Dupilumab improves late-onset asthma outcomes

Treatment with dupilumab, a fully human monoclonal antibody that inhibits interleukin (IL)-4 and IL-13 signalling, significantly reduces severe exacerbation rate and improves lung function in patients with late-onset asthma, according to results of a post hoc analysis of the Liberty Asthma Quest* trial presented at ATS 2019.

Of the 1,902 patients with uncontrolled, moderate-to-severe asthma who were randomly assigned to receive add-on dupilumab 200 or 300 mg subcutaneously every 2 weeks or a matching placebo for 52 weeks in Liberty Asthma Quest, 533 patients with late-onset asthma were included in the current post hoc analysis. The analysis stratified patients (>40 years of age) based on their baseline post-bronchodilator FEV₁/FVC** ratios (<0.7 L; n=308 or ≥0.7 L; n=225). [ATS 2019, abstract A2667/P502]

Among late-onset asthma patients with fixed airway obstruction (baseline post-bronchodilator FEV₁/FVC <0.7 L), those who received dupilumabhad a significantly reduced rate of severe exacerbations compared with placebo (relative risk [RR], 0.48 vs 1.53; p<0.001 for 200 mg or 0.33 vs 1.34; p<0.001 for 300 mg).

A lower rate of severe exacerbation was also observed among patients without fixed airway obstruction (baseline post-bronchodilator FEV₁/FVC ≥0.7 L) in the dupilumab arm than the placebo arm (0.37 vs 0.82; p<0.05 for 200 mg or 0.37 vs 0.75; p<0.05 for 300 mg).

“Dupilumab200 and 300 mg significantly reduced severe exacerbations in uncontrolled, moderate-to-severe asthma patients with age at onset of asthma >40 years, both in the presence or absence of fixed airflow obstruction,” said study author Dr Nicola Hanania from Baylor College of Medicine in Houston, Texas, US.

However, the benefit of dupilumab vs placebo was greater among patients with fixed airway obstruction than those without (reduction in exacerbation rate, 69.0 percent vs 55.0 percent for 200 mg and 76.0 percent vs 51.0 percent for 300 mg).

At 52 weeks, patients with fixed airway obstruction treated with dupilumab vs placebo had improved pre-bronchodilator FEV₁(p<0.05 and p=0.09 for 200 and 300 mg, respectively) and post-bronchodilator FEV₁ratios (p<0.05 and p=0.06 for 200 and 300 mg, respectively). “Lung function improvements were observed … in patients with late-onset asthma and fixed airway obstruction, who typically experience worse asthma outcomes than those without fixed airway obstruction,” said Hanania.

In addition, those with fixed airway obstruction also showed a remarkably improved pre-bronchodilatorFEV₁/FVC and forced expiratory flow rate at 25–75 percent with either doses of dupilumab compared with placebo.

Upper respiratory tract infection (18 percent vs 20 percent), injection-site erythema (14 percent vs 6 percent), upper respiratory tract infection (12 percent vs 14 percent), and bronchitis (11 percent vs 14 percent) were the most common treatment-emergent adverse events reported in the dupilumab and the placebo treatment groups.

“The magnitude of effect with dupilumab, for several outcome measures in patients with age at onset of asthma >40 years was consistently greater in patients with a reduced post-bronchodilatorFEV₁/FVC,” the researchers said.

*Liberty Asthma Quest: Evaluation of dupilumab in patients with persistent asthma 

**FEV₁/FVC: Forced expiratory volume in 1 second/forced vital capacity