Dupilumab reduces exacerbations in type 2 asthma regardless of ICS dose

Treatment with dupilumab significantly reduced the annual rate of severe exacerbations in children with uncontrolled, moderate-to-severe type 2 asthma who were on high- or medium-dose inhaled corticosteroid (ICS), according to a study presented at PAS 2024.

“For patients with uncontrolled asthma with medium-dose ICS/LABA*, the current Global Initiative for Asthma (GINA) guidelines suggests escalating to high-dose ICS/LABA or addition of LAMA** before considering add-on biologic therapy,” said Dr Erik Orava from Sanofi, Mississauga, Ontario, Canada.

Hence, Orava and his team sought to evaluate the efficacy of dupilumab in children with type 2 asthma stratified by high- or medium-dose ICS based on GINA 2015 criteria.

This study included children aged 6 to <12 years with type 2 asthma (baseline blood eosinophils ≥150 cells/μL or FeNO*** ≥20 parts per billion [ppb]) enrolled in the phase III LIBERTY ASTHMA VOYAGE study. Patients were randomized to receive subcutaneous dupilumab 100 or 200 mg every 2 weeks or placebo, in addition to standard therapies, for 52 weeks. A total of 152 children received high-dose ICS, while 195 children received medium-dose ICS.

At week 52, children treated with dupilumab achieved a significantly reduced annualized rate of severe asthma exacerbation than those treated with placebo in both high- (relative risk [RR], 0.37; p<0.001) and medium-dose (RR, 0.41; p<0.01) ICS groups. [Orava E, et al, PAS 2024]

Additionally, a higher percentage of dupilumab-treated patients were free of severe exacerbations compared with the placebo-treated patients in both ICS dosing groups (69.6 percent vs 52 percent [high dose] and 82.4 percent vs 65.6 percent [medium dose]).

At week 12, lung function, as assessed by prebronchodilator (pre-BD) ppFEV₁⁺, was significantly improved with dupilumab vs placebo in the medium-dose ICS group (least square [LS] mean difference, 7.23; p<0.001).

Although not significant in the high-dose ICS group, dupilumab recipients also achieved an improved pre-BD ppFEV₁ at week 12 compared with the placebo recipients (LS mean difference, 2.64)

The dupilumab arm also exhibited improved asthma control, as shown by a reduction in ACQ-7-IA⁺⁺ scores at week 12, compared with the placebo arm (LS mean difference, -0.37; p<0.01 [high dose] and -0.33 [medium dose]).

In a subgroup of patients with baseline blood eosinophils ≥150 and ≥300 cells/μL as well as FeNO level ≥20 ppb, a consistent trend toward lower exacerbation rates and improved lung function and asthma control was observed with dupilumab over placebo, regardless of ICS dose, Orava noted.

“Overall, the exacerbation reduction observed in children with uncontrolled, moderate-to-severe type 2 asthma treated with dupilumab was significant regardless of the ICS dose across all subgroups,” he concluded.