TY - JOUR
T1 - Dupilumab Improves Asthma and Sinonasal Outcomes in Adults with Moderate to Severe Atopic Dermatitis
AU - Boguniewicz, Mark
AU - Beck, Lisa A.
AU - Sher, Lawrence
AU - Guttman-Yassky, Emma
AU - Thaçi, Diamant
AU - Blauvelt, Andrew
AU - Worm, Margitta
AU - Corren, Jonathan
AU - Soong, Weily
AU - Lio, Peter
AU - Rossi, Ana B.
AU - Lu, Yufang
AU - Chao, Jingdong
AU - Eckert, Laurent
AU - Gadkari, Abhijit
AU - Hultsch, Thomas
AU - Ruddy, Marcella
AU - Mannent, Leda P.
AU - Graham, Neil M.H.
AU - Pirozzi, Gianluca
AU - Chen, Zhen
AU - Ardeleanu, Marius
N1 - Funding Information:
Conflicts of interest: M. Boguniewicz has received grants as an investigator from Regeneron Pharmaceuticals, Inc; and has received honoraria as a consultant from Regeneron Pharmaceuticals, Inc and Sanofi Genzyme. L. A. Beck has received honoraria as a consultant from AbbVie, Allakos, Arena Pharma, AstraZeneca, Connect Biopharma, Eli Lilly, LEO Pharma, Novan, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc, Sanofi, UCB, and Vimalan; has received grants for clinical trials from AbbVie, LEO Pharma, Pfizer, and Regeneron Pharmaceuticals, Inc; and holds stock in Pfizer and Medtronic. L. Sher has received study grants from Regeneron Pharmaceuticals, Inc; has received grants from Glenmark, Pfizer, and Sanofi Genzyme; and is on the advisory board of Regeneron Pharmaceuticals, Inc and Sanofi Genzyme. E. Guttman-Yassky has received personal fees from AbbVie, Allergan, Amgen, Asana BioSciences, Celgene, Concert, Dermavant, Dermira, DS Biopharma, Eli Lilly, Escalier BioSciences, Galderma, Glenmark, Kyowa Kirin, LEO Pharma, Mitsubishi Tanabe, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc, and Sanofi; and has received grants paid to the institution from AbbVie, Asana Biosciences, Celgene, Concert, Dermavant, Dermira, DS Biopharma, Galderma, Glenmark, Innovaderm, LEO Pharma, Novan, Novartis, Pfizer, Ralexar Therapeutics, and Regeneron Pharmaceuticals, Inc. D. Thaçi has received research support and grants for clinical trials paid to the institution from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Celgene, DS Pharma, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, LEO Pharma, MSD, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc, Sandoz, and Sanofi; and has received honoraria as a consultant and is a member of advisory board or lectures at AbbVie, Almirall, Celgene, DS Pharma, Galapagos, Galderma, Janssen, JTE, LEO Pharma, Medac, MorphoSys, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc, Samsung, Sanofi, and UCB. A. Blauvelt is a scientific advisor and clinical study investigator for AbbVie, Aclaris, Almirall, Arena Pharmaceuticals, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Dermira, Eli Lilly, FLX Bio, Forte, Galderma, Janssen, LEO Pharma, Novartis, Ortho, Pfizer, Regeneron Pharmaceuticals, Inc, Sandoz, Sanofi Genzyme, Sun Pharma, and UCB; and is a paid speaker for AbbVie. M. Worm is Principal Investigator in clinical trials (including SOLO 1 and SOLO 2, SOLO CONTINUE, and CHRONOS) and has received honoraria for consulting and lecture activity from Regeneron Pharmaceuticals, In., and Sanofi; and has received honoraria for lectures and/or advisory board activity from ALK-Abelló, Allergopharma GmbH, Allergy Therapeutics, HAL Allergy, KG Pharma, LEO Pharma, Meda Pharma, Novartis, and Sanofi. J. Corren has received research funding from Sanofi. W. Soong has received research funding from AbbVie, AstraZeneca, Cara, Galderma, Genentech, GlaxoSmithKline, Glenmark, Innovaderm, LEO Pharma, Mandala, Menlo, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc, Relaxar, Sanofi, Symbio, Teva, and Vanda Pharmaceuticals; and has received speaker fees from AstraZeneca, GlaxoSmithKline, Optinose, Regeneron Pharmaceuticals, Inc, and Sanofi; and has received consulting fees from AbbVie, Genentech, Regeneron Pharmaceuticals, Inc., and Teva. P. Lio has received grants paid to institution/practice for research and is on advisory boards and speakers' bureaus of Regeneron Pharmaceuticals, Inc and Sanofi Genzyme. A. B. Rossi is an employee of Sanofi Genzyme and may hold stock and/or stock options in the company. Y. Lu, J. Chao, A. Gadkari, M. Ruddy, N.M.H. Graham, Z. Chen, and M. Ardeleanu are employees and shareholders of Regeneron Pharmaceuticals, Inc. L. Eckert, T. Hultsch, L. P. Mannent, and G. Pirozzi are employees of Sanofi and may hold stock and/or stock options in the company.This research was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Medical writing and editorial assistance were funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. The authors thank the patients and their families for their participation in the studies, their colleagues for their support; Qiuyue Chen and Linda Williams (Regeneron Pharmaceuticals, Inc); and El-Bdaoui Haddad (Sanofi Genzyme); and Heribert Staudinger (Sanofi) for their contributions. Medical writing and editorial assistance were provided by Lola MacRae, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. ClinicalTrials.gov Identifiers: NCT02277743 (SOLO 1), NCT02277769 (SOLO 2), NCT02260986 (CHRONOS), and NCT02755649 (CAFÉ).
