Tezepelumab Effectively Reduces Asthma Exacerbations in Patients Across BMI Ranges

A post hoc analysis was conducted on the phase 3 NAVIGATOR study and the DESTINATION extension study. The analysis revealed that tezepelumab, a human monoclonal antibody targeting thymic stromal lymphopoietin (TSLP), effectively reduces asthma exacerbations. This reduction occurred over a 2-year period. Remarkably, tezepelumab's efficacy was consistent regardless of the patient's baseline body mass index (BMI). This study was published in CHEST Journal by Chupp G. and colleagues.

Obesity has been linked to an increased risk of asthma incidence and severity. This post hoc analysis focused on the efficacy of tezepelumab in patients with severe, uncontrolled asthma, considering their baseline BMI. Tezepelumab is a monoclonal antibody designed to block the effects of TSLP, a key cytokine involved in asthma pathogenesis. The study involved patients with severe, uncontrolled asthma, and the results demonstrated consistent efficacy in improving asthma control and reducing exacerbations, making it a promising treatment option for a broad population of patients with varying BMIs.

The study combined data from NAVIGATOR, a phase 3 study, and the DESTINATION extension study. NAVIGATOR included patients with severe, uncontrolled asthma aged 12-80, while DESTINATION was a double-blind, placebo-controlled extension study involving patients who were initially part of NAVIGATOR. Patients in NAVIGATOR who were randomized to receive tezepelumab continued their treatment, while those who initially received a placebo were re-randomized to either tezepelumab or a placebo. This analysis assessed the annualized asthma exacerbation rate (AAER) over 104 weeks, grouping patients by their baseline BMI: healthy, overweight, or obese. Additionally, weight changes were evaluated in patients receiving tezepelumab in both studies.

• In the placebo group (n=531), patients with higher BMIs had higher AAERs over 104 weeks.
  
• Tezepelumab (n=528) reduced the AAER over 104 weeks by 58%, 59%, and 57% in patients across BMI ranges (< 25 kg/m², 25 to < 30 kg/m², and ≥ 30 kg/m², respectively).
• In patients who received tezepelumab only (n=389) or placebo only (n=197) in both studies, increases in BMI were modest, demonstrating that tezepelumab did not significantly impact patients' weight.

The analysis shows that tezepelumab effectively reduces asthma exacerbations over a two-year period, regardless of a patient's baseline BMI. This finding underscores the drug's potential to provide consistent benefits in improving asthma control and reducing exacerbations in patients with varying BMIs, making it a valuable therapeutic option for a broad population of individuals with severe, uncontrolled asthma.

Reference:

Chupp, G. L., Lugogo, N. L., Wechsler, M. E., Lawson, K., Lindsley, A., Spahn, J. D., & Ambrose, C. Long-term efficacy of tezepelumab in patients with severe, uncontrolled asthma by baseline body mass index. Chest,2023;164(4):A9–A14. https://doi.org/10.1016/j.chest.2023.07.075