- The study addressed the effectiveness and safety of tezepelumab in diverse, real-world severe uncontrolled asthma populations.
- The PASSAGE study was a 12-month, phase 4, single-arm, open-label trial involving 286 participants with severe uncontrolled asthma.
- Annualized asthma exacerbation rates decreased by 70% (95% CI: 63, 75), from 2.88 to 0.87, across diverse patient groups.
- The authors concluded that tezepelumab substantially reduced exacerbations and improved lung function and asthma control in this population.
- These findings suggest tezepelumab is effective for a broad range of severe uncontrolled asthma patients encountered in clinical practice.
Managing Severe, Uncontrolled Asthma in Diverse Patient Populations
Severe, uncontrolled asthma remains a significant clinical challenge, impacting patient quality of life and requiring complex management [1]. While biologic therapies have substantially advanced treatment by reducing exacerbations and improving lung function [2, 3], their initial clinical trials often involved highly selected patient cohorts. This has raised questions about effectiveness and safety in the broader, more heterogeneous populations seen in routine practice [1, 4]. Filling this evidence gap is crucial for equitable care, particularly for underrepresented groups such as adolescents, Black/African American patients, and those with comorbidities like chronic obstructive pulmonary disease (COPD) [5, 6]. A recent study now provides real-world data on tezepelumab, a biologic noted for its efficacy across a wide range of inflammatory biomarker levels, in just such a diverse patient group [7].
Study Design and Patient Cohort
To address the limited generalizability of prior trial data, investigators designed the PASSAGE study as a phase 4, post-marketing investigation. The multicenter, single-arm, open-label design, where both clinicians and patients knew the treatment administered, was chosen to evaluate the real-world effectiveness and safety of tezepelumab over 12 months in a diverse U.S. population with severe, uncontrolled asthma. The study deliberately sought to enroll patients often excluded from earlier trials, creating a cohort that more closely mirrors clinical practice.
The study included 286 participants aged 12 years and older. This cohort was intentionally heterogeneous, including patients with different asthma phenotypes, such as those with high (≥300 cells/µL) or low (<300 cells/µL) blood eosinophil counts, and those with or without allergies. Crucially, it also enrolled historically underrepresented populations, including Black/African American patients, adolescents, patients with comorbid mild-to-moderate COPD, and smokers with a history of ≥10 pack-years.
The primary outcome was the annualized asthma exacerbation rate (AAER). Researchers compared the rate during the 12 months before patients started tezepelumab (the baseline period) with the rate during the 12 months of treatment, allowing each participant to serve as their own control. The study protocol is registered at www.clinicaltrials.gov (NCT05329194).
Real-World Impact on Exacerbations and Lung Function
Treatment with tezepelumab resulted in substantial clinical benefits for this diverse patient population. For the primary outcome, the annualized asthma exacerbation rate (AAER) across all 286 participants decreased by 70% (95% CI: 63, 75), falling from a baseline of 2.88 to 0.87 during the treatment period. This robust effect was not limited to a specific subgroup; consistent reductions in AAER, ranging from 54% to 77%, were observed across all evaluated phenotypes and underrepresented populations, including those with low eosinophil counts or comorbid COPD.
Beyond reducing exacerbations, the therapy also improved pulmonary function. At week 52, the mean pre-bronchodilator forced expiratory volume in 1 second (FEV1) increased from baseline by 0.122 L (95% CI: 0.07, 0.17) for the overall cohort. The benefit was even more pronounced in the subgroup of patients with more significant baseline impairment (pre-bronchodilator FEV1 ≤ 80% of predicted), who saw their FEV1 increase by 0.212 L (95% CI: 0.15, 0.28). This degree of improvement in lung volume represents a tangible change in breathing capacity for patients with compromised respiratory function.
Improvements in Asthma Control and Quality of Life
Complementing the objective measures of exacerbations and lung function, the study also captured significant improvements in patient-reported outcomes that reflect the daily burden of severe asthma. Using several validated instruments, the researchers found that a majority of patients experienced meaningful benefits. Across the varied phenotypes and underrepresented populations, between 51% and 91% of participants reported clinically meaningful improvements at week 52 on the Asthma Control Questionnaire-6 (ACQ-6), a measure of symptoms and activity limitation.
Similar gains were seen on the Asthma Impairment and Risk Questionnaire (AIRQ), which assesses the condition's overall impact on daily life. Furthermore, health-related quality of life, measured by the comprehensive St George’s Respiratory Questionnaire (SGRQ), also showed clinically meaningful improvement in 51% to 91% of participants. This particular questionnaire evaluates symptoms, activity, and the psychosocial impact of respiratory disease, indicating that the benefits of tezepelumab extended beyond physical symptoms to patients' overall well-being.
Safety Profile in Real-World Use
A critical objective of this real-world study was to assess the safety of tezepelumab in a broad patient population, including those with characteristics that would have led to exclusion from earlier registration trials. After meticulous monitoring over the 12-month treatment period, the investigators reported that no new safety signals were identified. This finding is particularly reassuring for clinicians, as it held true across the entire diverse cohort.
The consistent safety profile in groups such as adolescents, Black/African American patients, individuals with comorbid mild-to-moderate COPD, and smokers provides valuable information for clinical decision-making. The absence of unexpected adverse events in these populations supports the use of tezepelumab in the complex patients frequently encountered in clinical practice, confirming that its safety profile remains stable outside the controlled environment of pivotal trials.
References
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2. Kyriakopoulos C, Gogali A, Markozannes G, Κostikas Κ. Biologic agents licensed for severe asthma: a systematic review and meta-analysis of randomised controlled trials. European Respiratory Review. 2024. doi:10.1183/16000617.0238-2023
3. Corren J, Menzies‐Gow A, Chupp G, et al. Efficacy of Tezepelumab in Severe, Uncontrolled Asthma: Pooled Analysis of the PATHWAY and NAVIGATOR Clinical Trials. American Journal of Respiratory and Critical Care Medicine. 2023. doi:10.1164/rccm.202210-2005oc
4. Menzies‐Gow A, Colice G, Griffiths JM, et al. NAVIGATOR: a phase 3 multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy and safety of tezepelumab in adults and adolescents with severe, uncontrolled asthma. Respiratory Research. 2020. doi:10.1186/s12931-020-01526-6
5. Korn S, Cook B, Simpson LJ, Llanos J, Ambrose CS. Efficacy of Biologics in Severe, Uncontrolled Asthma Stratified by Blood Eosinophil Count: A Systematic Review.. Advances in therapy. 2023. doi:10.1007/s12325-023-02514-0
6. Andō K, Fukuda Y, Tanaka A, Sagara H. Comparative Efficacy and Safety of Tezepelumab and Other Biologics in Patients with Inadequately Controlled Asthma According to Thresholds of Type 2 Inflammatory Biomarkers: A Systematic Review and Network Meta-Analysis. Cells. 2022. doi:10.3390/cells11050819
7. Niu M, Yabuta T, Makita N. [Mechanism of action of tezepelumab (TEZSPIRE®) and clinical trial results in asthma].. Nihon yakurigaku zasshi. Folia pharmacologica Japonica. 2024. doi:10.1254/fpj.23066