Funding Information:
This research was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc . Medical writing and editorial assistance were funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc . The authors thank the patients and their families for their participation in the studies, their colleagues for their support; Qiuyue Chen and Linda Williams ( Regeneron Pharmaceuticals , Inc); and El-Bdaoui Haddad ( Sanofi Genzyme ); and Heribert Staudinger ( Sanofi ) for their contributions. Medical writing and editorial assistance were provided by Lola MacRae, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. ClinicalTrials.gov Identifiers: NCT02277743 (SOLO 1), NCT02277769 (SOLO 2), NCT02260986 (CHRONOS), and NCT02755649 (CAFÉ).
Publisher Copyright:
© 2021 The Authors
PY - 2021/3
Y1 - 2021/3
N2 - Background: Dupilumab has demonstrated efficacy with acceptable safety in clinical trials in patients with moderate to severe atopic dermatitis (AD). Objective: To assess dupilumab's impact on asthma and sinonasal conditions in adult patients with moderate to severe AD in four randomized, double-blinded, placebo-controlled trials. Methods: In LIBERTY AD SOLO 1 (NCT02277743), SOLO 2 (NCT02755649), CHRONOS (NCT02260986), and CAFÉ (NCT02755649), patients received placebo, dupilumab 300 mg every 2 weeks (q2w), or dupilumab 300 mg weekly (qw). In CHRONOS and CAFÉ, patients received concomitant topical corticosteroids. This post hoc analysis assessed Asthma Control Questionnaire-5 (ACQ-5) scores in patients with asthma, Sino-Nasal Outcome Test-22 (SNOT-22) scores in patients with sinonasal conditions, and AD signs and symptoms in all patients. Results: Of the 2444 patients, 463 had asthma with baseline ACQ-5 ≥ 0.5 (19%); 1171 had sinonasal conditions (48%); and 311 had both (13%). At week 16, ACQ-5 scores (least squares mean change from baseline [standard error]) improved by 0.27 (0.07), 0.59 (0.08), and 0.56 (0.07) in placebo-, q2w-, and qw-treated patients with asthma, respectively, whereas SNOT-22 scores improved by 5.1 (0.8), 9.9 (0.9), and 10.8 (0.8) in patients with sinonasal conditions (P < .01 for all dupilumab vs placebo). Improvements in ACQ-5 and SNOT-22 were also seen in patients with both conditions. Dupilumab also significantly improved AD signs and symptoms among all subgroups. Conclusions: In this first analysis of patients with comorbid moderate to severe AD, asthma, and/or chronic sinonasal conditions, dupilumab improved all three diseases in a clinically meaningful and statistically significant manner (vs placebo), based on validated outcome measures.
AB - Background: Dupilumab has demonstrated efficacy with acceptable safety in clinical trials in patients with moderate to severe atopic dermatitis (AD). Objective: To assess dupilumab's impact on asthma and sinonasal conditions in adult patients with moderate to severe AD in four randomized, double-blinded, placebo-controlled trials. Methods: In LIBERTY AD SOLO 1 (NCT02277743), SOLO 2 (NCT02755649), CHRONOS (NCT02260986), and CAFÉ (NCT02755649), patients received placebo, dupilumab 300 mg every 2 weeks (q2w), or dupilumab 300 mg weekly (qw). In CHRONOS and CAFÉ, patients received concomitant topical corticosteroids. This post hoc analysis assessed Asthma Control Questionnaire-5 (ACQ-5) scores in patients with asthma, Sino-Nasal Outcome Test-22 (SNOT-22) scores in patients with sinonasal conditions, and AD signs and symptoms in all patients. Results: Of the 2444 patients, 463 had asthma with baseline ACQ-5 ≥ 0.5 (19%); 1171 had sinonasal conditions (48%); and 311 had both (13%). At week 16, ACQ-5 scores (least squares mean change from baseline [standard error]) improved by 0.27 (0.07), 0.59 (0.08), and 0.56 (0.07) in placebo-, q2w-, and qw-treated patients with asthma, respectively, whereas SNOT-22 scores improved by 5.1 (0.8), 9.9 (0.9), and 10.8 (0.8) in patients with sinonasal conditions (P < .01 for all dupilumab vs placebo). Improvements in ACQ-5 and SNOT-22 were also seen in patients with both conditions. Dupilumab also significantly improved AD signs and symptoms among all subgroups. Conclusions: In this first analysis of patients with comorbid moderate to severe AD, asthma, and/or chronic sinonasal conditions, dupilumab improved all three diseases in a clinically meaningful and statistically significant manner (vs placebo), based on validated outcome measures.
KW - ACQ-5
KW - Allergic rhinitis
KW - Asthma
KW - Atopic dermatitis
KW - Dupilumab
KW - Eczema
KW - Rhinosinusitis
KW - SNOT-22
KW - Type 2 inflammation
KW - Type 2 inflammatory diseases
UR - http://www.scopus.com/inward/record.url?scp=85100551147&partnerID=8YFLogxK
U2 - 10.1016/j.jaip.2020.12.059
DO - 10.1016/j.jaip.2020.12.059
M3 - Article
C2 - 33453450
AN - SCOPUS:85100551147
SN - 2213-2198
VL - 9
SP - 1212-1223.e6
JO - Journal of Allergy and Clinical Immunology: In Practice
JF - Journal of Allergy and Clinical Immunology: In Practice
IS - 3
ER -