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Background: Neutrophil elastase (NE) activity is increased in bronchiectasis and correlated with exacerbations. Brensocatib is an oral, selective, reversible dipeptidyl peptidase 1 inhibitor that blocks activation of neutrophil serine proteases and reduces NE activity. Aims: To evaluate the efficacy of brensocatib compared to placebo in subgroups of patients with bronchiectasis. Methods: WILLOW (NCT03218917) was a phase 2, randomized, double-blind, placebo-controlled study. Adults were randomized 1:1:1 to brensocatib 10 or 25 mg or placebo once daily. The primary endpoint was time to first bronchiectasis exacerbation over 24-weeks. Time to, and rate of, exacerbations were further analyzed in subgroups based on patient characteristics, medical history, disease severity, and baseline sputum NE. Safety and tolerability were assessed. Results: Brensocatib prolonged time to exacerbation vs placebo (brensocatib 10 mg, P=0.027; brensocatib 25 mg, P=0.044). Point estimates for time to, and rate of, exacerbation favored both brensocatib doses (hazard ratios Conclusions: Among patient subgroups (including analysis by baseline sputum NE, medical history, and disease severity), brensocatib consistently prolonged time to first exacerbation and reduced rates of exacerbation. |
