Dupilimab Efficacy in Patients with Uncontrolled, Moderate-to-Severe Asthma by Body Mass Index

<b>Introduction:</b> Obesity is associated with increased asthma severity, poor asthma control, and poor response to inhaled corticosteroids. Dupilumab (DPL), a fully human monoclonal antibody blocks the shared receptor component for interleukin (IL)-4/IL-13, key drivers of type 2 inflammation. In the phase 3 QUEST trial (NCT02414854), add-on DPL 200/300 mg every 2 wks (q2w) vs placebo (PBO) reduced severe exacerbations and improved pre-bronchodilator (BD) FEV₁ in patients (pts) with uncontrolled, moderate-to-severe asthma. <b>Aim:</b> To assess the effect of baseline (BL) body mass index (BMI) on DPL efficacy in uncontrolled, moderate-to-severe asthma pts. <b>Methods:</b> Annualized rate of severe exacerbations during the 52-wk treatment period and LS mean (LSM) change from BL at Wk 12 in pre-BD FEV₁ were assessed by BL BMI subgroups (&lt;25, 25–&lt;30, ≥30 kg/m²). <b>Results:</b> Across all BL BMI subgroups, both DPL 200 and 300 mg q2w vs PBO consistently reduced severe exacerbations (–35.1 to –51.4%; all P&lt;0.05) and improved FEV₁ at Wk 12 (LSM difference: 0.09–0.17; all P&lt;0.05 except in the 25–&lt;30 kg/m² subgroup treated with 200 mg [P=0.09]) (Figure). The most frequent AE in the DPL 200/300 mg groups vs PBO groups was injection-site reaction (15%/18% vs 5%/10%, respectively). <b>Conclusion:</b> Dupilumab reduced severe exacerbations and improved FEV₁ in pts with uncontrolled, moderate-to-severe asthma, regardless of BL BMI or DPL dose received.