Dupilumab Reduces Asthma Exacerbation Rates

Ian Pavord, FRCP, FMedSci

Recent study findings demonstrate the efficacy of dupilumab in significantly reducing severe exacerbation rates in patients with uncontrolled, persistent eosinophilic asthma.

Ian Pavord, FRCP, FMedSci, and colleagues conducted meta-analyses of dupilumab compared with standard of care on annualized severe exacerbation rates in patients with eosinophilic asthma. Dupilumab, a monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4 and IL-13, drivers of type 2 inflammation in multiple diseases.

The investigators obtained data from the phase 3 QUEST and phase 2b studies to identify 3 subgroups of patients with baseline blood eosinophil count, inhaled corticosteroids dose, and number of severe exacerbations that matched the key inclusion criteria of clinical trials of anti-IL-5 biologics. The subgroups of patients had baseline characteristics similar to those of clinical trials for benralizumab (medium-/high-dose inhaled corticosteroid/long-acting β2 -agonist [LABA], eosinophils ≥300 cells/µL, ≥2 previous exacerbations, age at least 12 years old); mepolizumab (high-dose inhaled corticosteroid/LABA, eosinophils ≥150 cells/µL, ≥2 previous exacerbations, age at 12 years old); and reslizumab (medium-/high-dose inhaled corticosteroid/LABA, eosinophils ≥400 cells/µL, ≥1 previous exacerbation, age at least 18 years old).

Pavord and the team pooled the estimates of effect for dupilumab versus standard of care on annualized severe asthma exacerbation rates from the phase 3 and phase 2b studies. They calculated Number Needed to Treat to have 1 less severe exacerbation per year when using dupilumab instead of standard of care.

The team found dupilumab 200 mg and 300 mg every 2 weeks significantly reduced the annualized severe exacerbation rate in all 3 subgroups versus the standard of care. The exacerbation rate ratio for each subgroup was .26 (95% CI, .21-.33), .36 (95% CI, .29-.44), and .29 (95% CI, .23-.36), respectively, which represented a 64-74% relative exacerbation rate reduction.

The Number Needed to Treat was .91 (95% CI, .853-1.005), 1.033 (95% CI, .931-1.18), and 1.107 (95% CI, 1.034-1.228), respectively. These results indicated only 1 patient would need to be treated with dupilumab instead of standard of care to have 1 less severe asthma exacerbation per year.

Overall, the meta-analyses demonstrated dupilumab significantly reduced severe exacerbation rates in subgroups of patients with uncontrolled, persistent eosinophilic asthma.

Dupilumab was approved by the US Food and Drug Administration in 2018 as an add-on maintenance therapy for adults and adolescents at least 12 years old with an eosinophilic phenotype or with oral corticosteroid-dependent asthma.

The study, “Meta-Analyses of Dupilumab Versus Standard of Care in Patients with Uncontrolled, Persistent Asthma,” was presented as part of the American Thoracic Society annual meeting.