Dupilumab Efficacy in Patients With Uncontrolled, Moderate-to-Severe Allergic Asthma

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AAP Policy SupplementsSupplements Publish Supplement MultimediaVideo Abstracts Pediatrics On Call Podcast Subscribe Alerts Careers We will not be accepting article comments until November 8, 2021, while our site undergoes major changes. We apologize for the inconvenience. For questions, contact the editorial office. Asthma Dupilumab Efficacy in Patients With Uncontrolled, Moderate-to-Severe Allergic Asthma Mechelle A. Miller and Karla L. Davis Pediatrics December 2020, 146 (Supplement 4) S375; DOI: https://doi.org/10.1542/peds.2020-023861IIII Mechelle A. Miller Honolulu, HawaiiFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteKarla L. Davis Honolulu, HawaiiFind this author on Google ScholarFind this author on PubMedSearch for this author on this site ArticleInfo & MetricsComments Download PDF J Corren, M Castro, T O’Riordan. J Allergy Clin Immunol Pract. 2020;8(2):516–526PURPOSE OF THE STUDY:IL-4 and IL-13 are drivers of type 2 inflammation, including IgE-mediated allergic inflammation in asthma. Dupilumab blocks the shared receptor component for IL-4 and IL-13, inhibiting subsequent signaling of cytokines which drive type 2 inflammation. This study evaluated the effect of dupilumab on asthma outcome measures in subgroups of patients with asthma.STUDY POPULATION:This study is a post hoc analysis of patients enrolled in a phase 3, randomized, double-blind, placebo-controlled study of efficacy and safety of dupilumab, which enrolled adolescents and adults ≥12 years with physician-diagnosed asthma receiving treatment with a medium-to-high dose inhaled glucocorticoid and up to 2 additional controllers. Allergic asthma criteria included total serum IgE ≥30 IU/mL and ≥1 positive perennial aeroallergen-specific IgE ≥0.35 kU/L. A total of 1902 patients were randomized in a 2:2:1:1 ratio to add-on subcutaneous dupilumab 200 mg (loading dose 400 mg) or 300 mg (loading dose 600 mg) every 2 weeks or matched-volume placebos for 52 weeks. One thousand eighty-three patients met the criteria used to define allergic asthma, whereas 819 patients did not meet these criteria.METHODS:Efficacy analyses were performed in the intention-to-treat population of all randomized patients. Evaluated endpoints were annualized severe exacerbation rates, change from baseline in prebronchodilator forced expiratory volume in one second (FEV1), and change from baseline in 5-item Asthma Control Questionnaire (ACQ-5) score over the treatment period. Dupilumab effects on type 2 inflammation biomarkers including serum total IgE, fractional exhaled nitric oxide (FeNO), and serum thymus and activation-regulated chemokine (TARC) were also assessed in both subgroups.RESULTS:In the allergic asthma subgroup, dupilumab 200/300 mg every 2 weeks versus placebo reduced severe asthma exacerbation rates (−36.9%/−45.5%), and improved FEV1 by least-squares mean at week 12 (0.13 L/0.16 L). In the nonallergic asthma subgroup, dupilumab 200/300 mg reduced severe asthma exacerbation rates (−60.0%/−44.6%) and improved FEV1 by least-squares mean at week 12 (0.14 L/0.09 L). Dupilumab reduced FeNO after 2 weeks of treatment and reduced TARC concentrations versus placebo at 12 weeks in both subgroups. Reductions were sustained throughout the treatment period. Patients with baseline serum total IgE ≥700 IU/mL also benefitted.CONCLUSIONS:Dupilumab reduced severe exacerbations rates, improved FEV1, improved ACQ-5 scores, and suppressed type 2 inflammatory biomarkers in both subgroups. Severe exacerbation reduction rates and FEV1 improvements were greater in patients with higher baseline levels of type 2 inflammatory biomarkers.REVIEWER COMMENTS:Although further study is needed in patients <12 years, dupilumab demonstrated efficacy in patients with and without increased expression of specific IgE to aeroallergens, suggesting a common role of IL-4 and IL-13 in airway inflammation in both asthma phenotypes studied. Clinical efficacy in patients with baseline serum total IgE ≥700 IU/mL is encouraging and may offer a viable option for patients who are not candidates for omalizumab.Copyright © 2020 by the American Academy of Pediatrics PreviousNext Back to top Advertising Disclaimer » In this issue Pediatrics Vol. 146, Issue Supplement 4 1 Dec 2020 Table of ContentsIndex by author View this article with LENS PreviousNext Email Article Thank you for your interest in spreading the word on American Academy of Pediatrics.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. 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Davis Pediatrics Dec 2020, 146 (Supplement 4) S375; DOI: 10.1542/peds.2020-023861IIII Citation Manager Formats BibTeXBookendsEasyBibEndNote (tagged)EndNote 8 (xml)MedlarsMendeleyPapersRefWorks TaggedRef ManagerRISZotero Share Dupilumab Efficacy in Patients With Uncontrolled, Moderate-to-Severe Allergic Asthma Mechelle A. Miller, Karla L. Davis Pediatrics Dec 2020, 146 (Supplement 4) S375; DOI: 10.1542/peds.2020-023861IIII Share This Article: Copy Print Download PDF Insight Alerts Table of Contents Jump to section ArticlePURPOSE OF THE STUDY:STUDY POPULATION:METHODS:RESULTS:CONCLUSIONS:REVIEWER COMMENTS:Info & MetricsComments Related ArticlesNo related articles found.Google Scholar Cited By...No citing articles found.Google Scholar More in this TOC SectionAsthma Prevalence of Continuous Pulse Oximetry Monitoring in Hospitalized Children With Bronchiolitis Not Requiring Supplemental Oxygen Lung Computational Models and the Role of the Small Airways in Asthma Increased Capsaicin Sensitivity in Patients With Severe Asthma Is Associated With Worse Clinical Outcome Show more Asthma Medical Therapies Tiotropium is Efficacious in 6 to 17 Year-Olds With Asthma, Independent of T2 Phenotype Prescribing Emergency Oral Steroids in Asthma Clinics [published online ahead of print June 11, 2019] Show more Medical Therapies Similar Articles Journal Info Editorial Board Editorial Policies Overview Licensing Information Authors/Reviewers Author Guidelines Submit My Manuscript Open Access Reviewer Guidelines Librarians Institutional Subscriptions Usage Stats Support Contact Us Subscribe Resources Media Kit About International Access Terms of Use Privacy Statement FAQ AAP.org shopAAP Follow American Academy of Pediatrics on Instagram Visit American Academy of Pediatrics on Facebook Follow American Academy of Pediatrics on Twitter Follow American Academy of Pediatrics on Youtube RSS © 2021 American Academy of Pediatrics