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BOSTON -- Patients with severe, uncontrolled asthma had significantly higher odds of improvement in asthma-related sleep disturbances and improvement in activity levels when treated with tezepelumab (Tezspire), a post-hoc analysis of the phase III NAVIGATOR trial showed.

At 52 weeks, patients on tezepelumab were 40% to 62% more likely than placebo recipients to report improvements in sleep limitations, in waking up in the morning or night, and in getting a good night's sleep due to their asthma symptoms, reported Njira Lugogo, MD, of the University of Michigan in Ann Arbor.

Patients assigned to the biologic were also less likely to say that coughing disturbed their sleep at 52 weeks, and more likely to report improvements in symptoms during strenuous activity, according to findings presented at the CHEST 2024 annual meeting, hosted by the American College of Chest Physicians.

"Patients with severe asthma often have decreases in overall activity levels and sleep disturbance, and many of our patients are really bothered by these symptoms," Lugogo told attendees. "Many of us are very interested in patient-reported outcomes because they're the most meaningful in terms of patient quality of life."

Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin (TSLP), an epithelial cytokine involved in asthma pathogenesis. In the primary analysis of the phase III NAVIGATOR trial, tezepelumab decreased the annualized rate of asthma exacerbations by more than half in patients with severe, uncontrolled asthma, and also improved lung function, asthma control, and health-related quality of life.

The FDA approved the first-in-class biologic in 2021 as an add-on maintenance treatment for patients ages 12 and older with severe asthma.

Session moderator Subhakar Kandi, MBBS, MD, of Kamineni Hospitals in Hyderabad, India, asked if Lugogo and investigators controlled for the impact of sleep apnea and its treatment in the study population.

"Most of our severe asthma patients have comorbid sleep apnea," Lugogo acknowledged. "They were not excluded on the basis of that" and the analysis did not control for sleep apnea, she said.

"We were just looking at symptoms that seem to be more related to asthma -- cough, nocturnal awakenings, early morning symptoms -- which tend to be a little bit different from the ones related to sleep apnea," she explained, "But sometimes it's hard to disentangle that."

Without considering potential effects of treatments for sleep apnea and other comorbid sleep disorders on outcomes, "it's difficult to tell why a patient's sleep is improving," Kandi told 番茄社区. "Is it the CPAP machine or is it this molecule?"

enrolled patients ages 12 to 80 years (mean 49.5) using medium- to high-dose inhaled corticosteroids for at least a year and at least one other controller medication. Patients were randomized to receive tezepelumab or placebo, both given by subcutaneous injection every 4 weeks.

The post-hoc analysis presented by Lugogo assessed the effect of tezepelumab on activity levels and sleep disturbance and included 528 patients in the tezepelumab group and 531 in the placebo group.

At week 52, a higher percentage of patients treated with tezepelumab went from "severe to some limitations" with sleep at baseline to "few or no limitations":

• Limitation in sleep due to asthma: 49% vs 39% in the placebo group (OR 1.50, 95% CI 1.15-1.95)
• Waking up in the morning with asthma symptoms: 43% vs 32% (OR 1.62, 95% CI 1.25-2.11)
• Woken up at night due to asthma symptoms: 51% vs 41% (OR 1.40, 95% CI 1.08-1.82)
• Asthma interferes with getting a good night's sleep: 49% vs 38% (OR 1.54, 95% CI 1.18-1.99)

This analysis used patient-reported answers to sleep-related items on the standardized version of the Asthma Quality of Life Questionnaire for patients ages 12 years or older (AQLQ[S]+12). Those who improved from a baseline score of 1-5 (severe to some limitation) to a score of 6-7 (little to no limitation) at 52 weeks were considered responders to treatment.

Patients were also asked to answer "true" or "false" to a St. George's Respiratory Questionnaire item, "coughing disturbs my sleep." At 52 weeks, 38% of patients receiving tezepelumab changed their answer from "true" at baseline to "false," compared with 26% in the placebo group (OR 1.78, 95% CI 1.37-2.33).

In terms of activity, higher percentages of patients receiving tezepelumab reported improvements in symptoms on the AQLQ(S)+12 during the following:

• Strenuous activity: 38% vs 28% with placebo (OR 1.54, 95% CI 1.17-2.02)
• Work/school activity: 40% vs 32% (OR 1.38, 95% CI 1.06-1.80)
• Overall range of activities: 40% vs 31% (OR 1.48, 95% CI 1.14-1.94)

However, the odds of improvement in moderate activities did not differ significantly between the tezepelumab and placebo groups.

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