Effect of Dupilumab on Sleep Disturbance in Patients With Uncontrolled Moderate-to-Severe Asthma, Type 2 Inflammation, and Nocturnal Awakenings: The MORPHEO Randomized Controlled Trial

BACKGROUND: This study was performed to evaluate the effects of dupilumab on sleep disturbance in adults with uncontrolled moderateto-severe asthma in the phase 4 MORPHEO study (NCT04502862). PATIENTS AND METHODS: The study population comprised adults (18-65 years) with uncontrolled (Asthma Control Questionnaire [ACQ] 5 score ≥2.5), type 2 (baseline eosinophils ≥150/μL and fractional exhaled nitric oxide [FeNO] ≥25 ppb), moderate-to-severe-asthma, and frequent nocturnal awakenings (≥1/night average). Patients were randomized 1:1 to receive dupilumab 200 mg or placebo every 2 weeks for 12 weeks. The primary endpoint was change from baseline to week 12 in the Asthma Sleep Disturbance Questionnaire (ASDQ) score. Other endpoints included changes from baseline in nocturnal awakenings, sleep quality, restorative sleep, wakefulness after sleep onset (WASO), prebronchodilator forced expiratory volume in 1 second (FEV1), ACQ-7 score, and FeNO. RESULTS: Of the 202 patients included, 185 (91.6%) completed the intervention. The primary endpoint was not met. Groups differed nonsignificantly at week 12 in terms of the improvement in the ASDQ score (least squares mean difference [standard error], -0.07 [0.107]; P=.512) and did not differ in terms of the decrease in the number of nocturnal awakenings (0.00 [0.110]; 95%CI, -0.21 to 0.22). Both arms improved in the secondary sleep-diary endpoints sleep quality (0.17 [0.211]; 95%CI, -0.24 to 0.59), restorative sleep (0.13 [0.212]; 95%CI, -0.29 to 0.54), and WASO (-4.10 [5.510]; 95%CI, -14.99 to 6.79) at week 12. Compared with placebo, dupilumab improved prebronchodilator FEV1, ACQ-7, and FeNO. The results were nominally statistically significant. CONCLUSION: Although most sleep outcomes improved comparably in the groups, dupilumab (vs placebo) improved asthma symptoms, lung function, and airway inflammation in adults with uncontrolled, type 2, moderate-to-severe asthma and frequent nocturnal awakenings.