Efficacy and Safety of Dupilumab in Patients with Chronic Rhinosinusitis with Nasal Polyps: Results from the Randomized Phase 3 Sinus-24 Study

Abstract

Dupilumab, a human IL-4R-α mAb inhibiting IL-4 and IL-13, key drivers of type 2-mediated inflammation, is approved for uncontrolled moderate-to-severe atopic dermatitis in adults and in the USA for patients aged ≥12 years with moderate-to-severe eosinophilic or oral corticosteroid-dependent asthma. In a phase 2a study, dupilumab improved endoscopic, radiologic, clinical, and patient-reported outcomes in chronic rhinosinusitis with nasal polyps (CRSwNP) patients. For the first time we report results from a phase 3 dupilumab study (SINUS-24; NCT02912468) in severe CRSwNP patients (with/without comorbid asthma) on daily intra-nasal mometasone furoate (MFNS). Adults with CRSwNP previously treated with systemic corticosteroids (SCS) and/or surgery (n = 276) were randomized 1:1 to subcutaneous dupilumab 300mg or placebo every 2 weeks for 24 weeks. Outcomes included change from baseline to Week 24 in nasal polyp score (NPS), patient-reported nasal congestion (NC), CT Lund-Mackay (LMK), UPSIT smell test, SNOT-22, FEV1, and ACQ-6 scores. Mean [SD] baseline values were comparable in dupilumab/placebo for NPS (5.64 [1.23] / 5.86 [1.31]), NC (2.26[0.57]/2.45[0.55]), LMK (18.55 [4.55] / 19.55 [4.26]), UPSIT (14.68 [8.66] / 14.44[8.31]), and SNOT-22 (48.00 [20.16] / 50.87[20.22]). Dupilumab significantly (P<0.0001) improved NPS (−2.06), NC (−0.89), LMK (−7.44), UPSIT (+10.56), and SNOT-22 (−21.12) from baseline to Week 24 (LS-mean differences vs placebo). Dupilumab treatment reduced SCS use/NP surgery (P<0.001), and in comorbid asthma patients (58.3%) improved lung function (FEV1; P<0.001) and asthma control (ACQ-6; P<0.0001). The most common adverse event occurring at higher frequency with dupilumab was epistaxis (7.7% vs 3.0% placebo). Add-on dupilumab to MFNS significantly improved endoscopic, radiologic, clinical, and patient-reported sino-nasal outcomes, and asthma outcome measures in severe CRSwNP patients, and was well-tolerated.