+3.4) and annualised exacerbations fell from 2.9 to 0.8; 47% were exacerbation-free. Maintenance OCS use decreased from 22.4% to 16.8%, and prednisone>5mg/day fell from 22.4% to 6.9% (70% reduction). Cumulative OCS dose declined from 1575 to 1020mg (median 420 to 0mg). Mean FEV₁ increased from 1850 to 1930mL and % predicted from 70.4% to 73.7%, with larger gains at baseline FEV₁<80% predicted. Clinical remission was achieved in 12.3% of patients. At follow-up, 54.8% had eosinophils<150cells/μL and 74.6% had FeNO<25ppb. Prior biologic exposure predicted smaller improvements in ACT and exacerbations.

In specialist care, tezepelumab was associated with meaningful improvements in asthma control, fewer exacerbations, reduced OCS exposure, modest lung function gains, and reductions in T2 biomarkers across phenotypes. Exploratory analyses identified age, sex, prior OCS use, T2 status and prior biologic exposure as response predictors. Future comparative studies are needed to confirm causality.