Dupilumab cuts exacerbation rates in patients with asthma regardless of lung function
Patients with moderate-to-severe asthma had significant reductions in annualized severe asthma exacerbation rate with the monoclonal antibody dupilumab, regardless of lung function, according to a post hoc analysis of LIBERTY ASTHMA QUEST* presented at ERS 2020.
A total of 1,902 patients (≥12 years) were included in the analysis. Participants were given subcutaneous dupilumab 200 or 300 mg (n=1,264) or matching placebos (n=638) every 2 weeks for 52 weeks. [ERS 2020, abstract 2268]
At week 12, 62 percent of dupilumab recipients achieved prebronchodilator (BD) FEV1** improvements of ≥100 mL, while 49 percent achieved improvements of ≥200 mL. The percentages of placebo recipients achieving pre-BD FEV1 improvements of ≥100 and ≥200 mL were 49 percent and 37 percent, respectively.
“[These findings show that] a greater proportion of patients with uncontrolled, moderate-to-severe asthma had clinically meaningful improvements in pre-BD FEV1 (≥100 or ≥200 mL) at week 12 when treated with dupilumab vs placebo,” said the researchers.
When stratified according to pre-BD FEV1 improvement, both dupilumab doses led to significant reductions in annualized severe asthma exacerbation rate in participants with pre-BD FEV1 improvement of ≥100 mL (–51 percent; p<0.001 [200 mg] and –37 percent; p<0.01 [300 mg]).
The lack of improvement in pre-BD FEV1 did not appear to influence the results, as the annualized rate of severe asthma exacerbations among those without pre-BD FEV1 improvement still dropped significantly with both dupilumab doses vs placebo (–36 percent [200 mg] and –38 percent [300 mg]; p<0.01 for both).
The reductions in annualized severe asthma exacerbation rate were similarly observed among subjects with (–54 percent; p<0.001 [200 mg] and –46 percent; p<0.01 [300 mg]) and without pre-BD FEV1 improvement of ≥200 mL (–35 percent [200 mg] and –36 percent [300 mg]; p<0.01 for both), both favouring dupilumab over placebo.
In a subgroup of patients with elevated baseline biomarkers for type 2 inflammation***, the annualized severe asthma exacerbation rates were almost halved with both dupilumab doses vs placebo among participants with (–51 percent [200 mg] and –47 percent [300 mg]) and without pre-BD FEV1 improvement of ≥100 mL (–49 percent and –57 percent, respectively; p<0.0001 for all). The results were similar among those with (–51 percent; p<0.01 [200 mg] and –55 percent; p<0.0001 [300 mg]) and without pre-BD FEV1 improvement of ≥200 mL (–48 percent and –53 percent, respectively; p<0.0001 for both).
The subgroup findings suggest that dupilumab benefited patients exhibiting factors that may greatly contribute to the development of asthma exacerbations. [Front Immunol 2018;doi:10.3389/fimmu.2018.02220]
The incidence of treatment-emergent adverse events (AEs) were similar between the dupilumab and the placebo arms. The most common AEs reported were viral upper respiratory tract infection (18.2 percent vs 19.6 percent), injection-site erythema (13.8 percent vs 5.5 percent), upper respiratory tract infection (11.6 percent vs 13.6 percent), and bronchitis (11.4 percent vs 14.0 percent).
Although low pre-BD FEV1 is tied to increased exacerbation rate, lung function decline, difficult-to-treat disease, and increased mortality risk, the findings demonstrated the ability of dupilumab to reduce annualized severe asthma exacerbation rates up to half, even among those without clinically meaningful improvements in lung function, the researchers highlighted.
The current findings also reinforce the efficacy findings of the LIBERTY ASTHMA QUEST trial that have been previously reported. [ATS 2019, abstract A2667/P502]
*LIBERTY ASTHMA QUEST: Evaluation of dupilumab in patients with persistent asthma
**FEV1: Forced expiratory volume in 1 second***Blood eosinophils ≥150 cells/µL and/or fractional exhaled nitric oxide ≥25 parts per billion