Dupilumab improved objective and patient-reported outcomes in patients with chronic rhinosinusitis with nasal polyps and complete nasal obstruction

Abstract

Aim: The impact of complete bilateral nasal obstruction [nasal polyp score (NPS)=8/8] on treatment outcomes in chronic rhinosinusitis with nasal polyps (CRSwNP) is unclear. This post hoc analysis assessed disease burden and dupilumab efficacy in patients with severe CRSwNP and baseline NPS=8 in SINUS-24/-52 (NCT02912468/NCT02898454). Methods: Efficacy outcomes assessed: NPS, peak nasal inspiratory flow (PNIF), Lund-Mackay computed tomography (LMK-CT), nasal congestion/obstruction (NC), loss of smell (LoS), rhinosinusitis visual analog scale (rhino-VAS), University of Pennsylvania Smell Identification Test (UPSIT), 22-item Sinonasal Outcome Test (SNOT-22) in patients receiving dupilumab 300 mg or placebo every 2 weeks. Responder analyses evaluated clinically meaningful improvements [≥ 1 (NPS, NC, LoS); ≥ 5 (LMK-CT); ≥ 8 (UPSIT); ≥ 8.9 (SNOT-22); ≥ 20 L/min (PNIF)]. Results: Ninety-eight patients were included [59% prior NP surgery, 84% systemic corticosteroids (SCS) use in the previous 2 years, 60% coexisting asthma, 91% anosmic, 97% impaired nasal airflow]. Least squares (LS) mean differences [dupilumab vs. placebo (95% CI)] in change from baseline at week (W) 24: NPS, −2.04 (−2.67, −1.40); PNIF, 65.9 (39.4, 92.4) L/min; LMK-CT, −4.97 (−6.50, −3.44); NC, −1.30 (−1.72, −0.89); LoS, −0.96 (−1.39, −0.54); Rhino-VAS, −3.37 (−4.67, −2.07); UPSIT, 8.55 (4.91, 12.20); SNOT-22, −25.3 (−34.1, −16.4) (all P < 0.0001). For all outcomes, significantly greater proportions of dupilumab vs. placebo patients achieved clinically meaningful improvements at W24. Fewer dupilumab vs. placebo patients required SCS and/or surgery through W24 (11.8% vs. 36.7%; P=0.0005). Efficacy outcomes were similar at W52 (SINUS-52; n=39) with P values vs. placebo of < 0.0001 for NPS and NC; 0.0002 for LMK-CT; 0.0031 for LoS; 0.0014 for rhino-VAS; 0.0013 for UPSIT; 0.0012 for SNOT-22. Conclusions: In patients with CRSwNP with complete bilateral nasal obstruction, dupilumab treatment resulted in clinically significant improvements in NPS, LMK-CT, PNIF, symptoms, and health-related quality of life.

Keywords

Type 2 inflammation / nasal polyposis / nasal inspiratory flow / nasal polyp score / biologics

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