Tezepelumab Enhances Sleep and Physical Activity for Patients with Severe Asthma

Tezepelumab significantly improves patient-reported outcomes beyond traditional respiratory metrics, specifically targeting sleep disturbances and physical activity levels in those with severe uncontrolled asthma (SUA), according to a study published in Annals of Allergy, Asthma & Immunology.¹

“A substantial number of patients with severe asthma have symptoms that remain uncontrolled despite treatment with optimal inhaled therapies,” wrote authors of the study. “SUA impacts patients’ overall health-related quality of life (HRQoL) due to reduced lung function, reduced overall activity levels, and increased severe asthma exacerbations and sleep disturbances (such as early morning awakenings and difficulty initiating and maintaining sleep), thereby contributing to a significant burden on patients and their family members.”

For pharmacists managing complex respiratory regimens, these findings are particularly relevant as they highlight tezepelumab’s efficacy in the high-burden subpopulation of patients who also suffer from comorbid chronic rhinosinusitis with nasal polyps (CRSwNP).

READ MORE: AstraZeneca's Breztri Aerosphere Shows Improvement in Uncontrolled Asthma

This analysis, derived from the phase 3 NAVIGATOR (NCT03347279) study, demonstrates that blocking thymic stromal lymphopoietin (TSLP) provides meaningful relief from the day-to-day symptomatic burdens that often persist despite maximal inhaled therapy.

The concept of unified airway disease is central to understanding why these comorbid patients represent such a difficult-to-treat demographic. This framework posits that the upper and lower airways function as a single immunological unit, frequently sharing type-2 inflammatory pathways driven by epithelial cytokines like TSLP.^1,2

Pharmacists should note that patients with both conditions often experience worse sleep quality and greater difficulty with physical exertion than those with either condition alone. The current study highlights that tezepelumab, a human monoclonal antibody, addresses this by blocking TSLP from interacting with its receptor, thereby dampening the upstream inflammatory response.¹

In the NAVIGATOR trial, 1059 patients with SUA were randomized to receive either 210 mg of tezepelumab or a placebo subcutaneously every 4 weeks. The post-hoc analysis specifically looked at responses to the Asthma Quality of Life Questionnaire and the St. George’s Respiratory Questionnaire, focusing on sleep quality, activity levels, and physical exertion tolerance.

Results showed that tezepelumab recipients were significantly more likely to shift from limited to nonlimited status in their daily activities compared with the placebo group. Remarkably, these improvements were even more pronounced in the subpopulation with a history of CRSwNP. For instance, the odds of improving shortness of breath from walking up hills were over 12 times higher for tezepelumab recipients in the CRSwNP group than for those who took the placebo.

Broadening the clinical context, a comprehensive meta-analysis of 16 randomized controlled trials involving over 3500 patients further supports the use of biologics in this comorbid population, according to the European Respiratory Review.² This research found that biologics as a class reduce annual asthma exacerbations by 73% and improve forced expiratory volume in one second (FEV1) by a clinically meaningful 0.21 liters.

While anti-IL-5 and anti-IL-5Ra agents like mepolizumab and benralizumab are highly effective at reducing exacerbations and improving lung function, the anti-TSLP pathway targeted by tezepelumab showed the greatest numerical improvements in specific QOL metrics, including the Asthma Quality of Life Questionnaire and nasal congestion scores.

The evidence for tezepelumab’s efficacy extends directly into the treatment of CRSwNP itself, as evidenced by the WAYPOINT study. In this trial, adults with severe, uncontrolled CRSwNP who received tezepelumab saw significant reductions in nasal polyp size and nasal congestion severity compared with those receiving standard care plus a placebo, according to a study from the New England Journal of Medicine.³

For the pharmacy team, these findings underscore the importance of identifying severe asthma patients with comorbid upper airway disease. Patients with CRSwNP in the NAVIGATOR study tended to have higher baseline eosinophil counts and fractional exhaled nitric oxide levels, suggesting a more intense inflammatory state.

Despite the availability of other biologics like dupilumab, omalizumab, and reslizumab—which also target type 2 inflammation—tezepelumab’s unique upstream intervention offers a promising alternative for those who remain symptomatic.

By improving sleep quality and physical exertion tolerance, this therapy addresses the Achilles heel of asthma care: the persistent daily symptoms that prevent patients from working, sleeping, or exercising normally.^1,2,4

“Tezepelumab treatment led to a higher proportion of patients with SUA reporting better sleep, activity levels, and physical exertion tolerance compared with placebo,” concluded authors of the study.¹ “Patients with a history of comorbid CRSwNP showed greater improvements than those without. These results support the efficacy of tezepelumab in patients with SUA overall and with comorbid CRSwNP.”

READ MORE: Asthma Resource Center

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REFERENCES

1. Lugogo NL, Han JK, Peters AT, et al. Tezepelumab’s effects on patient-reported symptoms in severe asthma, overall and with history of comorbid CRSwNP. Ann Allergy Asthma Immunol. February 13, 2026. https://doi.org/10.1016/j.anai.2026.02.002

2. Kyriakopoulos C, Ntritsos G, Gogali A, et al. Efficacy of biologic agents in patients with comorbid asthma and chronic rhinosinusitis with nasal polyps: a systematic review and meta-analysis of randomised controlled trials. Eur Respir Rev. 2026 Jan 14;35(179):250186. doi: 10.1183/16000617.0186-2025.

3. Lipworth BJ, Han JK, Desrosiers M, et al. Tezepelumab in adults with severe chronic rhinosinusitis with nasal polyps. N Engl J Med. 2025 Mar 27;392(12):1178-1188. doi: 10.1056/NEJMoa2414482. Epub 2025 Mar 1.

4. Asthma. Cleveland Clinic. June 18, 2025. Accessed February 23, 2026. https://my.clevelandclinic.org/health/diseases/6424-asthma