Introduction and objectives Dupilumab, a fully human anti-interleukin (IL)−4α monoclonal antibody that inhibits IL-4 and IL-13, key drivers of Type 2 inflammation, is approved for treatment of adults with inadequately controlled moderate-to-severe atopic dermatitis. In a double-blind, placebo-controlled phase 3 study (NCT02414854), patients with asthma aged ≥12 years, without a minimum baseline eosinophil requirement and uncontrolled with medium-to-high-dose inhaled corticosteroids (ICS) plus up to two additional controllers, received add-on dupilumab 200 mg or 300 mg or matched placebo every 2 weeks (q2w) for 52 weeks. In the overall intent-to-treat population, both dupilumab doses significantly reduced annualized severe exacerbation rates during the 52 week treatment period, improved pre-bronchodilator forced expiratory volume in 1 s (FEV₁), improved quality of life measures, and were generally well tolerated. This pre-specified analysis assessed the efficacy of dupilumab by disease severity determined by baseline ICS dose (high/medium).

Methods Annualized severe exacerbation rates during the 52 week treatment period and change from baseline in pre-bronchodilator FEV₁ at Week 12 were analyzed by baseline ICS dose (high/medium) subgroup. These parameters were further analyzed by subgroups defined by baseline levels of eosinophils (≥300 cells/µL) and fractional exhaled nitric oxide levels (FeNO;≥25 ppb).

Results Both dupilumab q2w doses significantly reduced annualized severe exacerbation rates over the 52–week treatment period (p<0.01) compared to placebo and improved pre-bronchodilator FEV₁ at Week 12 (p<0.01) regardless of baseline ICS dose (figure 1). Overall, reduction in exacerbation rate and improvement in FEV₁ appeared similar between high- and medium-dose ICS subgroups with increased efficacy in subgroups with baseline eosinophil levels of ≥300 cells/µL (both p<0.01) or baseline FeNO level of ≥25 ppb (both p<0.01). The most frequent adverse event occurring at higher frequency in the dupilumab groups vs placebo was injection-site reaction (15%/18% vs 5%/10%, respectively).

Conclusions Add-on dupilumab significantly reduced the rate of severe exacerbations, and improved FEV₁ in patients with moderate or severe asthma (as assessed by medium or high ICS dose at baseline). Dupilumab demonstrated increased efficacy in patients with higher levels of Type 2 inflammation, as defined by elevated baseline eosinophil counts and FeNO levels. Dupilumab was generally well tolerated.

Please refer to page A265 for declarations of interest related to this abstract.

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Abstract S78 Figure 1

Change from baseline to week 12 in pre-bronchodilator FEV₁ (L) and annualized severe exacerbation rates during the 52-week treatment period in patients with high/medium baseline ICS dose and with high baseline blood eosinophils (≥300 cells/µL) and FeNO levels (≥25 ppb) treated with dupilumab vs placebo