Asthma control better with dupilumab-ICS combo

Adding the anti-interleukin-4 receptor alpha monoclonal antibody dupilumab to an inhaled corticosteroid (ICS) reduces asthma exacerbations and improves lung function in a post hoc analysis of the LIBERTY ASTHMA QUEST trial.

Compared with a high-dose ICS + placebo, dupilumab + a medium-dose ICS cut severe asthma exacerbations by 70 percent (0.273 vs 0.899 per year, p<0.0001). Throughout the trial, the proportion of patients who achieved asthma control increased gradually in both groups, but those on dupilumab had better results (64 percent vs 42 percent, odds ratio (OR, 2.27) at Week 12; 67 percent vs 45 percent (OR, 2.29) at Week 24, and 71 percent vs 51 percent (OR, 2.26) at Week 52). [AAAAI 2024, abstract L23]

“The better performance of the dupilumab-ICS combination in this trial suggests that high-dose ICS is not really that specific for the inflammatory component relating to disease expression,” said Dr William Busse from the University of Wisconsin School of Medicine and Public Health in Madison, Wisconsin, US. The surprising data is that it works, and the longer you take it, the better it is.”

Dupilumab met the primary endpoint, with a 47.7 percent lower annualized rate of severe asthma exacerbations and 0.32 L greater absolute change from baseline to week 12 in forced expiratory volume in 1 second (FEV₁) before bronchodilator compared with placebo.

LIBERTY ASTHMA QUEST trial included 1,902 patients who received a medium dose of ICS (500-1,000 µg/day) or a high dose (>1,000 µg/day) with an additional long-acting β2-agonist medication and could have a third controller at the time of baseline measurements.

The analysis included only the 513 patients who received a medium-dose ICS with 200/300 mg add-on of dupilumab every 2 weeks and the 287 patients who received a high-dose ICS with a volume-matched placebo.

Asthma control was assessed using the five-item Asthma Control Questionnaire. Control was defined as a score of <1.5. The researchers also measured severe exacerbation rates and least squares (LS) mean differences from baseline in pre-bronchodilator FEV₁.

At baseline, patients in the high-dose ICS group had an average FEV₁ of 1.71, whereas patients in the medium-dose ICS + dupilumab group had an average FEV1 of 1.91. Differences in LS mean change in FEV₁ from baseline significantly favoured patients treated with dupilumab at various time points (2, 12, and 24 weeks) and at 52 weeks (p<0.0001 for all).

Patients included in the LIBERTY ASTHMA QUEST trial were 12 years and older, with uncontrolled type 2 asthma (blood eosinophil count of ≥150 cells/mL or fractional exhaled nitric oxide of ≥20 ppb at baseline) and≥1 asthma exacerbation a year before study enrolment.

Busse said caution must be exercised when interpreting the data, as they were based on a post hoc analysis.