Tezepelumab, the novel thymic stromal lymphopoietin inhibitor, reduced the rate of annual disease exacerbations in patients with severe, uncontrolled asthma regardless of the number of additional controller medications they were taking--by as much as 68% in patients taking 2 added medications.
The findings, from a post-hoc analysis of the phase 3 52-week NAVIGATOR study, were presented at the American College of Chest Physicians (CHEST) 2022 Annual Meeting, October 16-19, 2022.
In the multicenter randomized placebo-controlled NAVIGATOR trial, tezepelumab significantly reduced annualized asthma exacerbation rates (AAER) and improved prebronchodilator (pre-BD) FEV1 in patients prescribed medium- or high-dose inhaled corticosteroids (ICS) and ≥1 additional controller medication, with or without oral corticosteroids. There were 1059 participants in the original NAVIGATOR trial, aged 12 to 80 years; approximately half received tezepelumab 210 mg and half were administered placebo.
In this post-hoc analysis of the trial, investigators assessed AAER and change in pre-BD FEV1 by subgroups of NAVIGATOR participants receiving 1 (n=493), 2 (n=381), or ≥3 (185) additional controller medications at baseline. The most common additional medications used among all participants were long-acting β-agonists, according to the study abstract.
During the 12 months before initiation of the NAVIGATOR trial, a greater proportion of study participants receiving at least 3 additional asthma controller medications (60%) experienced more than 2 exacerbations vs those who received either 2 (41%) or 1 (32%) additional controllers.
During the course of the 52 weeks, the post-hoc analysis investigators report, the AAER for participants receiving placebo in the additional controller groups was 1.4 (95% CI, 1.1–1.7) for 1 additional medication; 2.5 (95% CI: 2.1–3.1) for 2 additional agents; and 3.3 (95% CI: 2.5–4.5) for ≥3 additional controllers
Compared with placebo, tezepelumab over the study period significantly reduced the AAER in all 3 added controller subgroups as follows:
Further analysis found that tezepelumab also improved pre-BD FEV1 versus placebo across all subgroups (least-squares mean difference: 0.10 L [95% CI, 0.03–0.18], 0.13 L [95% CI, 0.05–0.22] and 0.22 L [95% CI, 0.10–0.34], respectively).
Commenting on clinical implications of their findings the investigators write: “This analysis demonstrates the efficacy of tezepelumab in a broad population of patients with severe, uncontrolled asthma, including those receiving multiple additional asthma controller medications.”
Reference Kraft M, Colice GL, Ambrose C, et al. Efficacy of tezepelumab in patients with severe, uncontrolled asthma grouped by number of additional asthma controller medications: results from the phase 3 NAVIGATOR study. Abstract presented at: CHEST 2022 Annual Meeting; October 16-19, 2022; Nashville, TN.