Abstract Rationale Loss of smell is a hallmark symptom of chronic rhinosinusitis with nasal polyps (CRSwNP) that is commonly associated with severe type 2 inflammation and comorbid asthma. It is underrecognized in patients with coexisting asthma and is detectable through screening. Dupilumab and omalizumab are both approved for the treatment of inadequately controlled CRSwNP and uncontrolled moderate-to-severe asthma. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and -13, key and central drivers of type 2 inflammation in multiple diseases, whereas omalizumab only targets IgE. EVEREST (NCT04998604) was a 24-week, randomized, double-blind, phase 4 study comparing dupilumab with omalizumab in adults with severe CRSwNP and coexisting asthma. This post hoc analysis evaluated the efficacy of dupilumab vs omalizumab on clinical outcomes in patients with severe CRSwNP and uncontrolled asthma who were anosmic at baseline. Methods Patients aged ≥18 years with severe CRSwNP and uncontrolled asthma (defined as 5-item Asthma Control Questionnaire ACQ-5 score ≥1.5) received background mometasone furoate nasal spray and were randomized 1:1 to receive dupilumab 300 mg every 2 weeks or omalizumab 75-600 mg every 2 or 4 weeks. The anosmia subgroup included patients with baseline University of Pennsylvania Smell Identification Test score ≤18 (range 0-40; higher scores indicate increased ability to differentiate odorants). At Week 24, we evaluated estimated mean changes from baseline in nasal polyp score (NPS; range 0-8; greater scores indicate larger nasal polyps and greater nasal obstruction; minimal clinically important difference MCID 1), in pre-bronchodilator forced expiratory volume in 1 second (FEV₁) (MCID 0.15 L), and in ACQ-7 score (range 0-6; MCID 0.5). Results Among 355 patients with CRSwNP and asthma in EVEREST evaluated for anosmia, 322 (90.7%) were anosmic at baseline and therefore included in this analysis. Of these, 165 received dupilumab and 157 received omalizumab. At Week 24, dupilumab vs omalizumab significantly reduced NPS (LS mean difference 95% CI: -1.75 -2.11, -1.38; P0.0001), improved pre-bronchodilator FEV1 (0.18 L 0.07, 0.29; P0.001), and reduced ACQ-7 score (-0.53 -0.71, -0.35; P0.0001) (Table). Conclusion In patients with severe CRSwNP and asthma who were anosmic at baseline, dupilumab produced significantly greater and clinically meaningful improvements in nasal polyp burden, lung function, and asthma control than omalizumab over 24 weeks. These results highlight the role of type 2 cytokine blockade in achieving comprehensive control of upper and lower airway disease in patients with CRSwNP and asthma. This abstract is funded by: This research was sponsored by Sanofi and Regeneron Pharmaceuticals.
Lipworth et al. (Fri,) studied this question.