Effect of Dupilumab in Korean Patients With Uncontrolled Moderate-to-Severe Asthma: A LIBERTY ASTHMA QUEST Sub-analysis

Abstract

Purpose: To assess the effect of dupilumab on the annualized severe exacerbation rates, change in forced expiratory volume at first second (FEV1), overall asthma control and health-related quality of life in Korean patients from the LIBERTY ASTHMA QUEST study.

Methods: Of the 1,902 patients enrolled in the LIBERTY ASTHMA QUEST study, a phase-3, randomized, double-blind, placebo-controlled, parallel-group study on dupilumab, 74 (4%) were Korean. The patients were randomly assigned to 4 treatment groups (2:2:1:1). The sub-analysis reported herewith was performed with the pooled groups of dupilumab and placebo from the 4 original treatment groups in the LIBERTY ASTHMA QUEST study. The efficacy endpoints were annualized rate of severe exacerbation events during the 52-week study period and changes from baseline in pre-bronchodilator FEV1 in week 12. Asthma control, asthma quality of life and the effect of treatment on the levels of type 2 inflammatory biomarkers were assessed. The safety profile was also evaluated.

Results: In Korean patients, annualized severe exacerbation rates were reduced with dupilumab (n = 49) compared to placebo (n = 25) (0.259 vs 1.942) during the 52-week treatment period. The relative risk reduction with dupilumab was 87% (P < 0.001). Improvements in pre-bronchodilator FEV1 (mean difference of 0.24 L, P = 0.021) were observed in week 12 in dupilumab-treated patients. Additionally, improvements in asthma control and asthma-related quality of life were observed; the FeNO and serum immunoglobulin E levels were reduced. The incidence of adverse events and serious adverse events was comparable between the dupilumab and placebo group. A total of 11 patients from the dupilumab group reported 63 injection site reactions.

Conclusions: Dupilumab, as an add-on therapy in severe asthma, is efficacious and has an acceptable safety profile in Korean patients.

Trial registration: ClinicalTrials.gov Identifier: NCT02414854.

Keywords: Exacerbation; asthma; biological products; forced expiratory volume; quality of life; randomized controlled trial.

Fig. 1. Reduction of annualized rate of severe exacerbations during the 52-week intervention period in (A) the Korean ITT population, (B) patients with the baseline blood eosinophil ≥ 150 cells/μL, and (C) patients with the baseline FeNO ≥ 25 ppb, for dupilumab vs. placebo.

ITT, intention-to-treat; CI, confidence interval; FeNO, fractional exhaled nitric oxide; ppb, parts per billion.

Fig. 2. Magnitude of changes from the baseline in pre-bronchodilator FEV1 in week 12 in (A) the Korean ITT population, (B) patients with the baseline blood eosinophil ≥ 150 cells/μL, and (C) patients with the baseline FeNO ≥ 25 ppb, for dupilumab vs. placebo.

ITT, intention-to-treat; FEV1, forced expiratory volume at first second; LS, least squares; SE, standard error; FeNO, fractional exhaled nitric oxide; ppb, parts per billion.

Fig. 3. Changes from the baseline in pre-bronchodilator FEV1 during the 52-week intervention period in (A) the Korean ITT population, (B) patients with the baseline blood eosinophil ≥ 150 cells/µL, and (C) patients with the baseline FeNO ≥ 25 ppb for both dupilumab doses vs. both placebos combined.

LS, least squares; SE, standard error; FEV1, forced expiratory volume in 1 second; FeNO, fractional exhaled nitric oxide; ITT, intention-to-treat. ^*P ≤ 0.0001; ^†P ≤ 0.001; ^‡P ≤ 0.05.

Fig. 4. Changes from the baseline in total asthma control (ACQ-5) scores during the 52-week intervention period in (A) the Korean ITT population, (B) patients with the baseline blood eosinophil ≥ 150 cells/µL, and (C) patients with the baseline FeNO ≥ 25 ppb for both dupilumab doses vs. both placebos combined.

LS, least squares; SE, standard error; ACQ-5, 5-item asthma control questionnaire; ITT, intention-to-treat; FeNO, fractional exhaled nitric oxide. ^*P < 0.001; ^†P < 0.05 vs. matched placebo.

Fig. 5. Changes from the baseline in asthma-related quality of life (AQLQ) scores during the 52-week intervention period in (A) the Korean ITT population, (B) Patients with the baseline blood eosinophil ≥ 150 cells/µL, and (C) Patients with the baseline FeNO ≥ 25 ppb for both dupilumab doses vs. both placebos combined.

LS, least squares; SE, standard error; AQLQ(S), Standardized Asthma Quality of Life Questionnaire; ITT, intention-to-treat; FeNO, fractional exhaled nitric oxide.