Real-World Effectiveness of Tezepelumab in Severe Asthma: A Comparative Analysis of High and Low T2 Phenotypes

<b>Background</b>: Tezepelumab has demonstrated efficacy in severe uncontrolled asthma (SUA), although real-world evidence remains limited. <b>Methods</b>: We included patients with SUA who completed at least 6 months of treatment. Lung function, eosinophil counts, IgE, FeNO, comorbidities, and changes in asthma control were assessed using ACT, ACQ, the VAS, and quality of life (AQLQ), as well as severe exacerbations (hospital admissions and emergency visits), oral corticosteroid (OCS) courses, OCS withdrawal/dose reduction, and reductions in maintenance and reliever medication. Response was evaluated using the FEOS and EXACTO scales. Baseline (T0) and 6-month (T6) outcomes were compared in the overall cohort and according to T2-high (eosinophilic/allergic) vs. T2-low phenotype. <b>Results</b>: A total of 33 patients were analyzed (58 ± 12 years; 94% women), with a high burden of comorbidities (88%), mainly rhinosinusitis (79%), obesity (41%), and smoking (37%). Of these, 45.5% had received prior biologic therapy. All patients were on high-dose ICS + LABA, frequently with LAMA and other controllers; 30% were on maintenance OCS. In the previous year, 49% had been hospitalized, 97% had attended the emergency department, and 100% required OCS courses. After 10 ± 3 months, the overall group showed significant improvement in VAS, ACT, ACQ, and AQLQ (<i>p</i> < 0.001), with a reduction in eosinophils, but no significant change in FEV1%. Severe exacerbations, emergency visits, hospitalizations, and OCS courses decreased markedly (<i>p</i> < 0.001). Among 10 patients on maintenance OCS, OCS were discontinued in 7 and reduced in 3; maintenance/reliever medication was also reduced. The T2-high phenotype showed a higher likelihood of "complete response" (52% vs. 17% in non-T2), although "good response" predominated in non-T2; this difference was significant (<i>p</i> = 0.04). <b>Conclusions</b>: Tezepelumab improved asthma control and reduced healthcare utilization and corticosteroid use in both T2 and non-T2 patients, achieving clinical remission in 40%, with better outcomes in T2.