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

BackgroundThis 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: & GE;150 eosinophils/& mu;L or total immunoglobulin E (IgE) & GE;100 IU/mL with a coexisting type 2 condition; & GE;150 eosinophils/& mu;L or total IgE & GE;100 IU/mL; & GE;150 eosinophils/& mu;L; & GE;250 eosinophils/& mu;L or total IgE & GE;100 IU/mL; coexisting asthma or & GE;300 eosinophils/& mu;L; presence of a coexisting type 2 condition. Odds ratios (ORs; dupilumab vs. placebo) for achieving clinically meaningful improvement (& GE;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 POINTSThis study assessed type 2 inflammation prevalence and dupilumab efficacy in chronic rhinosinusitis with nasal polyps according to algorithm-defined type 2 inflammationDupilumab efficacy was similar across all type 2 definitions