Dupilumab Reduces Nighttime Symptoms, Sleep Disturbance in Severe T2 Asthma

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In patients with poorly controlled moderate to severe type 2 asthma and high sleep disturbance (HSD), treatment with dupilumab (Dupixent; Regeneron Pharmaceuticals, Sanofi) was associated with a reduction in HSD from 81% to 31% over a follow-up period of 52 weeks. Dupilumab treatment, compared with placebo, also significantly reduced nighttime symptoms and asthma exacerbations and led to improved lung function, disease control, and health-related QoL.

The findings, from a recent post-hoc analysis of the QUEST randomized clinical trial and published in Respiratory Medicine, showed further that at 52 weeks of treatment with dupilumab, 37.6% of participants reported they "no longer needed" to use their short acting beta agonist (SABA) medications vs just 1.3% who said the same at study baseline. Among those treated with placebo, 24.5% said they did not need to use a rescue inhaler at week 52 vs 5.4% who said they didn't need it at baseline.

Dupilumab-treated participants experienced a 66% reduction in yearly severe asthma exacerbations and demonstrated an improvement in pre-bronchodilator forced expiratory volume in 1 second of 0.34L at 52 weeks.

Respiratory disturbances during sleep are common among persons with asthma and are associated with poor sleep quality, daytime sleepiness, deteriorating asthma control, and potentially with a range of social and neurobehavioral sequelae, Jorge F. Maspero, MD, director for allergy and respiratory medicine at Fundación Cidea, Buenos Aires, Argentina, and colleagues wrote. Yet despite the known negative impacts of asthma-related sleep issues on overall disease management, clinicians do not have access to a simple and effective tool to assess the effects, according to the authors. .

The 5-item Asthma Control Questionnaire (ACQ-5) is used clinically to assess asthma control and response to treatment and also includes items that query sleep impairment. In this analysis of QUEST-3, the researchers identified participants with HSD and then explored the utility of the ACQ-5 as a single tool to identify participants more likely to have HSD. The second study aim was to evaluate the impact of dupilumab for 52 weeks on nighttime asthma symptoms, ACQ-5 score, annualized severe exacerbation rates, lung function, and SABA use.

The investigators identified 364 participants in the QUEST study cohort with type 2 asthma who had a baseline ACQ-5 score≥2.5 and were classified as having HDS. Of this group, 235 patients received dupilumab (mean age 46.5 years, 66% women) and 129 received placebo (48.1 years, 67.4% women).

In addition to reduction in prevalence of HSD, dupilumab treatment at 52 weeks was associated with a reduction in nighttime symptom scores, the number of nocturnal awakenings, participant’s global ACQ-5 score, and global Asthma Related Quality-of-Life Questionnaire score,Maspero et al reported.

Further, only 10.7% of participants in the dupilumab group reported needing 5 or more puffs/inhalations of SABA daily at week 52 vs 35.7% reporting the need at baseline, a greater improvement than among placebo treated participants among whom 21.4% reported needing 5 or more puffs at week 52 compared with 36.4% at baseline.

“These results suggest a potential association between reported [high sleep disturbance] and poor asthma control as measured by the ACQ-5, supporting the sleep-related items of the asthma [patient reported outcomes] as a useful tool to identify [high sleep disturbance] among the asthma population,” Maspero and colleagues wrote. “Future research is needed to further explore and validate this hypothesis.”

Source: Maspero JF, Shafazand S, Cole J, et al. Dupilumab efficacy in high sleep disturbance management among patients with type 2 asthma. Resp Med. 2023;218. doi:10.1016/j.rmed.2023.107344