PMID- 32474156 OWN - NLM STAT- MEDLINE DCOM- 20201204 LR - 20201214 IS - 1534-4436 (Electronic) IS - 1081-1206 (Linking) VI - 125 IP - 5 DP - 2020 Nov TI - Efficacy of dupilumab on clinical outcomes in patients with asthma and perennial allergic rhinitis. PG - 565-576.e1 LID - S1081-1206(20)30389-6 [pii] LID - 10.1016/j.anai.2020.05.026 [doi] AB - BACKGROUND: Comorbid perennial allergic rhinitis (PAR) or year-round aeroallergen sensitivity substantially contributes to disease burden in patients with asthma. Dupilumab blocks the shared receptor for interleukin (IL) 4 and IL-13, key drivers of type 2 inflammation that play important roles in asthma and PAR. In the LIBERTY ASTHMA QUEST trial (NCT02414854), dupilumab reduced severe asthma exacerbations and improved forced expiratory volume in 1 second (FEV(1)) in patients with uncontrolled, moderate-to-severe asthma, with greater efficacy observed in patients with elevated type 2 inflammatory biomarkers at baseline (blood eosinophils and fractional exhaled nitric oxide). OBJECTIVE: To assess dupilumab efficacy in LIBERTY ASTHMA QUEST patients with comorbid PAR. METHODS: Severe asthma exacerbation rates, FEV(1), asthma control (5-item Asthma Control Questionnaire), rhinoconjunctivitis-specific health-related quality of life (Standardized Rhinoconjunctivitis Quality of Life Questionnaire +12 scores), and type 2 inflammatory biomarkers during the 52-week treatment period were assessed. RESULTS: A total of 814 of the 1902 patients (42.8%) had comorbid PAR (defined as an allergic rhinitis history and >/=1 perennial aeroallergen specific immunoglobulin E (IgE) level >/=0.35 kU/L at baseline). Dupilumab, 200 and 300 mg every 2 weeks, vs placebo reduced severe exacerbations rates by 32.2% and 34.6% (P < .05 for both) and improved FEV(1) at week 12 by 0.14 L and 0.18 L (P < .01 for both); greater efficacy was observed in patients with elevated baseline blood eosinophil counts (>/=300 cells/muL) and fractional exhaled nitric oxide. Dupilumab treatment also numerically improved the 5-item Asthma Control Questionnaire and Standardized Rhinoconjunctivitis Quality of Life Questionnaire +12 scores and suppressed type 2 inflammatory biomarkers. CONCLUSION: Dupilumab improved key asthma-related outcomes, asthma control, and rhinoconjunctivitis-specific health-related quality of life while suppressing type 2 inflammatory biomarkers and perennial allergen-specific IgE in patients with moderate-to-severe asthma and comorbid PAR, highlighting its dual inhibitory effects on IL-4 and IL-13 and its role in managing asthma and PAR. CI - Copyright (c) 2020 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Busse, William W AU - Busse WW AD - Division of Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. Electronic address: wwb@medicine.wisc.edu. FAU - Maspero, Jorge F AU - Maspero JF AD - Fundacion CIDEA, Buenos Aires, Argentina. FAU - Lu, Yufang AU - Lu Y AD - Regeneron Pharmaceuticals, Inc, Tarrytown, New York. FAU - Corren, Jonathan AU - Corren J AD - David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California. FAU - Hanania, Nicola A AU - Hanania NA AD - Baylor College of Medicine, Texas Medical Center, Houston, Texas. FAU - Chipps, Bradley E AU - Chipps BE AD - Capital Allergy and Respiratory Disease Center, Sacramento, California. FAU - Katelaris, Constance H AU - Katelaris CH AD - Campbelltown Hospital and Western Sydney University, Campbelltown, Australia. FAU - FitzGerald, J Mark AU - FitzGerald JM AD - The University of British Columbia, Vancouver, British Columbia. FAU - Quirce, Santiago AU - Quirce S AD - Department of Allergy, Hospital La Paz Institute for Health Research (IdiPAZ), Madrid, Spain. FAU - Ford, Linda B AU - Ford LB AD - Asthma and Allergy Center, Bellevue, Nebraska. FAU - Rice, Megan S AU - Rice MS AD - Sanofi, Cambridge, Massachusetts. FAU - Kamat, Siddhesh AU - Kamat S AD - Regeneron Pharmaceuticals, Inc, Tarrytown, New York. FAU - Khan, Asif H AU - Khan AH AD - Sanofi, Chilly-Mazarin, France. FAU - Jagerschmidt, Alexandre AU - Jagerschmidt A AD - Sanofi, Chilly-Mazarin, France. FAU - Harel, Sivan AU - Harel S AD - Regeneron Pharmaceuticals, Inc, Tarrytown, New York. FAU - Rowe, Paul AU - Rowe P AD - Sanofi, Bridgewater, New Jersey. FAU - Pirozzi, Gianluca AU - Pirozzi G AD - Sanofi, Bridgewater, New Jersey. FAU - Amin, Nikhil AU - Amin N AD - Regeneron Pharmaceuticals, Inc, Tarrytown, New York. FAU - Ruddy, Marcella AU - Ruddy M AD - Regeneron Pharmaceuticals, Inc, Tarrytown, New York. FAU - Graham, Neil M H AU - Graham NMH AD - Regeneron Pharmaceuticals, Inc, Tarrytown, New York. FAU - Teper, Ariel AU - Teper A AD - Sanofi, Bridgewater, New Jersey. LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20200528 PL - United States TA - Ann Allergy Asthma Immunol JT - Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology JID - 9503580 RN - 0 (Anti-Allergic Agents) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Biomarkers) RN - 0 (Receptors, Interleukin-4, Type II) RN - 37341-29-0 (Immunoglobulin E) RN - 420K487FSG (dupilumab) SB - IM MH - Adult MH - Anti-Allergic Agents/*therapeutic use MH - Antibodies, Monoclonal, Humanized/*therapeutic use MH - Asthma/*drug therapy MH - Biomarkers MH - Double-Blind Method MH - Eosinophils/cytology MH - Female MH - Forced Expiratory Volume/drug effects MH - Humans MH - Immunoglobulin E/blood MH - Male MH - Middle Aged MH - Quality of Life MH - Receptors, Interleukin-4, Type II/antagonists & inhibitors MH - Rhinitis, Allergic, Perennial/*drug therapy EDAT- 2020/06/01 06:00 MHDA- 2020/12/15 06:00 CRDT- 2020/06/01 06:00 PHST- 2020/04/23 00:00 [received] PHST- 2020/05/21 00:00 [accepted] PHST- 2020/06/01 06:00 [pubmed] PHST- 2020/12/15 06:00 [medline] PHST- 2020/06/01 06:00 [entrez] AID - S1081-1206(20)30389-6 [pii] AID - 10.1016/j.anai.2020.05.026 [doi] PST - ppublish SO - Ann Allergy Asthma Immunol. 2020 Nov;125(5):565-576.e1. doi: 10.1016/j.anai.2020.05.026. Epub 2020 May 28.