PMID- 37548085
OWN - NLM
STAT- MEDLINE
DCOM- 20240312
LR  - 20240312
IS  - 2042-6984 (Electronic)
IS  - 2042-6976 (Linking)
VI  - 14
IP  - 3
DP  - 2024 Mar
TI  - 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.
PG  - 668-678
LID - 10.1002/alr.23249 [doi]
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/muL or total immunoglobulin E 
      (IgE) >/=100 IU/mL with a coexisting type 2 condition; >/=150 eosinophils/muL or total 
      IgE >/=100 IU/mL; >/=150 eosinophils/muL; >/=250 eosinophils/muL or total IgE >/=100 IU/mL; 
      coexisting asthma or >/=300 eosinophils/muL; 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.
CI  - (c) 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.
FAU - Bachert, Claus
AU  - Bachert C
AD  - University Hospital of Munster, Munster, Germany.
AD  - Sun Yat-sen University, The First Affiliated Hospital, Guangzhou, China.
AD  - Karolinska Hospital, Stockholm University, Stockholm, Sweden.
FAU - Khan, Asif H
AU  - Khan AH
AD  - Sanofi, Chilly Mazarin, France.
FAU - Lee, Stella E
AU  - Lee SE
AD  - Division of Otolaryngology - Head and Neck Surgery, Brigham and Women's Hospital, 
      Harvard Medical School, Boston, Massachusetts, USA.
FAU - Hopkins, Claire
AU  - Hopkins C
AUID- ORCID: 0000-0003-3993-1569
AD  - Guy's and St Thomas' Hospitals, London, UK.
FAU - Peters, Anju T
AU  - Peters AT
AD  - Allergy-Immunology Division and the Sinus and Allergy Center, Feinberg School of 
      Medicine, Northwestern University, Chicago, Illinois, USA.
FAU - Fokkens, Wytske
AU  - Fokkens W
AD  - Academic Medical Center, Amsterdam, The Netherlands.
FAU - Praestgaard, Amy
AU  - Praestgaard A
AD  - Sanofi, Cambridge, Massachusetts, USA.
FAU - Radwan, Amr
AU  - Radwan A
AD  - Regeneron Pharmaceuticals Inc., Uxbridge, UK.
FAU - Nash, Scott
AU  - Nash S
AD  - Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
FAU - Jacob-Nara, Juby A
AU  - Jacob-Nara JA
AD  - Sanofi, Bridgewater, New Jersey, USA.
FAU - Deniz, Yamo
AU  - Deniz Y
AD  - Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
FAU - Rowe, Paul J
AU  - Rowe PJ
AD  - Sanofi, Bridgewater, New Jersey, USA.
LA  - eng
GR  - Sanofi/
GR  - NCT02912468/Regeneron Pharmaceuticals Inc. ClinicalTrials.gov identifiers/
GR  - NCT02898454/Regeneron Pharmaceuticals Inc. ClinicalTrials.gov identifiers/
PT  - Journal Article
DEP - 20230822
PL  - United States
TA  - Int Forum Allergy Rhinol
JT  - International forum of allergy & rhinology
JID - 101550261
RN  - 420K487FSG (dupilumab)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 0 (Antibodies, Monoclonal, Humanized)
SB  - IM
MH  - Humans
MH  - *Nasal Polyps/drug therapy/complications
MH  - Prevalence
MH  - *Rhinosinusitis
MH  - *Rhinitis/drug therapy/epidemiology/complications
MH  - *Sinusitis/drug therapy/epidemiology/complications
MH  - Inflammation
MH  - Chronic Disease
MH  - Immunoglobulin E
MH  - *Antibodies, Monoclonal, Humanized
OTO - NOTNLM
OT  - chronic rhinosinusitis
OT  - medical therapy of chronic rhinosinusitis
OT  - paranasal sinus diseases
OT  - patient-reported outcome measure
EDAT- 2023/08/07 06:41
MHDA- 2024/03/12 06:42
CRDT- 2023/08/07 05:30
PHST- 2023/07/27 00:00 [revised]
PHST- 2023/01/18 00:00 [received]
PHST- 2023/07/31 00:00 [accepted]
PHST- 2024/03/12 06:42 [medline]
PHST- 2023/08/07 06:41 [pubmed]
PHST- 2023/08/07 05:30 [entrez]
AID - 10.1002/alr.23249 [doi]
PST - ppublish
SO  - Int Forum Allergy Rhinol. 2024 Mar;14(3):668-678. doi: 10.1002/alr.23249. Epub 
      2023 Aug 22.