Journal club

• Published in: Thorax Vol. 76; no. 12; p. 1266
• Main Author: Vijayakumar, Bavithra
• Format: Journal Article
• Language: English
• Published: BMJ Publishing Group Ltd and British Thoracic Society 15.11.2021
• Subjects: Journal club; not applicable
• ISSN: 0040-6376; 1468-3296
• DOI: 10.1136/thoraxjnl-2021-218369

Biological therapies targeting the type 2 (T2) inflammatory pathway have become incorporated into guidelines for the management of atopic asthma but have not consistently shown benefits in those patients with asthma without evidence of ongoing eosinophilic inflammation. Tezepelumab targets thymic stromal lymphopoietin which activates inflammation beyond the T2 pathway. Menzies-Gow et al (N Engl J Med, 2021, DOI: 10.1056/NEJMoa2034975) investigated the impact of tezepelumab on patients with asthma already established on medium-dose or high-dose inhaled corticosteroids and two exacerbations in the previous year in a phase 3, multicentre, randomised, double-blind, placebo-controlled trial. A total of 1061 patients underwent randomisation with 528 receiving tezepelumab and 531 placebo. Tezepelumab treatment reduced the annual exacerbation rate (0.93 compared with 2.10; rate ratio 0.44, 95% CI 0.37 to 0.53; p<0.001) with improvement also seen in subgroup analysis of patients with a low serum eosinophil count (<300 cells/µL). Furthermore, a significant improvement was seen in prebronchodilator FEV1 at week 52 compared with baseline (0.23 L tezepelumab, 0.09 placebo, p<0.001). Reduction in serum eosinophil counts and fraction of exhaled NO (FeNO) levels from baseline were documented as early as week 2 in the treatment arm and were sustained throughout the trial. Additionally, there were reductions in total serum IgE levels, indicating that tezepelumab targets multiple pathways to derive clinical benefit.