Dupilumab modestly reduces asthma exacerbations at a high price

Référence

Castro M, Corren J, Maspero J, et al. Dupilumab efficacy and safety in moderate to severe uncontrolled asthma. N Engl J Med 2018;378(26):2486-2496.

Sommaire

Dupilumab is a monoclonal antibody that blocks the interleukin 4 and interleukin 13 receptors in the inflammatory pathway.The authors identified 1902 patients, 12 years and older, with uncontrolled asthma (defined as currently taking a medium to high dose of an inhaled corticosteroid and up to 2 other controller medications, and having an FEV1 of 80% or less than predicted, evidence of reversability with bronchodilators, a score of at least 1.5 on the Asthma Control Questionnaire, and at least one severe asthma exacerbation in the past year [defined as requiring an emergency department visit, hospitalization, or at least 3 days of systemic corticosteroids]). These patients were randomized in a 2:2:1:1 ratio to 1 of 4 groups: subcutaneous dupilumab 200 mg every 2 weeks, subcutaneous dupilumab 300 mg every 2 weeks, or placebo in volumes to match the active drug delivery. Groups were similar at baseline, with a mean age of 48 years, 63% women, and a baseline FEV1 of 58% of predicted. The primary outcome—the likelihood of a severe asthma exacerbation—was significantly less likely in the dupilumab groups. For the 200-mg dose, the annualized rates of a severe asthma exacerbation were 0.46 in the active treatment group and 0.87 in the placebo group (P < .001), with a similar benefit in the higher-dose group. Having 0.4 fewer severe exacerbations per year would amount to approximately 1 fewer severe exacerbation over 2.5 years. The benefit was greatest among patients with baseline eosinphilia greater than 300 cells/mm3, and in those with a fractional excretion of inhaled nitric oxide (FeNO) of greater than 25 ppb. In fact, patients with less than 150 eosinophils/mm3 or an FeNO of less than 25 ppb did not benefit at all. Digging into the supplemental appendix, it appears from Table S6 that the majority of the severe exacerbations were classified that way because the patient received an outpatient dose of at least 3 days of oral steroids, with a reduction from only 0.065 to 0.035 hospitalizations or emergency department visits per year (ie, a reduction of 0.03 events). This was an industry-sponsored study.