Prevalence of type 2 inflammatory signatures and efficacy of dupilumab in patients with chronic rhinosinusitis with nasal polyps from two phase 3 clinical trials: SINUS‐24 and SINUS‐52

Abstract

AbstractBackgroundThis post hoc analysis of the international SINUS‐24/‐52 trials (NCT02912468/NCT02898454) aimed to assess dupilumab efficacy in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) according to different definitions of type 2 inflammatory signature.MethodsSix definitions of type 2 inflammation were used: ≥150 eosinophils/μL or total immunoglobulin E (IgE) ≥100 IU/mL with a coexisting type 2 condition; ≥150 eosinophils/μL or total IgE ≥100 IU/mL; ≥150 eosinophils/μL; ≥250 eosinophils/μL or total IgE ≥100 IU/mL; coexisting asthma or ≥300 eosinophils/μL; presence of a coexisting type 2 condition. Odds ratios (ORs; dupilumab vs. placebo) for achieving clinically meaningful improvement (≥1 point) from baseline to week 24 (pooled SINUS‐24/‐52) and week 52 (SINUS‐52) were calculated for nasal polyp score (NPS; range 0–8), nasal congestion/obstruction score (NC; 0−3), and loss of smell score (LoS; 0−3).ResultsAt baseline (n = 724), most patients displayed a type 2 inflammatory signature across definitions (64.2%–95.3%). At week 24, ORs for clinically meaningful improvement ranged from 11.9 to 14.9 for NPS across type 2 definitions, 6.5–9.6 for NC, and 12.2–17.8 for LoS (all p < 0.0001). OR ranges were similar or greater at week 52: 19.0–36.6, 7.6–12.1, and 9.2–33.5, respectively (all p < 0.0001).ConclusionMost patients with CRSwNP in the SINUS study had type 2 inflammation. Dupilumab demonstrated robust efficacy across definitions of type 2 inflammation, consistent with its profile as an inhibitor of Interleukin‐4 and Interleukin‐13 signaling, key and central drivers of type 2 inflammation in CRSwNP.KEY POINTS This study assessed type 2 inflammation prevalence and dupilumab efficacy in chronic rhinosinusitis with nasal polyps according to algorithm‐defined type 2 inflammation Dupilumab efficacy was similar across all type 2 definitions