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<b>Background</b>: Severe asthma remains associated with substantial morbidity despite optimized inhaled therapy. Biologic agents targeting type 2 inflammation improve clinical outcomes; however, real-world evidence regarding the durability of these effects beyond the first treatment year remains limited. The present study extends the follow-up of a previously reported real-world cohort in which 12-month outcomes of biologic therapy were evaluated. <b>Methods</b>: We conducted a retrospective observational longitudinal study of adults with severe asthma treated with omalizumab, benralizumab, or dupilumab at a tertiary center in Târgu-Mureș, Romania, between 2020 and 2025, extending follow-up of a previously published real-world cohort. The same patient cohort was followed for an additional period, with longitudinal data collected up to 24 months after biologic therapy initiation. Clinical, functional, and biomarker outcomes were assessed at baseline, 12 months, and 24 months, including Asthma Control Test (ACT) score, forced expiratory volume in one second (FEV<sub>1</sub>% predicted), annual exacerbation rate, blood eosinophil count, and fractional exhaled nitric oxide (FeNO). Remission was defined as clinical (ACT ≥ 20, no severe exacerbations, and no maintenance oral corticosteroids), biological (FeNO < 20 ppb and blood eosinophils < 150/µL), and complete (both clinical and biological). Longitudinal changes were analyzed using the Friedman test with post hoc Wilcoxon signed-rank tests. <b>Results</b>: Forty-eight patients were included at baseline, and 41 had available data at 24 months. ACT scores improved from 12 (IQR 11-14) at baseline to 23 (21-25) at 12 months and remained stable at 22 (20-25) at 24 months (<i>p</i> < 0.001). Predicted FEV<sub>1</sub>% increased from 50 (39-59) to 78 (68-88) at 12 months and 79 (66-96) at 24 months (<i>p</i> < 0.001). Blood eosinophil counts were markedly suppressed, and FeNO levels continued to decrease over time. Exacerbations declined from 2 (2-3) per year at baseline to 0 and 0.5 (0-1) at 12 and 24 months, respectively (<i>p</i> < 0.001). At 24 months, clinical, biological, and complete remission were observed in 61.0%, 78.0%, and 41.5% of patients with available paired data, respectively. <b>Conclusions</b>: Biologic therapy was associated with sustained clinical and functional improvement over 24 months, accompanied by sustained improvement in type 2 airway inflammation and increasing proportions of patients meeting remission criteria in real-world practice.