Dupilumab Linked to Improved Outcomes in Those With T2 Asthma, Sleep Disturbance

Dupilumab was associated with significantly reduced nighttime symptoms and exacerbations and improved lung function and asthma control in patients with type 2 (T2) asthma and high sleep disturbance (HSD), according to study findings published in Respiratory Medicine.

Researchers assessed the efficacy of dupilumab in patients with moderate-to-severe T2 asthma and HSD, using data from the phase 3 QUEST trial (ClinicalTrials.gov Identifier: NCT02414854) for patients identified as having HSD and moderate to severe T2 asthma. Endpoints for the post hoc analysis included the proportion of patients with HSD according to a sleep composite endpoint, annualized severe exacerbation rates, and sleep-related and clinical outcomes at week 52.

In QUEST, participants (aged 12 years and older) were randomly assigned in a 2:2:1:1 ratio to receive subcutaneous dupilumab 200 mg or 300 mg or matched placebo every 2 weeks for 52 weeks. The current post hoc analysis focused on patients with moderate to severe type 2 asthma, which was considered as having a blood eosinophil count of at least 150 cells/µL and fractional exhaled nitric oxide (FeNO) of at least 25 ppb at baseline.

In the intention-to-treat cohort, 61% of participants (n=1,165/1,902) had HSD at baseline, defined by the sleep composite endpoint from validated patient-reported outcomes (PROs). In the post hoc analysis, 500 of the 782 patients with T2 asthma at baseline (64%) met the criteria for HSD; among the 445 patients with T2 asthma and an ACQ-5 of at least 2.5 at baseline, the percentage of those with HSD was even higher (81%; n=364/445, of whom 235 received dupilumab and 129 received placebo).

Dupilumab reduced the proportion of patients with HSD and T2 asthma (and baseline ACQ-5 ≥2.5) from 81% to 30% by week 52. In those who received placebo, the proportion with HSD decreased from 84% at baseline to 49% at week 52. Improvement was significantly higher for the intervention group vs the placebo group (risk difference, -22.8; 95% CI, -33.02 to -12.57; P <.0001).

Dupilumab significantly reduced nighttime symptom scores compared with placebo (least squares [LS] mean difference, -0.31; 95% CI, -0.47 to -0.14; P =.0002) and decreased the number of nocturnal awakenings (LS mean difference: -0.17; 95% CI, -0.36 to 0.02; P =.0716). Dupilumab significantly decreased the ACQ-5 global score in the same patients at week 52 vs placebo (LS mean difference, -0.56; 95% CI, -0.81 to -0.32; P <.0001).

Dupilumab was associated with a significant decrease in annualized severe exacerbation rates by 66% in the intervention vs placebo groups and improved pre-bronchodilator forced expiratory volume in 1 second (FEV₁) by 0.34 L at week 52 (P <.0001). In addition, 37.6% of patients who received dupilumab reported that they no longer needed short-acting β-agonists at week 52 compared with 1.3% at baseline.

Among several limitations, the subgroup sample sizes may have been too small and not sufficiently powered to evaluate subgroup differences. In addition, the subjective nature of the outcomes assessed may have an unknown effect on the data as the psychometric properties of the items in the composite sleep endpoint have not been validated.

“Dupilumab reduced nighttime symptoms and exacerbations, and improved lung function, overall asthma control, and quality of life,” said researchers, who further noted that sleep-related items in asthma patient-reported outcome tools such as the ACQ may offer a useful tool for identifying patients with asthma who have HSD.

Disclosure: This research was sponsored by Sanofi and Regeneron Pharmaceuticals Inc. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on Pulmonology Advisor