Efficacy of Dupilumab in Patients with Chronic Rhinosinusitis with Nasal Polyps and Allergic Rhinitis

RATIONALE: Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disease of the nasal and paranasal sinuses.Allergic rhinitis (AR) is a type 2 inflammatory condition common in patients with CRSwNP, and may be associated with poorer CRSwNP outcomes compared with patients without AR.Dupilumab, a fully human monoclonal antibody, blocks interleukin (IL)-4 receptor-α, the shared receptor component for IL-4 and IL-13, which are key and central drivers of type 2 inflammation.This post hoc analysis investigated the efficacy of dupilumab for the treatment of patients with CRSwNP with and without AR using pooled data from the SINUS-24 (NCT02912468) and SINUS-52 (NCT02898454) phase 3 studies.METHODS: Adults with CRSwNP were randomized to receive either placebo or subcutaneous dupilumab 300 mg every 2 weeks for 24 weeks (SINUS-24) or 52 weeks (SINUS-52).AR diagnosis was ascertained by self-reported medical history.Pooled data from the first 24 weeks of treatment are presented.The mean change from baseline to Week 24 was determined for nasal congestion (NC) score, nasal polyp score (NPS), University of Pennsylvania Smell Identification Test (UPSIT) score, loss of smell score (LoSS), and rhinosinusitis visual analog scale (VAS) score, and total serum immunoglobulin E (IgE).Least squares (LS) mean difference vs placebo was determined for each endpoint for subgroups of patients with and without AR.RESULTS: The pooled intent-to-treat population of placebo and dupilumab groups included 338/724 patients (46.7%) with AR at baseline and 386/724 without (53.3%).Baseline characteristics were similar between patients with and without comorbid AR.Significant improvements in both clinical and symptom scores were demonstrated for dupilumab compared with placebo in patients with CRSwNP regardless of AR status (Table ).Reductions in total IgE were observed with dupilumab among patients with AR and those without AR (Table ).CONCLUSIONS: Dupilumab demonstrated significant improvements in NPS, NC, UPSIT, LoSS, and rhinosinusitis VAS scores vs placebo in patients with severe CRSwNP irrespective of comorbid AR, a common subgroup of patients often associated with poorer CRSwNP outcomes.Reductions in total IgE with dupilumab in patients with CRSwNP and AR were substantial, consistent with results among patients without AR.