Patients whose asthma remains uncontrolled despite treatment may benefit from a new monoclonal antibody that targets an inflammatory cytokine known to be promoted in asthmatic airways, according to data presented at the annual congress of the European Respiratory Society.
Writing in the Sept. 7 issue of the New England Journal of Medicine, researchers reported on a phase 2, randomized placebo-controlled trial of three dosing regimens of subcutaneous tezepelumab, which targets the epithelial cell–derived cytokine thymic stromal lymphopoietin (TSLP). The trial involved 584 patients with uncontrolled asthma, despite treatment with long-acting beta-agonists and medium to high doses of inhaled glucocorticoids.
MattZ90/thinkstockphotos
At 70 mg every 4 weeks, exacerbation rates were 61% lower than in the placebo group; at 210 mg every 4 weeks, they were 71% lower; and at 280 mg every 2 weeks, they were 66% lower (P was less than 001 in comparisons between each group and the placebo).
The overall annualized exacerbation rates by week 52 were 0.26 for the 70-mg group, 0.19 for the 210-mg group, and 0.22 for the 280-mg group, compared with 0.67 in the placebo group, regardless of a patient’s baseline eosinophil count. Patients treated with tezepelumab had a longer time to first asthma exacerbation. They also experienced a significantly higher change from baseline in their prebronchodilator forced expiratory volume in 1 second at week 52, when compared with patients on the placebo.
“The observed improvements in disease control in patients who received tezepelumab highlight the potential pathogenic role of TSLP across different asthma phenotypes,” reported Jonathan Corren, MD, of the University of California, Los Angeles, and his coauthors. “... Although TSLP is central to the regulation of type 2 immunity, many cell types that are activated by or respond to TSLP, such as mast cells, basophils, natural killer T cells, innate lymphoid cells, and neutrophils, may play a role in inflammation in asthma beyond type 2 inflammation.”
The incidences of adverse events and serious adverse events were similar across all groups in the study. Three serious adverse events – pneumonia and stroke in the same patient and one case of Guillain-Barré syndrome – in patients taking tezepelumab, were deemed to be related to the treatment.
The study was supported by tezepelumab manufacturers MedImmune (a member of the AstraZeneca group) and Amgen. Six of the seven authors are employees of MedImmune or Amgen. One author declared support and honoraria from several pharmaceutical companies, one declared a related patent, and five also had stock options in either MedImmune or Amgen.