Tezepelumab attenuates exertional symptom burden in severe asthma: insights from a real-world cohort

Exertional symptom burden is an important yet insufficiently characterised component of morbidity in severe asthma. Tezepelumab, a monoclonal antibody targeting thymic stromal lymphopoietin (TSLP), reduces exacerbations and improves asthma control across phenotypes, but its effects on patient-reported exertional symptoms and physical activity limitation remain unclear.

We conducted a retrospective study in 24 adults with severe asthma initiating tezepelumab per GINA criteria. The 6-item Asthma Control Questionnaire (ACQ-6), Asthma Control Test (ACT), and mini-Asthma Quality of Life Questionnaire (miniAQLQ) were administered at baseline and at 3 (n = 24), 6 (n = 20), and 12 months (n = 16). Pre-specified exercise-related items were analysed alongside total scores using the Wilcoxon signed-rank test.

At baseline, patients had poorly controlled asthma (median ACQ-6 3.50/6, ACT 11/25, miniAQLQ 3.53/6) and moderate-to-severe airflow limitation (median FEV₁ 57% predicted). Total scores improved progressively over 12 months, with changes at months 6 and 12 exceeding the respective minimal clinically important differences. Exertion-related items showed consistent improvements at least as pronounced as total score changes. The largest improvements were in strenuous activity limitation (miniAQLQ Q12: median change +2.0, p = 0.006) and overall activity limitation (ACQ-6 Q3: median change -2.5, p = 0.008).

In severe asthma, Tezepelumab is associated with progressive attenuation of exertional symptoms over 12 months of real-world treatment. These associative findings are consistent with mechanistic data and support further prospective studies.