Dupilumab Reduces Severe Exacerbations, Improves Lung Function in Type 2 Asthma

Treatment with the interleukin-4 receptor antagonist dupilumab improves severe asthma exacerbation rates, lung function, and disease control in patients with type 2 asthma using high-dose inhaled corticosteroid (ICS). These were among study findings published in the journal Respiratory Medicine.

Given the heterogeneity of asthma, researchers recognize the importance of determining the effects of add-on biologic therapy in different subpopulations of patients with characteristics rendering them more or less responsive to standard treatment. Researchers for the current study therefore evaluated the efficacy and safety of dupilumab in several subgroups, including patients with type 2 asthma as well as those using high-dose ICS.

The evaluation was conducted via a post hoc analysis of the QUEST study (ClinicalTrials.gov identifier: NCT02414854), a phase 3, multinational, randomized controlled trial which showed that add-on dupilumab 200 mg and 300 mg every 2 weeks was associated with reductions in severe asthma exacerbations and improvements in prebronchodilator forced expiratory volume in 1 second (FEV₁).

Primary outcomes of the post hoc analysis of QUEST were: (1) adjusted annualized severe exacerbation rates over the treatment period; (2) least squares (LS) mean change from baseline at week 12 in prebronchodilator FEV₁; and (3) LS mean change from baseline at week 24 in the 5-item Asthma Control Questionnaire (ACQ-5) scores. These outcomes were evaluated in subgroups of patients being treated with high-dose (>500 μg) ICS with baseline blood eosinophil counts of at least 150 cells/μL and fractional exhaled nitric oxide (FeNO) levels of at least 25 ppb.

For the analysis, patients were divided into subgroups based on clinical and demographic characteristics and varying markers of asthma severity, including: (1) evidence of an allergic phenotype (with/without); (2) self-reported comorbid chronic rhinosinusitis and/or nasal polyposis (CRS/NP; with/without); (3) prebronchodilator FEV₁/forced vital capacity (FVC) ratio (<70% and ≥70%); (4) blood eosinophil levels (≥150 cells/μL, ≥300 cells/μL, and ≥500 cells/μL,); (5) number of exacerbations in the year prior to the QUEST study (≥1/≥2/≥3/≥4); (6) prebronchodilator FEV₁ (</≥ median value); (7) age at onset of asthma (≤40 years/>40 years); (8) FEV₁ reversibility (</≥ median value); (9) body mass index (<30 kg/m²/≥30 kg/m²); and (10) sex (male/female).

Results of the analysis showed that treatment with dupilumab reduced asthma exacerbations, improved prebronchodilator FEV₁ at week 12, and improved ACQ-5 scores at week 24 across subgroups of patients with type 2 asthma and high-dose ICS use at baseline.

A key limitation of the present study is the small sample size of certain subgroups, including patients who experienced at least 3 or 4 exacerbations in the year prior to QUEST, as well as those with baseline eosinophil counts of at least 300 cells/μL or 500 cells/μL. Another limitation was the lack of information available on patient adherence to ICS and the self-reported diagnosis of CRS/NP.

The researchers concluded that “While dupilumab demonstrated efficacy across a broad range of demographic and disease characteristics, the magnitude of effect tended to be greater in patients who had higher type 2 inflammatory signatures and features of more severe disease.”

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Bourdin A, Virchow JC, Papi A, et al. Dupilumab efficacy in subgroups of type 2 asthma with high-dose inhaled corticosteroids at baseline. Respir Med. Published online
August 11, 2022. doi:10.1016/j.rmed.2022.106938