Baseline Blood Eosinophils and Reduction of Asthma Exacerbations By Omalizumab in Children with Moderate-to-Severe Allergic Asthma

Rationale: Since eosinophils may predict response to omalizumab therapy, we evaluated blood eosinophil count as a predictive biomarker for response to omalizumab in children.  During the 24-week inhaled steroid dose-stable phase of a double-blind, randomized, controlled trial in children ≥6 to <12 years old with inadequately controlled, moderate-to-severe, allergic asthma, clinically significant asthma exacerbation rates were reduced by 31% (p=0.007) with omalizumab (75-375 mg every 2 or 4 weeks) versus placebo.

Methods: This posthoc exploratory Poisson regression analysis examined exacerbation rate reductions with omalizumab versus placebo at Week 24, stratified by baseline blood eosinophil subgroups: <300/μL (n=146), ≥300/μL (n=429), <400/μL (n=223), and ≥400/μL (n=352). Clinically significant exacerbations were defined as those requiring either systemic corticosteroid therapy or a doubling of baseline inhaled corticosteroid dose for ≥3 days.

Results: Baseline demographic and clinical characteristics were similar between treatment groups and within eosinophil strata. Mean (SD) age ranged from 8.2 (1.8) to 8.8 (1.8) years. Baseline mean (SD) percentage predicted prebronchodilator forced expiratory volume in 1 second (FEV₁) ranged from 83.6 (20.4) to 91.6 (13.2). Exacerbation rates were reduced by the following percentages (95% CI) with omalizumab versus placebo: <300/μL, 5% (-48%, 41%; p=0.83); ≥300/μL, 39% (15%, 56%; p=0.004); <400/μL, 15% (-30%, 44%; p=0.46); and ≥400/μL, 41% (15%, 59%; p=0.005).

Conclusions: Omalizumab significantly reduces exacerbations in children with moderate-to-severe allergic asthma. In children with elevated baseline eosinophil counts (≥300/μL), a significantly greater response to omalizumab was observed for asthma exacerbation reduction compared with placebo; children with lower baseline eosinophils had nonsignificant reductions in exacerbation rates.