TY - JOUR
T1 - Dupilumab Efficacy in Uncontrolled, Moderate-to-Severe Asthma with Self-Reported Chronic Rhinosinusitis
AU - Maspero, Jorge F.
AU - Katelaris, Constance H.
AU - Busse, William W.
AU - Castro, Mario
AU - Corren, Jonathan
AU - Chipps, Bradley E.
AU - Peters, Anju T.
AU - Pavord, Ian D.
AU - Ford, Linda B.
AU - Sher, Lawrence
AU - Rabe, Klaus F.
AU - Rice, Megan S.
AU - Rowe, Paul
AU - Lu, Yufang
AU - Harel, Sivan
AU - Jagerschmidt, Alexandre
AU - Khan, Asif H.
AU - Kamat, Siddhesh
AU - Pirozzi, Gianluca
AU - Amin, Nikhil
AU - Ruddy, Marcella
AU - Graham, Neil M.H.
AU - Mannent, Leda P.
AU - Teper, Ariel
N1 - Funding Information:
This research is sponsored by Sanofi and Regeneron Pharmaceuticals.Conflicts of interest: J. F. Maspero is a consultant at AstraZeneca, Sanofi, and Teva; receives speaker fees from GSK, Menarini, Novartis, and Uriach; and research grants from Novartis. C. H. Katelaris is a principal investigator of the dupilumab asthma phase 2b (NCT01854047) and 3 (NCT02414854) studies. W. W. Busse is a consultant at Regeneron Pharmaceuticals, Inc., and Sanofi. M. Castro receives research support from American Lung Association, AstraZeneca, Boehringer Ingelheim, Chiesi, National Institutes of Health, Novartis, Patient-Centered Outcomes Research Institute, and Sanofi; is a consultant at 4D Pharma, Aviragen Therapeutics, Boston Scientific, Genentech, Nuvaira Inc., Sanofi, Teva, Therabron Therapeutics, Theravance, Vectura, and VIDA Pharma; receives speakers' honoraria from AstraZeneca, Boehringer Ingelheim, Boston Scientific, Genentech, Regeneron Pharmaceuticals, Inc., Sanofi, and Teva; and royalties from Elsevier. J. Corren receives research grants from and is a consultant at AstraZeneca, Genentech, Novartis, Regeneron Pharmaceuticals, Inc., and Sanofi; and receives speaker fees from AstraZeneca, Genentech, and Novartis. B. E. Chipps is a consultant at AstraZeneca, Boehringer Ingelheim, Circassia, Genentech, Novartis, Sanofi, Regeneron Pharmaceuticals, Inc., and Teva; and in speakers' bureau at AstraZeneca, Boehringer Ingelheim, Circassia, Genentech, Novartis, and Teva. A. T. Peters is a consultant at and receives research support from Regeneron Pharmaceuticals, Inc., and Sanofi; receives research support from AstraZeneca; and is a consultant at OptiNose. I. D. Pavord receives speaker fees from Aerocrine AB, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis, and Teva; receives payments for organizing educational events from AstraZeneca and Teva; receives consultant fees from Almirall, AstraZeneca, Boehringer Ingelheim, Circassia, Chiesi, Dey Pharma, Genentech, GSK, Knopp Biosciences, Merck, MSD, Napp Pharmaceuticals, Novartis, Regeneron Pharmaceuticals, Inc., RespiVert, Sanofi, Schering-Plough, and Teva; receives international scientific meeting sponsorship from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Napp Pharmaceuticals, and Teva; and research grant from Chiesi. L. B. Ford receives grant support through institution from 3M, Aimmune, AstraZeneca, DBV, Genentech, GSK, Glenmark, Hoffman-La Roche, Novartis, Pearl, Sanofi, and Teva; and is a national consultant at Sanofi. L. Sher is an advisor at Aimmune, OptiNose, Regeneron Pharmaceuticals, Inc., and Sanofi Genzyme; receives speaker fees from Regeneron Pharmaceuticals, Inc., and Sanofi Genzyme; and has clinical trials in Aimmune, Amgen, AstraZeneca, Circassia, DBV, Galderma, GSK, Lupin, Merck, Mylan, Novartis, Novo Nordisk, OptiNose, Pearl, Pfizer, Pulmagen, Roxane, Sanofi, Spirometrix, Teva, Vectura, and Watson. K. F. Rabe is a consultant at and receives speaker fees from AstraZeneca, Boehringer Ingelheim, Novartis, Sanofi, and Teva. M. S. Rice, P. Rowe, A. Jagerschmidt, A. H. Khan, G. Pirozzi, L. P. Mannent, and A. Teper are employees of and may hold stock and/or stock options in Sanofi. Y. Lu, S. Harel, S. Kamat, N. Amin, M. Ruddy, and N. M. H. Graham are employees and shareholders of Regeneron Pharmaceuticals, Inc.The authors would like to thank Dianne Barry of Sanofi and Nora Crikelair of Regeneron Pharmaceuticals, Inc. This research was sponsored by Sanofi and Regeneron Pharmaceuticals. ClinicalTrials.gov identifier: NCT01854047. Editorial assistance following the authors' guidance, incorporating comments according to the authors' feedback, and providing support with submission was provided by Xiomara V. Thomas, PhD, and Maggie Tarrio Watson, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals.
Funding Information:
The authors would like to thank Dianne Barry of Sanofi and Nora Crikelair of Regeneron Pharmaceuticals, Inc. This research was sponsored by Sanofi and Regeneron Pharmaceuticals . ClinicalTrials.gov identifier: NCT01854047 . Editorial assistance following the authors' guidance, incorporating comments according to the authors' feedback, and providing support with submission was provided by Xiomara V. Thomas, PhD, and Maggie Tarrio Watson, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals .
Publisher Copyright:
© 2019 The Authors
PY - 2020/2
Y1 - 2020/2
N2 - 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.
AB - 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.
KW - Anti-IL-13
KW - Anti-IL-4
KW - Asthma
KW - Chronic rhinosinusitis
KW - Dupilumab
KW - Efficacy
KW - Safety
UR - http://www.scopus.com/inward/record.url?scp=85072342261&partnerID=8YFLogxK
U2 - 10.1016/j.jaip.2019.07.016
DO - 10.1016/j.jaip.2019.07.016
M3 - Article
C2 - 31351189
AN - SCOPUS:85072342261
SN - 2213-2198
VL - 8
SP - 527-539.e9
JO - Journal of Allergy and Clinical Immunology: In Practice
JF - Journal of Allergy and Clinical Immunology: In Practice
IS - 2
ER -