Dupilumab Improves Asthma and Sinonasal Outcomes in Adults with Moderate to Severe Atopic Dermatitis

Mark Boguniewicz; Lisa A Beck; Lawrence Sher; Emma Guttman-Yassky; Diamant Thaçi; Andrew Blauvelt; Margitta Worm; Jonathan Corren; Weily Soong; Peter Lio; Ana B Rossi; Yufang Lu; Jingdong Chao; Laurent Eckert; Abhijit Gadkari; Thomas Hultsch; Marcella Ruddy; Leda P Mannent; Neil M H Graham; Gianluca Pirozzi; Zhen Chen; Marius Ardeleanu

doi:10.1016/j.jaip.2020.12.059

Dupilumab Improves Asthma and Sinonasal Outcomes in Adults with Moderate to Severe Atopic Dermatitis

J Allergy Clin Immunol Pract. 2021 Mar;9(3):1212-1223.e6. doi: 10.1016/j.jaip.2020.12.059. Epub 2021 Jan 13.

Authors

Mark Boguniewicz¹, Lisa A Beck², Lawrence Sher³, Emma Guttman-Yassky⁴, Diamant Thaçi⁵, Andrew Blauvelt⁶, Margitta Worm⁷, Jonathan Corren⁸, Weily Soong⁹, Peter Lio¹⁰, Ana B Rossi¹¹, Yufang Lu¹², Jingdong Chao¹², Laurent Eckert¹³, Abhijit Gadkari¹², Thomas Hultsch¹¹, Marcella Ruddy¹², Leda P Mannent¹³, Neil M H Graham¹², Gianluca Pirozzi¹⁴, Zhen Chen¹², Marius Ardeleanu¹²

Affiliations

¹ National Jewish Health, Denver, Colo; University of Colorado School of Medicine, Denver, Colo. Electronic address: boguniewiczm@njhealth.org.
² Department of Dermatology, University of Rochester Medical Center, Rochester, NY.
³ Peninsula Research Associates, Rolling Hills Estates, Calif.
⁴ Department of Dermatology, Icahn School of Medicine at Mount Sinai Medical Center, New York, NY; Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
⁵ Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany.
⁶ Oregon Medical Research Center, Portland, Ore.
⁷ Division of Allergy and Immunology, Allergy Center Charité, Charité-Universitätsmedizin Berlin, Berlin, Germany.
⁸ David Geffen School of Medicine at UCLA, Los Angeles, Calif.
⁹ Alabama Allergy and Asthma Center, Birmingham, Ala.
¹⁰ Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Ill.
¹¹ Sanofi Genzyme, Cambridge, Mass.
¹² Regeneron Pharmaceuticals, Inc, Tarrytown, NY.
¹³ Sanofi, Chilly-Mazarin, France.
¹⁴ Sanofi, Bridgewater, NJ.

PMID: 33453450
DOI: 10.1016/j.jaip.2020.12.059

Abstract

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.

Trial registration: ClinicalTrials.gov NCT02277743 NCT02755649 NCT02260986 NCT02277769.

Keywords: ACQ-5; Allergic rhinitis; Asthma; Atopic dermatitis; Dupilumab; Eczema; Rhinosinusitis; SNOT-22; Type 2 inflammation; Type 2 inflammatory diseases.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antibodies, Monoclonal, Humanized
Asthma* / drug therapy
Dermatitis, Atopic* / drug therapy
Double-Blind Method
Humans
Severity of Illness Index
Treatment Outcome

Substances

Antibodies, Monoclonal, Humanized
dupilumab

Associated data

ClinicalTrials.gov/NCT02277743
ClinicalTrials.gov/NCT02755649
ClinicalTrials.gov/NCT02260986
ClinicalTrials.gov/NCT02277769