In patients with severe, uncontrolled asthma, tezepelumab treatment resulted in clinically meaningful reductions in asthma exacerbations across patient subgroups defined by inflammatory biomarker levels and clinical characteristics. These were among the findings of a post hoc analysis of 2 clinical trials reported in the American Journal of Respiratory and Critical Care Medicine.
The analysis assessed tezepelumab efficacy and safety in subgroups of patients with severe, uncontrolled asthma defined by both clinical characteristics and inflammatory biomarker levels. Post hoc investigators used pooled data from the PATHWAY trial (ClinicalTrials.gov Identifier: NCT02054130) and NAVIGATOR trial (ClinicalTrials.gov Identifier: NCT03347279) to calculate the annualized asthma exacerbation rate (AAER) over 1 year and secondary outcomes in the overall pooled population and in specific subgroups.
The phase 2b PATHWAY and phase 3 NAVIGATOR trials were both multicenter, randomized, double-blind, placebo-controlled, parallel-group, 52-week studies with similar designs and eligibility criteria. The pooled analysis included 1334 patients: 275 patients from PATHWAY (from the tezepelumab 210 mg every 4 weeks and placebo groups only), and 1059 patients, including 82 adolescents, from NAVIGATOR. The pooled patient sample was then divided into the intervention group of 665 patients receiving tezepelumab (mean age, 50.5 years; 63.5% female) and the control group of 669 patients receiving placebo (mean age, 49.7 years; 64.4% female).
Overall, tezepelumab decreased the AAER during 52 weeks vs placebo by 60% (rate ratio [RR], 0.40; 95% CI, 0.34-0.48). Tezepelumab also lowered the AAER during 52 weeks compared with placebo in patients grouped according to baseline inflammatory biomarkers, with decreases ranging from 40% (RR, 0.60; 95% CI, 0.46, 0.79) in patients with fractional exhaled nitric oxide (FeNO) levels less than 25 ppb to 78% (RR, 0.22; 95% CI, 0.15, 0.33) in those who had a blood eosinophil count (BEC) of 450 cells/µL or more. Among patients with and without perennial aeroallergen sensitivity, tezepelumab reduced the AAER during 52 weeks compared with placebo by 62% (RR, 0.38; 95% CI, 0.30, 0.47) in those with perennial aeroallergen sensitivity and by 54% (RR, 0.46; 95% CI, 0.34, 0.62) in those without.
In addition to reductions in exacerbations in patients with high baseline BEC and FeNO levels, meaningful reductions were also observed in patients with low levels of T2 inflammatory biomarkers and across subgroups with varying perennial allergy status, maintenance OCS use, exacerbation history, ICS dose, history of nasal polyps, and BMI.
Analysis of multiple subgroups defined by biomarkers related to BEC and perennial allergy status showed that the AAER over 52 weeks was consistently lower with tezepelumab vs placebo, with decreases ranging from 38% in patients with a BEC of less than 300 cells/µL and without perennial allergy to 71% in those with a BEC of 300 cells/µL or more and with perennial allergy.
Reductions in exacerbations were also seen in patients with low levels of T2 inflammatory biomarkers and across subgroups with varying exacerbation history, nasal polyps history, body mass index, maintenance oral corticosteroid use, and inhaled corticosteroid dose.
Overall, tezepelumab was associated with a 79% decrease in AAERs associated with hospitalizations or emergency department visits over 52 weeks vs placebo. With respect to other outcomes, tezepelumab also improved lung function, asthma control, and HRQoL compared with placebo.
In assessing adverse events (AEs), investigators found the proportion of patients reporting an on-treatment AE was 75% in the tezepelumab group and 77% in the placebo group. An on-treatment serious AE occurred in 9% and 13% of patients in the tezepelumab and placebo groups, respectively.
In citing study limitations, the investigators noted that there were some differences in eligibility criteria between the studies, including a small cohort of adolescents in NAVIGATOR but not in PATHWAY, as well as slightly different requirements relating to pre-study inhaled corticosteroid dosing and the number of exacerbations within the previous 12 months. Also, the large number of recruitment sites may be a potential limitation given the wide variability of resources and practice patterns in severe asthma treatment.
“Together, these findings further support the benefits of tezepelumab in a broad population of patients with severe, uncontrolled asthma,” noted the researchers. “In addition to reductions in exacerbations in patients with high baseline BEC and FeNO levels, meaningful reductions were also observed in patients with low levels of T2 inflammatory biomarkers and across subgroups with varying perennial allergy status, maintenance OCS use, exacerbation history, ICS dose, history of nasal polyps, and BMI.”
Disclosure: This study was funded by AstraZeneca and Amgen Inc. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.