Efficacy of dupilumab on clinical outcomes in patients with asthma and perennial allergic rhinitis

Ann Allergy Asthma Immunol. 2020 Nov;125(5):565-576.e1. doi: 10.1016/j.anai.2020.05.026. Epub 2020 May 28.

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 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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Allergic Agents / therapeutic use*
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Asthma / drug therapy*
  • Biomarkers
  • Double-Blind Method
  • Eosinophils / cytology
  • Female
  • Forced Expiratory Volume / drug effects
  • Humans
  • Immunoglobulin E / blood
  • Male
  • Middle Aged
  • Quality of Life
  • Receptors, Interleukin-4, Type II / antagonists & inhibitors
  • Rhinitis, Allergic, Perennial / drug therapy*

Substances

  • Anti-Allergic Agents
  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • Receptors, Interleukin-4, Type II
  • Immunoglobulin E
  • dupilumab