S135 Dupilumab efficacy vs standard of care in patients with uncontrolled, persistent asthma – a meta analysis

Introduction and Objectives Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4/IL-13, key drivers of type 2 inflammation in multiple diseases. We conducted a direct meta-analysis of effect of dupilumab vs standard of care (SOC) on annualized severe exacerbation rates (AER) and lung function in subgroups of asthma patients with an eosinophilic phenotype. Methods 3 eosinophilic patient subgroups were identified from the phase (P) 3 QUEST (NCT02414854; N=1,902) and P2b (NCT01854047; N=465) studies with baseline characteristics that matched the key inclusion criteria of clinical trials of anti-IL-5 biologics: (1) benralizumab (medium-/high-dose ICS/LABA, eosinophils ≥300 cells/µL, ≥2 previous exacerbations, age ≥12 years); (2) mepolizumab (high-dose ICS/LABA, eosinophils ≥150 cells/µL, ≥2 previous exacerbations, age ≥12 years); and (3) reslizumab (medium-/high-dose ICS/LABA, eosinophils ≥400 cells/µL, ≥1 previous exacerbation, age ≥18 years). Using frequentist meta-analysis, the estimates of effect of dupilumab vs SOC on AER (rate ratio [RR]) and mean difference in change in FEV1 from baseline at Week 24 were pooled from the P3/P2b studies for each subgroup. Number needed to treat (NNT, the inverse of the absolute rate reduction) for 1 fewer severe exacerbation per year for dupilumab vs SOC was estimated. Results Subgroup 1 had 439 (23.1%)/100 (21.5%); subgroup 2, 406 (21.3%)/112 (24.0%); and subgroup 3, 556 (29.2%)/128 (27.5%) patients from the P3/P2b studies, respectively. Dupilumab 200/300 mg every 2 weeks significantly reduced the AER in all 3 subgroups vs SOC. The exacerbation RR (95% CI) for subgroups 1, 2, 3, respectively, were 0.26 (0.21–0.33), 0.36 (0.29–0.44), and 0.29 (0.23–0.36), representing 64–74% relative exacerbation rate reduction. The NNT (95% CI) for severe exacerbations was 0.91 (0.853–1.005), 1.033 (0.931–1.18), and 1.107 (1.034–1.228), respectively. The SOC adjusted change from baseline at Week 24 in FEV1 (95% CI) in respective subgroups was 0.22L (0.14–0.31), 0.18L (0.04–0.31), and 0.25L (0.18−0.31). Conclusions Dupilumab significantly reduced severe exacerbation rates and improved lung function in subgroups of patients with uncontrolled, persistent, eosinophilic asthma. NNTs indicated that only 1 patient would need dupilumab treatment instead of SOC to have 1 fewer severe asthma exacerbation per year.