Tezepelumab cuts asthma attacks in patients with severe asthma across seasons

Not only does tezepelumab reduce asthma symptomatic days, it prevents asthma exacerbations across all seasons in adolescents and adults with severe, uncontrolled asthma, according to the prespecified exploratory analyses of the NAVIGATOR trial presented at AAAAI 2022.

“We know that different seasons can impact asthma severity and control,” said lead author Dr Flavia Hoyte from National Jewish Health, Denver, Colorado, US, who alluded to the presence of different triggers of exacerbations such as allergens and viruses during different seasons. 

“This promising data confirms that tezepelumab is effective not only regardless of asthma phenotype, but also regardless of the season. For patients with uncontrolled, severe asthma, it is vital to have effective medications that can improve symptoms at all times of year,” she added. 

In the multicentre, double-blind, phase III trial, 1059 patients aged 12–80 years were randomized in a 1:1 ratio to receive subcutaneous injection of tezepelumab 210 mg or placebo every 4 weeks for 52 weeks.

Over 52 weeks, tezepelumab led to a greater reduction in the percentage of weekly asthma symptomatic days from baseline compared with placebo (median asthma symptomatic days, 42.0 vs 61.0 days per patient; mean change, 240.7 percent vs 232.8 percent; difference, 27.9 percent), as assessed using the Asthma Symptom Diary. [AAAAI 2022, abstract 046]

Importantly, the benefit was seen early during treatment and was sustained throughout the course of study (mean change, 217.9 percent vs 29.7 percent at week 2; and 238.3 percent vs 231.1 percent at week 26).

In another prespecified exploratory analysis, the researchers compared the annualized asthma exacerbation rate (AAER) between the two treatment groups by seasons. [AAAAI 2022, abstract 188]

 Reductions in the AAER were greater in the tezepelumab arm than the placebo arm across all seasons, with the greatest benefit seen during winter (reductions by 63 percent in winter, 46 percent in spring, 62 percent in summer, and 54 percent in autumn).

The tezepelumab arm experienced consistently fewer asthma exacerbations regardless of whether it was during winter (proportion of patients free from exacerbations, 81.7 percent vs 66.6 percent), spring (84.3 percent vs 76.3 percent), summer (86.8 percent vs 73.1 percent), or autumn (79.4 percent vs 66.6 percent).

“Tezepelumab, a human monoclonal antibody, blocks the actions of thymic stromal lymphopoietin [TSLP] and reduces downstream airway inflammation,” the researchers explained.

A separate analysis showed that tezepelumab significantly reduced inflammatory biomarkers such as FeNO levels by 30.6 percent, blood eosinophil count by 41.4 percent, IgE by 30.1 percent, IL-5 by 55.9 percent, and IL-13 by 45.7 percent compared with placebo at week 52. [AAAAI 2022, abstract 041]

“Tezepelumab treatment reduced airway and circulating inflammatory cytokines and biomarkers from as early as week 2 onwards,” said the researchers. Reductions for all biomarkers occurred since week 2, except IgE (reductions of which started at week 4).

“These reductions validate previous results and support the role of tezepelumab in reducing TSLP-mediated asthma inflammation,” the researchers stated.