BOSTON -- Tezepelumab (Tezspire) significantly improves asthma-related sleep disturbances and activity levels in patients with severe, uncontrolled asthma, according to a post-hoc analysis of the phase III NAVIGATOR trial presented at the CHEST 2024 annual meeting.
Improved Sleep Quality
At 52 weeks, patients treated with tezepelumab were 40% to 62% more likely to report improvements in various sleep parameters compared to those receiving placebo, according to Dr. Njira Lugogo of the University of Michigan. These improvements included:
- Reduced limitations in sleep due to asthma (OR 1.50, 95% CI 1.15-1.95)
- Fewer instances of waking up in the morning with asthma symptoms (OR 1.62, 95% CI 1.25-2.11)
- Decreased nocturnal awakenings due to asthma (OR 1.40, 95% CI 1.08-1.82)
- Enhanced ability to get a good night's sleep despite asthma (OR 1.54, 95% CI 1.18-1.99)
Furthermore, 38% of patients on tezepelumab reported that coughing no longer disturbed their sleep, compared to 26% in the placebo group (OR 1.78, 95% CI 1.37-2.33).
Enhanced Activity Levels
In addition to sleep improvements, tezepelumab also demonstrated a positive impact on activity levels. A higher percentage of patients receiving tezepelumab reported improvements in symptoms during:
- 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)
Study Details and Considerations
The NAVIGATOR trial enrolled patients aged 12 to 80 years who were using medium- to high-dose inhaled corticosteroids and at least one other controller medication. Patients were randomized to receive tezepelumab or placebo via subcutaneous injection every 4 weeks. The post-hoc analysis included 528 patients in the tezepelumab group and 531 in the placebo group.
Dr. Subhakar Kandi of Kamineni Hospitals raised a crucial point regarding the potential influence of comorbid sleep disorders, such as sleep apnea, on the observed sleep improvements. He noted that without controlling for the effects of treatments for these conditions, it is challenging to determine the specific contribution of tezepelumab to the reported outcomes. Dr. Lugogo acknowledged that the analysis did not control for sleep apnea, which is a common comorbidity in severe asthma patients.
Mechanism of Action
Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin (TSLP), an epithelial cytokine involved in asthma pathogenesis. The FDA approved tezepelumab in 2021 as an add-on maintenance treatment for patients aged 12 and older with severe asthma. The primary analysis of the NAVIGATOR trial demonstrated that tezepelumab reduced the annualized rate of asthma exacerbations by more than half and improved lung function, asthma control, and health-related quality of life.
