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Anti-thymic stromal lymphopoietin therapy reduced allergy-induced bronchoconstriction

Anti-thymic stromal lymphopoietin treatment in adults with allergic asthma reduced the fraction of exhaled nitric oxide and blood and sputum eosinophils, according to recent study results.

“While these data are very early, they help to confirm our belief that TSLP [thymic stromal lymphopoietin] is a critical early mediator that may be responsible for persisting airway inflammation and triggering the inflammatory response to allergens in allergic asthmatic patients,” Paul M. O’Byrne, MB, FRCPC, FRSC, executive director of the Firestone Institute for Respiratory Health, St. Joseph’s Healthcare, Hamilton, Ontario, said in a press release. “These results form the basis for further development of this compound.”

 

Paul M. O'Byrne

In the double blind study, Byrne and colleagues randomly assigned 31 nonsmoking adults with mild allergic asthma to receive three monthly doses of 700 mg AMG 157 (n=16) or placebo (n=15) in 1-hour intravenous infusion on days 1, 29 and 57. AMG 157 (Amgen) is a human monoclonal antibody that inhibits TSLP activity by binding to it.

Allergen challenges were conducted on days 42 and 84 to evaluate AMG 157’s effect in reducing the maximum percentage decrease in FEV1. Fraction of nitric oxide in exhaled air, blood and sputum eosinophils and airway hyperresponsiveness also were measured. Late asthmatic response at 3 to 7 hours after challenges was the primary endpoint.

Most measures of allergen-induced early or late asthmatic responses were reduced in severity by AMG 157.

“The maximum percentage decrease in the FEV1 during the late response was 34% smaller in the AMG 157 group than among placebo patients on day 42 (P=.09) and 45.9% smaller on day 84 (P=.02),” the researchers reported.

Levels of blood and sputum eosinophils significantly decreased in the AMG 157 cohort before and after the allergen challenge, as did the fraction of exhaled nitric oxide. The AMG 157-treated patients experienced 15 adverse events, compared with 12 in the placebo cohort; there were no deaths.

“These results support further work on mechanisms of action and investigation of the clinical benefit of AMG 157 in patients with poorly controlled asthma,” the researchers concluded.

Disclosure: See the study for a full list of relevant financial disclosures.