Clinical Pearls & Morning Reports
Published June 27, 2018
Rabe et al. conducted a phase 3 trial to assess the efficacy and safety of dupilumab, as compared with placebo, in reducing the maintenance dose of oral glucocorticoids in patients with glucocorticoid-dependent severe asthma. The primary efficacy end point was the percentage reduction in the oral glucocorticoid dose from baseline to week 24 while asthma control was maintained. Read the latest Original Article here.
Q: What currently approved biologic agents have shown oral glucocorticoid–sparing effects in patients with severe asthma?
A: The use of the currently approved biologic agents mepolizumab and benralizumab with anti–interleukin-5 mechanisms has shown oral glucocorticoid–sparing effects in patients with severe asthma.
Q: What is dupilumab?
A: Dupilumab is a fully human monoclonal antibody directed against the alpha subunit of the interleukin-4–receptor component that is common to signal transduction for both interleukin-4 and interleukin-13, and dupilumab treatment has the capacity to reduce type 2 inflammation. Patients with glucocorticoid-dependent asthma may present with type 2 inflammatory disease, as shown by elevated levels in the fraction of exhaled nitric oxide (FeNO), IgE, and other type 2 inflammation biomarkers.
A: The trial by Rabe et al. showed that dupilumab as an add-on therapy significantly reduced oral glucocorticoid use in patients with oral glucocorticoid–dependent severe asthma. The percentage change in the glucocorticoid dose was −70.1% in the dupilumab group, as compared with −41.9% in the placebo group (P<0.001); 80% versus 50% of the patients had a dose reduction of at least 50%, 69% versus 33% had a dose reduction to less than 5 mg per day, and 48% versus 25% completely discontinued oral glucocorticoid use. In the overall population, dupilumab treatment resulted in a rate of severe asthma exacerbations that was 59% lower than that in the placebo group and in an FEV1 that was 0.22 liters higher. Although there was a change in the magnitude of the outcome according to the blood eosinophil count, dupilumab treatment was associated with a greater reduction in the dose of oral glucocorticoid than was placebo, regardless of the baseline blood eosinophil count. The magnitude of the effect was largest in patients with a higher eosinophil count at baseline.
A: Dupilumab treatment was associated with transient eosinophilia, which was observed in 14% of the patients in the dupilumab group. Patients in the dupilumab group had a greater mean transient increase from baseline in blood eosinophil counts than those in the placebo group, with a higher percentage of patients (13%) having an eosinophil count of more than 3000 cells per cubic millimeter. The high blood eosinophil counts returned to baseline levels by the end of the dupilumab treatment period. Patients with transient elevations in the blood eosinophil counts did not have concomitant clinical adverse events or consequences. No adverse events of conjunctivitis during the 24-week intervention period were observed in either group, in contrast to findings in studies of dupilumab in patients with atopic dermatitis.