B32-11 Efficacy of Dupilumab With Medium Inhaled Corticosteroid Dose Versus Omalizumab With High Inhaled Corticosteroid Dose in Patients With Coexisting Chronic Rhinosinusitis With Nasal Polyps and Uncontrolled Asthma: Post Hoc Analysis of Everest

Rationale Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) often have coexisting diseases, including asthma. Patients with asthma uncontrolled on medium-dose inhaled corticosteroids (ICS) may have their dose increased despite limited evidence of additional clinical benefits and increased risk of side effects. Dupilumab is a fully human monoclonal antibody that blocks the shared receptor component for interleukin-4 and -13, key and central drivers of type 2 inflammation underlying both asthma and CRSwNP. Here, we report the efficacy of dupilumab + medium-dose ICS vs omalizumab + high-dose ICS in patients with coexisting severe CRSwNP and uncontrolled asthma. Methods Phase 4 EVEREST (NCT04998604) evaluated the efficacy and safety of dupilumab vs omalizumab in patients ≥18 years old with severe CRSwNP and coexisting uncontrolled asthma (defined as 5-item Asthma Control Questionnaire (ACQ)-5 score ≥1.5). Patients were randomized 1:1 to dupilumab 300 mg every 2 weeks or omalizumab 75-600 mg every 2 or 4 weeks for 24 weeks. Estimated mean changes from baseline to Week 24 (95% CI) were evaluated in the dupilumab + medium-dose ICS vs omalizumab + high-dose ICS groups using the University of Pennsylvania Smell Identification Test (UPSIT; range 0-40, with higher scores indicating increased ability to differentiate between odorants; minimal clinically important difference [MCID] 8); pre-bronchodilator forced expiratory volume in 1 second (FEV1; MCID 0.15 L); and 7-item ACQ (ACQ-7; range 0-6, with higher scores indicating worse asthma control; MCID 0.5). Results In the dupilumab + medium-dose ICS (n = 52)/omalizumab + high-dose ICS (n = 29) groups, baseline mean (SD) UPSIT score was 10.77 (4.44)/10.66 (6.82), pre-bronchodilator FEV1 was 2.83 L (1.04)/2.44 L (0.86), and ACQ-7 was 2.80 (0.74)/3.08 (1.03). At Week 24, estimated mean change from baseline in UPSIT was 11.99 (95% CI: 9.26, 14.73) for dupilumab + medium-dose ICS and 2.44 (−1.15, 6.02) for omalizumab + high-dose ICS (Table). Dupilumab with medium-dose ICS also provided enhanced lung function and asthma control improvements vs omalizumab with high-dose ICS. At Week 24, the estimated mean change from baseline in pre-bronchodilator FEV1 was 0.32 L (0.16, 0.48) for dupilumab + medium-dose ICS and 0.10 L (−0.14, 0.35) for omalizumab + high-dose ICS. Estimated mean changes from baseline in ACQ-7 score at Week 24 were −2.03 (−2.29, −1.77) and −1.51 (−2.03, −1.00), respectively. Conclusion In patients with coexisting CRSwNP and uncontrolled asthma, dupilumab with medium-dose ICS provided greater improvements in smell differentiation, lung function, and asthma control than omalizumab with high-dose ICS. This abstract is funded by: This research was sponsored by Sanofi and Regeneron Pharmaceuticals Inc.