Antibody Therapy for Eczema May Cut Severe Asthma Exacerbations in Half | NEJM

 

Publication 

  • New England Journal of Medicine
  • Castro & Tohda et al, May 2018

Key Points

  • Dupilumab: monoclonal antibody targets IL-4 receptor (blocks  IL-4, IL-13 response)
  • Biweekly subcutaneous injection
  • 47.7% decrease in severe asthma exacerbations w/ dupilumab vs. placebo
  • Best response (66% fewer exacerbations) if blood eosinophils > 300/mm³
  •  + 0.14 L ΔFEV1 relative to placebo (after 12 weeks)
  • Rate of adverse rxns similar in tx and ctl groups (most common: injection site reaction)

Background

  • 20% asthma cases poorly controlled
  • ~4,000 deaths attributed to asthma in US annually
  • Type II inflammation (mediated by IL-4, IL-5, IL-13 response) involved in 50% of asthma patients
  • Anti-IL-5 antibodies may also be effective as adjunct in severe asthma
  • Eosinophilia, serum IgE biomarkers for type II inflammation/asthma severity
  • Dupilumab approved in 2017 for atopic dermatitis
  • $1,460/injection

Methodology

  • LIBERTY ASTHMA QUEST trial, 1902 patients >12y w/ uncontrolled asthma
  • Randomized placebo-controlled trial, double-blind, phase III
  • Subq Q2w 200 mg dupilumab (loading dose, 400 mg) or 300 mg (loading dose, 600 mg) or a matched-volume placebo, added onto patients’ existing therapies (e.g., inhaled corticosteroids +/- bronchodilators)
  • Primary endpoints: # asthma exacerbations, ΔFEV1 after 12w in all patients
  • Secondary end points: # asthma exacerbations, and FEV1 in patient subset w/ blood eosinophils >300/mm³
  • Funded by Sanofi, Regeneron

 

Source: Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma | NEJM

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