B32-31 Dupilumab Doubles the Likelihood of Achieving Clinical Asthma Remission in Patients With Moderate-To-Severe Type 2 Asthma: Win Ratio Analysis of Quest

Abstract Rationale Many patients with moderate-to-severe asthma achieve on-treatment clinical remission with dupilumab. Although there is currently no consensus definition for clinical asthma remission, most definitions include a sustained absence of asthma exacerbations, no use of oral corticosteroids, improvement or stabilization of lung function, and achievement of asthma control after ≥1 year. Clinical remission may be difficult to evaluate because individual components of the definition have varying clinical weight. For example, a patient with no asthma exacerbations after 1 year of treatment likely has less disease activity than a patient who achieves only asthma control. Widely used in cardiovascular and critical care medicine, win ratio analysis may provide greater power and flexibility to detect and quantify treatment effects, and allows multiple components of an endpoint to be evaluated hierarchically. We therefore aimed to compare, using win ratio analysis, the efficacy of dupilumab vs placebo in achieving clinical asthma remission in patients with moderate-to-severe asthma and type 2 inflammation. Methods During phase 3 randomized, double-blind, placebo-controlled QUEST (NCT02414854), patients ≥12 years of age with moderate-to-severe asthma received add-on dupilumab 200 mg/300 mg every 2 weeks or matched placebo for 52 weeks. Win ratio analysis was performed in patients with type 2 inflammation (baseline blood eosinophils ≥150 cells/µL or fractional exhaled nitric oxide ≥25 parts per billion). Patient pairs, each receiving dupilumab or placebo, were compared for components of the composite clinical asthma remission endpoint to evaluate dupilumab wins, ties, and placebo wins. The components comprised absence and fewer asthma exacerbations (defined as asthma deterioration requiring use of systemic corticosteroids for ≥3 days, or hospitalization or emergency room visit because of asthma, requiring systemic corticosteroids), lack of lung function deterioration, and achievement of asthma control. Results Patients receiving dupilumab (n = 992) were nearly twice as likely as patients receiving placebo (n = 527) to achieve the composite hierarchical endpoint of clinical asthma remission (win ratio 1.98 95% CI 1.68, 2.34; P0.0001) (i.e. for unpaired comparisons of any dupilumab recipient vs any placebo recipient, the chance of a composite dupilumab win was 66.5%, and the chance of a placebo win was 33.5%). Dupilumab was associated with a higher percentage of wins than placebo for all 4 components of the composite clinical remission endpoint (Table). Conclusion In adults and adolescents with moderate-to-severe type 2 asthma, dupilumab nearly doubled the odds of having improved outcomes in the composite hierarchical endpoint of clinical asthma remission during the 52-week treatment period. This abstract is funded by: Research sponsored by Sanofi and Regeneron Pharmaceuticals, Inc.