NAVIGATOR Trial Outcomes for Tezepelumab Use in Severe, Uncontrolled Asthma

In a broad population of patients with severe asthma, researchers found that use of tezepelumab resulted in higher proportions of patients with clinically meaningful improvements in patient-reported outcome measures for asthma control, symptoms, and health-related quality of life (HRQoL). Findings of this research were presented at the CHEST Annual Meeting, held virtually and in Orlando, FL, October 17 to 20.

Tezepelumab, a human monoclonal antibody, blocks the activity of thymic stromal lymphopoietin, an epithelial cell-derived cytokine associated with asthma pathogenesis.

In the multicenter, randomized, double-blind, placebo-controlled, phase 3 NAVIGATOR study (ClinicalTrials.gov Identifier: NCT03347279), tezepelumab significantly reduced exacerbations and improved lung function in patients with severe, uncontrolled asthma, including those with baseline blood eosinophil counts of less than 300 cells/mL.

In NAVIGATOR, patients (ranging from 12 to 80 years of age) with severe, uncontrolled asthma were randomized to receive tezepelumab 210mg or placebo subcutaneously every 4 weeks for 52 weeks. The current investigation reports findings derived from prespecified analyses of NAVIGATOR, evaluating patient-reported outcomes for asthma control, symptoms, and HRQoL.

After initiating treatment, patient-reported outcomes were assessed with the Asthma Control Questionnaire-6 (ACQ-6) monthly (starting at week 2), the standardized Asthma Quality of Life Questionnaire for patients aged 12 years and older (AQLQ[S]+12) every 3 months (starting at week 4), a weekly average of daily Asthma Symptom Diary (ASD) scores, and the St George’s Respiratory Questionnaire (SGRQ) every 6 months.

The investigators calculated the proportion of responders (defined by a score improvement from baseline of at least the minimum clinically important difference for each outcome measure).

A total of 1061 patients were randomized. Of those, 1059 patients received treatment (tezepelumab, n=528; placebo, n=531). For all patient-reported outcomes at week 52, the proportion of responders was higher in the tezepelumab group than in the placebo group. Results were as follows:

• ACQ-6: 86.2% vs 76.5%; odds ratio (95% confidence interval), 1.99 (1.43–2.76);
• AQLQ[S]+12; 77.5% vs 71.7%; 1.36 (1.02–1.82); ASD, 58.0% vs 50.1%, 1.68 (1.12–2.53);
• SGRQ: 81.7% vs 72.6%, 1.66 (1.17–2.36);
• ACQ-6 at week 2: 64.5% vs 56.4%, 1.48 (1.14–1.92);
• AQLQ[S]+12 at week 4: 63.8% vs 60.5%; 1.14 (0.88–1.48);
• ASD at week 1: 16.7% vs 11.0%; 1.82 (1.02–3.25); and
• SGRQ at week 24: 81.5% vs 70.7%; 1.79 (1.27–2.52).

“These results, together with previously reported improvements in exacerbations and lung function, demonstrate the benefit of tezepelumab in a broad population of patients with severe, uncontrolled asthma,” concluded the investigators.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Lugogo N, Ponnarambil S, Ambrose C, et al. Tezepelumab produces clinically meaningful responses on patient-reported outcome measures in patients with severe, uncontrolled asthma: results from the phase 3 NAVIGATOR study. Presented at: CHEST 2021; October 17-20, 2021; Orlando, FL/Virtual. Abstract 44A-47A.

This article originally appeared on Pulmonology Advisor