<b>Introduction/Background:</b> Biologics (Bx) are known to decrease specific biomarker levels: anti-IL5 reduces blood eosinophils (BEC) and anti-IgE slightly reduces FeNO. Anti-IL5 and anti-IgE are thought to have limited effect on total IgE (IgE). <b>Aims and Objectives:</b> To assess the proportions of severe asthma patients whose biomarkers (BEC, FeNO, and serum IgE) decrease following anti-IL5 and anti-IgE initiation. <b>Methods:</b> Patients in the International Severe Asthma Registry (ISAR) with biomarker and Bx data were included. From pre-Bx baseline to the post-Bx time period, the median (IQR) change in biomarker level and the proportion of patients with &gt;25% decrease in biomarkers were determined. <b>Results:</b> At 2-3 years from Bx initiation, BEC decreased by &gt;25% in 80.7% of anti-IL5 and 41.6% of anti-IgE patients. FeNO decreased by &gt;25% in 41.6% of anti-IL5 and 47.8% of anti-IgE patients. IgE decreased by &gt;25% in 41.7% of anti-IL5 and 15.6% of anti-IgE patients (Figure). <b>Figure:</b> Median (IQR) biomarker changes and patient proportions with decreased biomarkers in response to Bx. <b>Conclusions:</b> Anti-IL5 was superior in decreasing BEC and both Bx classes decreased FeNO to a limited extent. The lower proportion of anti-IgE patients with IgE reduction could be attributed to serum total IgE (not free IgE) measurement. Apart from anti-IL5's effect on BEC, &lt;50% patients had decreased biomarkers; the clinical implications should be explored.