TY - JOUR
T1 - Prevalence of type 2 inflammatory signatures and efficacy of dupilumab in patients with chronic rhinosinusitis with nasal polyps from two phase 3 clinical trials
T2 - SINUS-24 and SINUS-52
AU - Bachert, Claus
AU - Khan, Asif H.
AU - Lee, Stella E.
AU - Hopkins, Claire
AU - Peters, Anju T.
AU - Fokkens, Wytske
AU - Praestgaard, Amy
AU - Radwan, Amr
AU - Nash, Scott
AU - Jacob-Nara, Juby A.
AU - Deniz, Yamo
AU - Rowe, Paul J.
N1 - Funding Information: Medical writing support was provided by Joseph Hodgson, PhD of Adelphi Group, Macclesfield, UK and funded by Sanofi and Regeneron Pharmaceuticals Inc. ClinicalTrials.gov identifiers: NCT02912468 and NCT02898454, in accordance with Good Publications Practice. Publisher Copyright: © 2023 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.
PY - 2023
Y1 - 2023
N2 - Background: This 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. Methods: Six 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). Results: At 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). Conclusion: Most 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.
AB - Background: This 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. Methods: Six 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). Results: At 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). Conclusion: Most 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.
KW - chronic rhinosinusitis
KW - medical therapy of chronic rhinosinusitis
KW - paranasal sinus diseases
KW - patient-reported outcome measure
UR - http://www.scopus.com/inward/record.url?scp=85168580965&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/alr.23249
DO - https://doi.org/10.1002/alr.23249
M3 - Article
C2 - 37548085
SN - 2042-6976
JO - International forum of allergy & rhinology
JF - International forum of allergy & rhinology
ER -