Introduction: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease marked by a decline in forced vital capacity (FVC). While Nintedanib and Pirfenidone are standard treatments, the benefits of newer drugs like Nerandomilast and combination therapies remain unclear. This study employed a network meta-analysis (NMA) of randomized controlled trials (RCTs) to compare the effectiveness and safety of these treatments. Methods: Following PRISMA guidelines, a systematic review and Bayesian NMA were conducted. Databases were searched up to May 20, 2025, for RCTs involving adult patients with IPF treated with oral antifibrotic agents. The primary outcome was the change in FVC over one year; secondary outcomes included all-cause mortality and serious adverse events (SAEs). Results: Seven RCTs involving 4,206 patients were included. The greatest reduction in FVC decline was observed with high-dose Nerandomilast combined with Nintedanib (190 mL; 95% CI: 170–260), followed by low-dose Nerandomilast with Nintedanib (180 mL; 95% CI: 120–240), Nintedanib monotherapy (120 mL; 95% CI: 80–150), and high-dose Nerandomilast with Pirfenidone (110 mL; 95% CI: 39–180). These regimens significantly outperformed Pirfenidone and the combination of low-dose Nerandomilast with Pirfenidone. Most antifibrotic regimens, except NRD-LP, demonstrated superiority over placebo. No significant differences were observed among treatments in reducing all-cause mortality or in increasing the incidence of SAEs. Nintedanib showed the lowest risk of all-cause mortality, while high-dose Nerandomilast had the most favorable safety profile. Conclusion: This NMA confirms Nintedanib’s superior efficacy in IPF, with low-dose Nerandomilast emerging as a promising alternative. Combination therapies involving Nerandomilast showed limited additional benefit, highlighting the need for personalized treatment strategies and long-term data.
Tagam et al. (Sun,) studied this question.
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