ATS 2021 will feature presentations of original research from accepted abstracts. Mini Symposia and Thematic Poster Sessions are abstract based sessions.
Please use the form below to browse scientific abstracts and case reports accepted for ATS 2021. Abstracts presented at the ATS 2021 will be published in the Online Abstract Issue of the American Journal of Respiratory and Critical Care Medicine, Volume 203, May 3, 2021.
Search Tips:
- Use the keyword search to search by keyword or author's name.
- Filter your search results by selecting the checkboxes that apply.
- Click on "Clear" to clear the form and start a new search. .
Search results will display below the form.
Rapid and Sustained Effects of Dupilumab in Patients with Severe Chronic Rhinosinusitis with Nasal Polyps: Analysis of the SINUS-24 and SINUS-52 Phase 3 Trails
Session Title
TP6 - TP006 CLINICAL STUDIES OF ALLERGIC AIRWAY DISEASES, LUPUS, AND EOSINOPHILIC DISEASES
Abstract
A1345 - Rapid and Sustained Effects of Dupilumab in Patients with Severe Chronic Rhinosinusitis with Nasal Polyps: Analysis of the SINUS-24 and SINUS-52 Phase 3 Trails
Author Block: P. W. Hellings1, A. Peters2, A. M. Chaker3, E. Heffler4, H. Zhang5, N. Daizadeh6, S. Nash5, A. H. Khan7, S. Siddiqui5, J. A. Jacob-Nara6; 1University Hospitals Leuven, Leuven, Belgium, 2Feinberg School of Medicine, Northwestern University, Chicago, IL, United States, 3Technical University of Munich, Klinikum rechts der Isar, Department of Otolaryngology and ZAUM, Munich, Germany, 4Humanitas Clinical and Research Center IRCCS, Rozzano, Milan, Italy, 5Regeneron Pharmaceuticals, Inc., Tarrytown, NY, United States, 6Sanofi, Cambridge, NJ, United States, 7Sanofi, Chilly Mazarin, France.
RATIONALE: In the Phase 3 SINUS-24 (NCT02912468) and SINUS-52 (NCT02898454) studies in adults with severe chronic rhinosinusitis with nasal polyps (CRSwNP), dupilumab significantly improved endoscopic, radiologic, clinical, and quality-of-life outcomes vs placebo, and was generally well tolerated. We report the onset and continued effects on subjective and objective measures of CRSwNP from the SINUS-24 and SINUS-52 studies overall and by patient-reported history of asthma, non-steroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD), sinonasal surgery, and allergic rhinitis (AR).
METHODS: Patients were randomized 1:1 in SINUS-24 to double-blind treatment with subcutaneous dupilumab 300 mg or placebo every 2 weeks (q2w) for 24 weeks, and 1:1:1 in SINUS-52 to either dupilumab 300 mg q2w for 52 weeks, dupilumab 300 mg q2w for 24 weeks followed by every 4 weeks (q4w) to 52 weeks, or placebo. Results are presented for placebo and dupilumab 300 mg q2w (pooled to Week 24 and SINUS-52 to Week 52). Loss of smell symptom score (LoSS; 0−3), nasal congestion (NC; 0−3), and total symptom scores (TSS; 0−9) were assessed daily by eDiary. Peak nasal inspiratory flow (PNIF) was assessed daily to Week 24 and q4w thereafter. University of Pennsylvania Smell Identification Test (UPSIT), nasal polyp score (NPS), and 22-item Sino-Nasal Outcomes Test (SNOT-22) were assessed at scheduled visits. P values are presented for prespecified analyses and nominal P values for post-hoc analyses.
RESULTS: 724 patients were randomized. Mean duration of CRSwNP was 11 years (SD 9). Improvements with dupilumab emerged within the first week in all daily assessed measures: LS mean differences vs placebo emerged by Day 3 for LoSS (−0.07 [95% CI −0.12, −0.02]), Day 2 for NC (−0.07 [−0.13, −0.01]), Day 2 for TSS (−0.14 [−0.27, −0.02]), and Day 4 for PNIF (5.0 [1.8, 8.1] L/min); all nominal P <0.05. Improvements with dupilumab were sustained and increased through Week 52. LS mean differences vs placebo [95% CI] at Week 52 in SINUS-52 were: LoSS −1.10 [−1.31, −0.89], NC −0.98 [−1.17, −0.79], TSS −2.85 [−3.35, −2.35], UPSIT 10.3 [8.5, 12.1], NPS −2.40 [−2.77, −2.02], SNOT-22 −21.0 [−25.0, −16.9]; all P <0.0001; and PNIF 45.8 [36.5, 55.2] L/min; nominal P < 0.0001. Improvements with dupilumab were observed regardless of asthma (Figure), NSAID-ERD, prior surgery, or AR.
