Efficacy of Antiinflammatory Therapies for Adults With Non-Cystic Fibrosis Bronchiectasis: A Systematic Review and Network Meta-Analysis.

Abstract

Non-cystic fibrosis bronchiectasis is characterized by chronic respiratory symptoms and radiologic airway dilatation. Sustained neutrophilic inflammation is a key driver, prompting interest in antiinflammatory pharmacotherapy as a new treatment paradigm; however, comparisons among antiinflammatory agents are lacking. What is the current profile concerning efficacy and safety of antiinflammatory therapies for bronchiectasis? We performed a systematic review and network meta-analysis of randomized controlled trials that evaluated inhaled or oral antiinflammatory agents in adults with CT scan-confirmed bronchiectasis. PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, International Clinical Trials Registry Platform, and ClinicalTrials.gov were searched. Trials enrolling adults and using ≥ 4 weeks of treatment were eligible. The primary outcome was the rate of overall and severe exacerbations; secondary outcomes were quality of life, 6-minute walk distance, FEV₁, and adverse events. The certainty of evidence was rated with Grading of Recommendations Assessment, Development, and Evaluation. Thirty-one trials (N = 4,092) evaluating 8 antiinflammatory agents were included. Compared with placebo, macrolides (rate ratio [RR], 0.44; 95% CI, 0.35-0.56) and dipeptidyl-peptidase-1 (DPP-1) inhibitors (RR, 0.73; 95% CI, 0.60-0.88) reduced overall exacerbation frequency (both moderate certainty). DPP-1 inhibitors reduced the frequency of severe exacerbations (RR, 0.70; 95% CI, 0.54-0.89; moderate certainty). Macrolides showed a similar downward trend of severe exacerbations with very serious imprecision (RR, 0.54; 95% CI, 0.19-1.54; low certainty). Adverse events and treatment discontinuation rates were trivial or small for all interventions. In subgroup analyses, DPP-1 inhibitors remained effective irrespective of baseline long-term macrolide use (with macrolide: RR, 0.77; 95% CI, 0.60-0.99; without macrolide: RR, 0.77; 95% CI, 0.67-0.89). Among individual macrolides, azithromycin showed the greatest reduction in exacerbation frequency (RR, 0.37; 95% CI, 0.29-0.48). These findings support the use of DPP-1 inhibitors and macrolide antibiotics as antiinflammatory treatment options for bronchiectasis with frequent exacerbations. PROSPERO; No.: CRD42024605694; URL: https://www.crd.york.ac.uk/prospero/.