Jorge F Maspero1, Constance H Katelaris2, William W Busse3, Mario Castro4, Jonathan Corren5, Bradley E Chipps6, Anju T Peters7, Ian D Pavord8, Linda B Ford9, Lawrence Sher10, Klaus F Rabe11, Megan S Rice12, Paul Rowe13, Yufang Lu14, Sivan Harel14, Alexandre Jagerschmidt15, Asif H Khan15, Siddhesh Kamat14, Gianluca Pirozzi13, Nikhil Amin14, Marcella Ruddy14, Neil M H Graham14, Leda P Mannent15, Ariel Teper13. 1. Fundación CIDEA, Buenos Aires, Argentina. Electronic address: jorge.maspero@fundacioncidea.org.ar. 2. Campbelltown Hospital, Campbelltown, NSW, Australia; Western Sydney University, Sydney, NSW, Australia. 3. University of Wisconsin School of Medicine and Public Health, Madison, Wis. 4. Washington University School of Medicine, Saint Louis, Mo. 5. David Geffen School of Medicine at UCLA, Los Angeles, Calif. 6. Capital Allergy and Respiratory Disease Center, Sacramento, Calif. 7. Division of Allergy-Immunology and the Sinus and Allergy Center, Feinberg School of Medicine, Northwestern University, Chicago, Ill. 8. University of Oxford, Oxford, United Kingdom. 9. Asthma & Allergy Center, Bellevue, Neb. 10. Peninsula Research Associates, Rolling Hills Estates, Calif. 11. LungenClinic Grosshansdorf, Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany; Christian-Albrechts-University of Kiel, Member of the German Center for Lung Research (DZL), Kiel, Germany. 12. Sanofi Genzyme, Cambridge, Mass. 13. Sanofi, Bridgewater, NJ. 14. Regeneron Pharmaceuticals, Inc., Tarrytown, NY. 15. Sanofi, Chilly-Mazarin, France.
Abstract
BACKGROUND:Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for IL-4 and IL-13 signaling, key drivers of type 2 inflammation. In the phase 3 study (NCT02414854), add-on dupilumab 200 mg/300 mg every 2 weeks, versus placebo, significantly reduced severe asthma exacerbations and improved pre-bronchodilator forced expiratory volume in 1 second (FEV1) and quality-of-life measures in patients with uncontrolled, moderate-to-severe asthma, with greater efficacy observed in those with a high baseline type 2 phenotype. OBJECTIVE: To assess the efficacy and safety of dupilumab in patients with uncontrolled, moderate-to-severe asthma with or without self-reported comorbid chronic rhinosinusitis (CRS or non-CRS). METHODS: Comorbid CRS was self-reported by patients using an e-diary. Annualized severe exacerbation rates, changes from baseline in pre- and post-bronchodilator FEV1, patient-reported outcomes, type 2 biomarkers, and safety were assessed. RESULTS: CRS was self-reported by 382 of 1902 (20.1%) patients. Dupilumab 200 mg/300 mg reduced annualized severe exacerbation rates by 63%/61%, respectively, in patients with CRS, and by 42%/40% in patients without CRS (all P < .001 vs placebo). Dupilumab also improved lung function and patient-reported asthma control and quality of life, and suppressed type 2 biomarkers versus placebo in both subgroups. Clinical responses were rapid, with near-maximal responses observed at the earliest measured time points and sustained at week 52. Improvements observed in the CRS subgroup were similar to or numerically greater than those in the non-CRS subgroup. CONCLUSION:Dupilumab showed efficacy and was generally well tolerated in patients with uncontrolled, moderate-to-severe asthma with or without CRS.
RCT Entities:
BACKGROUND:Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for IL-4 and IL-13 signaling, key drivers of type 2 inflammation. In the phase 3 study (NCT02414854), add-on dupilumab 200 mg/300 mg every 2 weeks, versus placebo, significantly reduced severe asthma exacerbations and improved pre-bronchodilator forced expiratory volume in 1 second (FEV1) and quality-of-life measures in patients with uncontrolled, moderate-to-severe asthma, with greater efficacy observed in those with a high baseline type 2 phenotype. OBJECTIVE: To assess the efficacy and safety of dupilumab in patients with uncontrolled, moderate-to-severe asthma with or without self-reported comorbid chronic rhinosinusitis (CRS or non-CRS). METHODS: Comorbid CRS was self-reported by patients using an e-diary. Annualized severe exacerbation rates, changes from baseline in pre- and post-bronchodilator FEV1, patient-reported outcomes, type 2 biomarkers, and safety were assessed. RESULTS: CRS was self-reported by 382 of 1902 (20.1%) patients. Dupilumab 200 mg/300 mg reduced annualized severe exacerbation rates by 63%/61%, respectively, in patients with CRS, and by 42%/40% in patients without CRS (all P < .001 vs placebo). Dupilumab also improved lung function and patient-reported asthma control and quality of life, and suppressed type 2 biomarkers versus placebo in both subgroups. Clinical responses were rapid, with near-maximal responses observed at the earliest measured time points and sustained at week 52. Improvements observed in the CRS subgroup were similar to or numerically greater than those in the non-CRS subgroup. CONCLUSION:Dupilumab showed efficacy and was generally well tolerated in patients with uncontrolled, moderate-to-severe asthma with or without CRS.
Authors: Andrew Gallagher; Michaela Edwards; Parameswaran Nair; Stewart Drew; Aashish Vyas; Rashmi Sharma; Paul A Marsden; Ran Wang; David Jw Evans Journal: Cochrane Database Syst Rev Date: 2021-10-19
Authors: Jennifer D Hamilton; Sivan Harel; Brian N Swanson; William Brian; Zhen Chen; Megan S Rice; Nikhil Amin; Marius Ardeleanu; Allen Radin; Brad Shumel; Marcella Ruddy; Naimish Patel; Gianluca Pirozzi; Leda Mannent; Neil M H Graham Journal: Clin Exp Allergy Date: 2021-06-26 Impact factor: 5.018