CONCLUSIONS: Dupilumab exhibited rapid onset of action as early as 2−4 days, with improvements across symptoms, regardless of history of asthma, NSAID-ERD, AR, or sinonasal surgery. Improvements were continuous and sustained to 52 weeks.
Author Block: P. W. Hellings1, A. Peters2, A. M. Chaker3, E. Heffler4, H. Zhang5, N. Daizadeh6, S. Nash5, A. H. Khan7, S. Siddiqui5, J. A. Jacob-Nara6; 1University Hospitals Leuven, Leuven, Belgium, 2Feinberg School of Medicine, Northwestern University, Chicago, IL, United States, 3Technical University of Munich, Klinikum rechts der Isar, Department of Otolaryngology and ZAUM, Munich, Germany, 4Humanitas Clinical and Research Center IRCCS, Rozzano, Milan, Italy, 5Regeneron Pharmaceuticals, Inc., Tarrytown, NY, United States, 6Sanofi, Cambridge, NJ, United States, 7Sanofi, Chilly Mazarin, France.
RATIONALE: In the Phase 3 SINUS-24 (NCT02912468) and SINUS-52 (NCT02898454) studies in adults with severe chronic rhinosinusitis with nasal polyps (CRSwNP), dupilumab significantly improved endoscopic, radiologic, clinical, and quality-of-life outcomes vs placebo, and was generally well tolerated. We report the onset and continued effects on subjective and objective measures of CRSwNP from the SINUS-24 and SINUS-52 studies overall and by patient-reported history of asthma, non-steroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD), sinonasal surgery, and allergic rhinitis (AR).
METHODS: Patients were randomized 1:1 in SINUS-24 to double-blind treatment with subcutaneous dupilumab 300 mg or placebo every 2 weeks (q2w) for 24 weeks, and 1:1:1 in SINUS-52 to either dupilumab 300 mg q2w for 52 weeks, dupilumab 300 mg q2w for 24 weeks followed by every 4 weeks (q4w) to 52 weeks, or placebo. Results are presented for placebo and dupilumab 300 mg q2w (pooled to Week 24 and SINUS-52 to Week 52). Loss of smell symptom score (LoSS; 0−3), nasal congestion (NC; 0−3), and total symptom scores (TSS; 0−9) were assessed daily by eDiary. Peak nasal inspiratory flow (PNIF) was assessed daily to Week 24 and q4w thereafter. University of Pennsylvania Smell Identification Test (UPSIT), nasal polyp score (NPS), and 22-item Sino-Nasal Outcomes Test (SNOT-22) were assessed at scheduled visits. P values are presented for prespecified analyses and nominal P values for post-hoc analyses.
RESULTS: 724 patients were randomized. Mean duration of CRSwNP was 11 years (SD 9). Improvements with dupilumab emerged within the first week in all daily assessed measures: LS mean differences vs placebo emerged by Day 3 for LoSS (−0.07 [95% CI −0.12, −0.02]), Day 2 for NC (−0.07 [−0.13, −0.01]), Day 2 for TSS (−0.14 [−0.27, −0.02]), and Day 4 for PNIF (5.0 [1.8, 8.1] L/min); all nominal P <0.05. Improvements with dupilumab were sustained and increased through Week 52. LS mean differences vs placebo [95% CI] at Week 52 in SINUS-52 were: LoSS −1.10 [−1.31, −0.89], NC −0.98 [−1.17, −0.79], TSS −2.85 [−3.35, −2.35], UPSIT 10.3 [8.5, 12.1], NPS −2.40 [−2.77, −2.02], SNOT-22 −21.0 [−25.0, −16.9]; all P <0.0001; and PNIF 45.8 [36.5, 55.2] L/min; nominal P < 0.0001. Improvements with dupilumab were observed regardless of asthma (Figure), NSAID-ERD, prior surgery, or AR.
CONCLUSIONS: Dupilumab exhibited rapid onset of action as early as 2−4 days, with improvements across symptoms, regardless of history of asthma, NSAID-ERD, AR, or sinonasal surgery. Improvements were continuous and sustained to 52 weeks.
