William W Busse1, Jorge F Maspero2, Yufang Lu3, Jonathan Corren4, Nicola A Hanania5, Bradley E Chipps6, Constance H Katelaris7, J Mark FitzGerald8, Santiago Quirce9, Linda B Ford10, Megan S Rice11, Siddhesh Kamat3, Asif H Khan12, Alexandre Jagerschmidt12, Sivan Harel3, Paul Rowe13, Gianluca Pirozzi13, Nikhil Amin3, Marcella Ruddy3, Neil M H Graham3, Ariel Teper13. 1. 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. 2. Fundación CIDEA, Buenos Aires, Argentina. 3. Regeneron Pharmaceuticals, Inc, Tarrytown, New York. 4. David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California. 5. Baylor College of Medicine, Texas Medical Center, Houston, Texas. 6. Capital Allergy and Respiratory Disease Center, Sacramento, California. 7. Campbelltown Hospital and Western Sydney University, Campbelltown, Australia. 8. The University of British Columbia, Vancouver, British Columbia. 9. Department of Allergy, Hospital La Paz Institute for Health Research (IdiPAZ), Madrid, Spain. 10. Asthma and Allergy Center, Bellevue, Nebraska. 11. Sanofi, Cambridge, Massachusetts. 12. Sanofi, Chilly-Mazarin, France. 13. Sanofi, Bridgewater, New Jersey.
Abstract
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 (FEV1) 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 dupilumabefficacy in LIBERTY ASTHMA QUEST patients with comorbid PAR. METHODS:Severe asthma exacerbation rates, FEV1, 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 FEV1 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/μL) 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.
RCT Entities:
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 (FEV1) 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, FEV1, 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 FEV1 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/μL) 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.
Authors: Andrew Gallagher; Michaela Edwards; Parameswaran Nair; Stewart Drew; Aashish Vyas; Rashmi Sharma; Paul A Marsden; Ran Wang; David Jw Evans Journal: Cochrane Database Syst Rev Date: 2021-10-19
Authors: Jonathan Corren; Sarbjit S Saini; Remi Gagnon; Mark H Moss; Gordon Sussman; Joshua Jacobs; Elizabeth Laws; Elinore S Chung; Tatiana Constant; Yiping Sun; Jennifer Maloney; Jennifer D Hamilton; Marcella Ruddy; Claire Q Wang; Meagan P O'Brien Journal: J Asthma Allergy Date: 2021-08-16
Authors: Mohamed A Kamal; Yoko Franchetti; Ching-Ha Lai; Christine Xu; Claire Q Wang; Allen R Radin; Meagan P O'Brien; Marcella Ruddy; John D Davis Journal: J Clin Pharmacol Date: 2022-01-06 Impact factor: 2.860