Asthma · Biologics for severe asthma
Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma
| Design | Phase 3, randomised, double-blind, placebo-controlled trial |
|---|---|
| Treatment | Dupilumab 200 mg or 300 mg subcutaneously every 2 weeks |
| Control | Matched placebo |
| Population | 1902 patients aged 12 and over with moderate-to-severe uncontrolled asthma |
| Follow-up | 52 weeks |
| Primary endpoint | Annualised rate of severe asthma exacerbations |
| Result | Severe exacerbations occurred at 0.46 per year (95% CI 0.39 to 0.53) with dupilumab 200 mg versus 0.87 (0.72 to 1.05) with placebo — 47.7% lower (p<0.001), with similar results at 300 mg. FEV1 at week 12 increased by 0.32 L with the lower dose, a difference of 0.14 L versus placebo (p<0.001). Benefit was greater at higher baseline eosinophil counts, and hypereosinophilia occurred in some patients. |
| Secondary endpoints | FEV1, asthma control, benefit by baseline eosinophil count, oral steroid reduction |
In this trial, patients who received dupilumab had significantly lower rates of severe asthma exacerbation than those who received placebo, as well as better lung function and asthma control. Greater benefits were seen in patients with higher baseline levels of eosinophils. Hypereosinophilia was observed in some patients.
The trial authors, in the published abstract
Blocking IL-4 and IL-13 rather than IL-5 gives a larger bronchodilator effect than the anti-IL-5 agents — 0.14 L is substantial for a biologic. The transient hypereosinophilia is a recognised and usually benign quirk of the mechanism, but it needs explaining to patients before it appears on a blood count.
Castro M, Corren J, Pavord ID, et al. Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma. N Engl J Med 2018 Jun 28;378(26):2486-2496.