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
© 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..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
International forum of allergy & rhinology - 14(2024), 3 vom: 27. März, Seite 668-678 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bachert, Claus [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 12.03.2024 Date Revised 12.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/alr.23249 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM360477585 |
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| 245 | 1 | 0 | |a Prevalence of type 2 inflammatory signatures and efficacy of dupilumab in patients with chronic rhinosinusitis with nasal polyps from two phase 3 clinical trials |b SINUS-24 and SINUS-52 |
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| 500 | |a Date Revised 12.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 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. | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a chronic rhinosinusitis | |
| 650 | 4 | |a medical therapy of chronic rhinosinusitis | |
| 650 | 4 | |a paranasal sinus diseases | |
| 650 | 4 | |a patient-reported outcome measure | |
| 650 | 7 | |a dupilumab |2 NLM | |
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| 700 | 1 | |a Peters, Anju T |e verfasserin |4 aut | |
| 700 | 1 | |a Fokkens, Wytske |e verfasserin |4 aut | |
| 700 | 1 | |a Praestgaard, Amy |e verfasserin |4 aut | |
| 700 | 1 | |a Radwan, Amr |e verfasserin |4 aut | |
| 700 | 1 | |a Nash, Scott |e verfasserin |4 aut | |
| 700 | 1 | |a Jacob-Nara, Juby A |e verfasserin |4 aut | |
| 700 | 1 | |a Deniz, Yamo |e verfasserin |4 aut | |
| 700 | 1 | |a Rowe, Paul J |e verfasserin |4 aut | |
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