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

被引：13

作者：

Bachert, Claus ^{[1
,2
,3
,14
]}

Khan, Asif H. H. ^{[4
]}

Lee, Stella E. E. ^{[5
]}

Hopkins, Claire ^{[6
]}

Peters, Anju T. T. ^{[7
,8
]}

Fokkens, Wytske ^{[9
]}

Praestgaard, Amy ^{[10
]}

Radwan, Amr ^{[11
]}

Nash, Scott ^{[12
]}

Jacob-Nara, Juby A. A. ^{[13
]}

Deniz, Yamo ^{[12
]}

Rowe, Paul J. J. ^{[13
]}

机构：

[1] Univ Hosp Munster, Munster, Germany

[2] Sun Yat Sen Univ, Affiliated Hosp 1, Guangzhou, Peoples R China

[3] Stockholm Univ, Karolinska Hosp, Stockholm, Sweden

[4] Sanofi, Chilly Mazarin, France

[5] Harvard Med Sch, Brigham & Womens Hosp, Div Otolaryngol Head & Neck Surg, Boston, MA USA

[6] Guys & St Thomas Hosp, London, England

[7] Northwestern Univ, Feinberg Sch Med, Allergy Immunol Div, Chicago, IL USA

[8] Northwestern Univ, Sinus & Allergy Ctr, Feinberg Sch Med, Chicago, IL USA

[9] Acad Med Ctr, Amsterdam, Netherlands

[10] Sanofi, Cambridge, MA USA

[11] Regeneron Pharmaceut Inc, Uxbridge, England

[12] Regeneron Pharmaceut Inc, Tarrytown, NY USA

[13] Sanofi, Bridgewater, NJ USA

[14] Univ Hosp Munster, Dept Otorhinolaryngol Head & Neck Surg, Munster, Germany

来源：

INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY | 2024年 / 14卷 / 03期

关键词：

chronic rhinosinusitis; medical therapy of chronic rhinosinusitis; paranasal sinus diseases; patient-reported outcome measure;

D O I：

10.1002/alr.23249

中图分类号：

R76 [耳鼻咽喉科学];

学科分类号：

100213 ;

摘要：

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

引用

页码：668 / 678

页数：11

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