Abstract Background Brensocatib, a first-in-class oral, reversible dipeptidyl-peptidase-1 (DPP-1) inhibitor, received U.S. FDA approval on August 12, 2025 to treat adults with non-cystic fibrosis bronchiectasis. By preventing activation of neutrophil serine proteases, DPP-1 inhibition reduces airway inflammation. This meta-analysis evaluates the pooled efficacy and safety of DPP-1 inhibitors in bronchiectasis. Methods A systematic review of phase 2-3 randomized controlled trials comparing DPP-1 inhibitors with placebo was conducted using Stata 18.0 to assess exacerbation rates, adverse events, and risk of bias evaluated by RoB 2.0. Result Three randomized controlled trials (WILLOW 2020, ASPEN 2025, and SAVE-BE 2025) comprising 2,913 patients were included (1,485 active; 1,428 placebo). Pooled analysis showed a significant reduction in exacerbation frequency with DPP-1 inhibitors (RR 0.75; 95% CI 0.68-0.82; p 0.001), corresponding to an OR 0.71; 95% CI 0.63-0.81. Subgroup analysis demonstrated consistent benefit for brensocatib 10 mg (RR 0.77; 95% CI 0.67-0.89) and 25 mg (RR 0.80; 95% CI 0.69-0.93), with a greater magnitude for HSK31858 20-40 mg (RR 0.47; 95% CI 0.34-0.64). Adverse events were comparable between treatment and placebo (RR 1.06; 95% CI 0.92-1.23) with no increase in serious events. Overall, DPP-1 inhibition reduced bronchiectasis exacerbations by approximately 25% without compromising safety. Conclusion DPP-1 inhibition significantly reduces bronchiectasis exacerbations by approximately 25% without increasing adverse events, supporting it as a safe and effective anti-inflammatory therapy with very low risk of bias across included trials. This abstract is funded by: none
Aravazhi et al. (Fri,) studied this question.