<b>Background:</b> Understanding of treatment response to biologic therapy for severe asthma in the real world remains limited. <b>Objective:</b> To examine multiple levels of response to biologic therapy in adults with severe asthma in ISAR. <b>Methods:</b> This multi-country (n=23), registry-based study included patients ≥18 years who initiated biologics (anti-IL5/5R, anti-IgE, anti-IL4/IL13). Response in the 12 months (min. 6 months) post-initiation among impaired patients (as defined in Figure 1) was assessed as: ≥50% reduction in exacerbation rate, ≥50% reduction in LTOCS daily dose, ≥1 level improvement in asthma control, and ≥100 mL increase in FEV1, alone or in combination of 2,3, 4 endpoints. <b>Results:</b> Of total 1986 eligible adults, median age was 54 years, 59.7% were female; 79.7%, 53.6%, 47.4%, and 53.1% of patients achieved response in exacerbation, LTOCS, asthma control, and FEV1, respectively. Treatment response ranged from 43.6% to 10.5% when extending the definition from 2 to 4 endpoints. Greater response was observed in patients treated with anti-IL5/5R and anti-IL4/IL13 (Figure 1). <b>Conclusion:</b> Biologic effectiveness is evidenced as a large proportion of patients achieved response in at least one endpoint. There is still unmet need as the majority were non-responders in composite 4 endpoints. Response varies by definition, thus, multiple endpoints should be considered to fully assess response to biologics.