Journal article
Exacerbation risk in patients with bronchiectasis receiving DPP-1 inhibitors vs placebo: A meta-analysis of RCTs
Respiratory medicine, v 251, p108607
22 Dec 2025
PMID: 41443427
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
No therapies have been approved to alter bronchiectasis progression. Dipeptidyl peptidase-1 (DPP-1) inhibitors, which target neutrophil serine protease activation, are under investigation as potential disease-modifying agents.
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing DPP-1 inhibitors versus placebo in patients with non-cystic fibrosis bronchiectasis. PubMed, Cochrane, EMBASE, Web of Science, Scopus, ClinicalTrials.gov, and ICTRP were searched from inception until April 26, 2025. Primary outcomes included time to first exacerbation and proportion of patients remaining exacerbation-free. Secondary outcomes included post-bronchodilator % Forced Expiratory Volume in 1 s (FEV1), Quality of Life-Bronchiectasis (QoL-B) questionnaire scores, and rate of adverse events. Time-to-event outcome was analyzed using Kaplan-Meier (KM)-estimated individual patient data (IPD), whereas random-effects meta-analyses were performed for remaining outcomes.
2523 patients from four RCTs were included, of whom 1689 (66.9 %) received DPP-1 inhibitors. Compared with placebo, DPP-1 inhibitors prolonged the time to first exacerbation (HR 0.79; 95 % CI: 0.71 to 0.88) and increased the proportion of patients remaining exacerbation-free (RR 1.33; 95 % CI 1.12 to 1.58). A slower decline in post-bronchodilator % FEV1 was observed (MD 1.1 %; 95 % CI 0.05 to 2.15), but no difference in QoL-B scores (MD 1.35; 95 % CI -0.72 to 3.42). The safety profile of DPP-1 inhibitors was acceptable and comparable to placebo. Moderate certainty was found across endpoints.
DPP-1 inhibitors prolong time to first exacerbation and reduce exacerbation rates in patients with bronchiectasis, with an acceptable safety profile. These findings support their potential as a disease-modifying strategy.
PROSPERO (CRD420251042542).
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•DPP-1 inhibitors reduce exacerbation risk in patients with bronchiectasis.•May represent the first disease-modifying therapy for bronchiectasis.•May slow lung function decline, with no observed impact on quality of life.•Well-tolerated, with a safety profile comparable to placebo.
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Details
- Title
- Exacerbation risk in patients with bronchiectasis receiving DPP-1 inhibitors vs placebo: A meta-analysis of RCTs
- Creators
- Giulia Carvalhal - Universidade Federal de Campina GrandeJúlia Moreira Diniz - Universidade Federal de Minas GeraisLarissa Calixto Hespanhol - Universidade Federal de Campina GrandeDavid Curi Barbosa Izoton Cabral - Universidade de São PauloJafar Aljazeeri - Military Hospital
- Publication Details
- Respiratory medicine, v 251, p108607
- Publisher
- Elsevier Ltd; LONDON
- Number of pages
- 8
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pulmonary, Critical Care, and Sleep (Medicine)
- Web of Science ID
- WOS:001654719600001
- Scopus ID
- 2-s2.0-105026629339
- Other Identifier
- 991022148105704721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Cardiac & Cardiovascular Systems
- Respiratory System