Dupilumab had a greater effect in patients with more severe asthma with a higher type 2 inflammatory signature.
Dupilumab reduces severe asthma exacerbations and improves lung function and asthma control in patients with type 2 asthma receiving high-dose corticosteroids (ICS) at baseline, according to study findings published in Respiratory Medicine.
Investigators conducted a post-hoc analysis of the phase 3 QUEST study (ClinicalTrials.gov identifier: NCT02414854) to assess the effects of dupilumab in a subpopulations of patients with a type 2 inflammatory asthma phenotype (ie, baseline blood eosinophils ≥150 cells/μL or functional exhaled nitric oxide [FeNO] ≥25 ppb) who were receiving high-dose ICS at baseline.
Dupilumab is a monoclonal antibody that blocks interleukin-4 (IL-4) and IL-13. Study endpoints of the current post-hoc analysis included the following: (1) the annualized severe exacerbation rate, which was defined as the number of severe exacerbations per patient-year over the 52-week treatment period; (2) least squares (LS) mean change in prebronchodilator forced expiratory volume in 1 second (FEV1) from baseline at week 12 and over the treatment period; and (3) LS mean change in the 5-item Asthma Control Questionnaire (ACQ-5) score from baseline at week 24.
To further evaluate the efficacy of dupilumab across subpopulations, the researchers examined each endpoint in the subpopulations, defined according to the following baseline characteristics: (1) evidence of an allergic phenotype; (2) self-reported comorbid chronic rhinosinusitis and/or nasal polyposis; (3) prebronchodilator FEV1/forced vital capacity (FVC) ratio; (4) number of asthma exacerbations in the year prior to QUEST; (5) prebronchodilator FEV1; (6) age at asthma onset; (7) FEV1 reversibility; (8) body mass index; and (9) sex. The analysis also was performed in patients with baseline eosinophils of at least 150 cells/μL or FeNO of at least 25 ppb who were receiving medium-dose ICS at baseline.
Results of the study showed that dupilumab treatment was associated with reduced exacerbations and improved prebronchodilator FEV1 at week 12, as well as with improved ACQ-5 scores at week 24, across subgroups of participants with type 2 asthma receiving high-dose ICS at baseline. Treatment with dupilumab was effective in participants receiving medium-dose ICS as well. 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.
A key limitation of the current study is the small sample size of certain subgroups, including the subgroups of patients who had experienced at least 3 or 4 exacerbations in the year prior to QUEST, as well as those with baseline eosinophil levels of at least 300 cells/μL to 500 cells/μL. Because subgroups were not defined a priori, the study was not powered specifically to investigate differences between patients with high-dose and medium-dose ICS use at baseline in these specific subpopulations. Further, researchers lacked information on patient adherence to ICS.
“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,” the study authors concluded.
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.
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. 2022;202:106938.