Researchers conducted a multinational, double-blind, placebo-controlled pivotal phase 2b dose-ranging study to assess the efficacy and safety of dupilumab as add-on therapy in patients with uncontrolled persistent asthma. They randomized 769 patients to 24 weeks add-on therapy with dupilumab 200 or 300 mg every 2 or 4 weeks (n=611), or to placebo (n=158). Patients with atopy were defined as those with ≥2 positive aeroallergen-specific IgE antibodies at baseline. [EAACI 2016, abstract 609]

For patients with or without atopy, researchers estimated least-square mean change from baseline in lung function at week 12 and adjusted annualized rate of severe exacerbations in the 24-week treatment period. Safety was evaluated based on adverse event reports and laboratory assessments.

At week 12, lung function was significantly improved in patients with or without atopy (p<0.05 for both doses vs placebo). The severe exacerbation rate was reduced in patients with atopy for both doses versus placebo (−59.1 to −77.5 percent; p<0.05). In patients without atopy, improvements similar (or better) to those in patients with atopy were seen for both doses versus placebo (−59.5 to −91.6 percent), but reached statistical significance for the 200 mg dose only (p=0.0029).

The overall incidence of adverse events was similar across treatment groups (dupilumab, 78 to 80 percent; placebo, 75 percent). The most common adverse events in dupilumab-treated patients compared with placebo were upper respiratory tract infection (13 to 15 vs 18 percent) and injection-site erythema (14 to 22 vs 8 percent).

Dupilumab is a fully human anti-interleukin-4 receptor α monoclonal antibody that inhibits interleukin-4 and interleukin-13 signalling, which are key drivers of type-2-mediated inflammation. Adults with uncontrolled persistent asthma who are receiving medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist require additional treatment options as add-on therapy. [Lancet2016;doi:10.1016/S0140-6736(16)30307-5]

A previous trial showed that in patients with difficult-to-control asthma, dupilumab can significantly decrease asthma exacerbations and improve respiratory symptoms and lung function. These effects were paralleled by significant reductions in T-helper 2-associated inflammatory biomarkers. However, further larger and longer trials are required to extend and validate these preliminary results, and to carefully study the safety and tolerability profile of dupilumab.