Dupilumab Improves Outcomes in Chronic Rhinosinusitis with Nasal Polyps Patients with a Type 2 Inflammatory Signature Irrespective of Definition

Introduction Chronic rhinosinusitis with nasal polyps (CRSwNP) is a predominantly type 2 (T2) inflammatory disease. The aim of this post hoc analysis of the SINUS-24 and SINUS-52 trials (NCT02912468/NCT02898454) was to assess dupilumab efficacy in CRSwNP patients with a T2 signature defined according to previously proposed algorithms.

Methods T2 definitions used were 1) ≥150 eosinophils/μL or total IgE ≥100 IU/mL or any coexisting T2 condition; 2) ≥150 eosinophils/μL or total IgE ≥100 IU/mL; 3) ≥150 eosinophils/μL (GINA); 4) ≥250 eosinophils/μL or total IgE ≥100 IU/mL (EPOS); 5) asthma or ≥300 eosinophils/μL (EUFOREA); 6) any coexisting T2 condition. Odds ratios (ORs; dupilumab vs placebo) of achieving clinically meaningful improvements (≥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).

Results ORs (95% confidence intervals) at Week 24 across the six T2 definitions ranged from 11.4 (7.4, 17.5) to 14.9 (9.4, 23.7) for NPS; 6.5 (4.5, 9.3) to 9.6 (6.0, 15.3) for NC; and 12.2 (8.0, 18.8) to 17.8 (10.6, 30.0) for LoS (all P<0.0001). Improvements were maintained or enhanced at Week 52.

Conclusion  Consistent with its profile as an inhibitor of IL-4/IL-13 signaling, key and central drivers of T2 inflammation, dupilumab showed robust efficacy across definitions of T2 inflammation in patients with CRSwNP.

Sanofi and Regeneron Pharmaceuticals, Inc.

Publication History

Article published online:
12 May 2023