Abstract Rationale Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease with poor prognosis and limited treatment options. The antifibrotic agents nintedanib and pirfenidone are currently approved for IPF management and have demonstrated efficacy in slowing disease progression. However, evidence directly comparing their survival outcomes and safety profiles remains inconclusive. This meta-analysis aimed to compare the efficacy and safety of nintedanib versus pirfenidone in patients with IPF. Methods A systematic review and meta-analysis were conducted following PRISMA guidelines. Comprehensive searches were performed in PubMed, Scopus, Web of Science, and Cochrane CENTRAL up to October 2025. Eligible studies included randomized controlled trials and comparative observational studies evaluating adults with IPF treated with nintedanib or pirfenidone. The primary outcome was survival (pooled hazard ratio HR). Secondary outcomes included all-cause mortality, treatment modifications, and adverse events. Random-effects models were used to calculate pooled estimates, and evidence certainty was assessed using the GRADE approach. The protocol was registered in PROSPERO (CRD420251184633). Results A total of 33 studies (2016-2025) including 7,400 IPF patients were analyzed. Most were retrospective or cohort-based with follow-up durations ranging from 12 months to over 5 years. Standard antifibrotic doses were consistently used (pirfenidone 2403 mg/day; nintedanib 300 mg/day). Nine studies assessing survival revealed no significant difference between nintedanib and pirfenidone (HR = 1.24; 95% CI: 0.91-1.69; p = 0.18; I² = 76.8%). Similarly, pooled data from 12 studies for all-cause mortality showed no significant difference (OR = 0.98; 95% CI: 0.73-1.31; p = 0.87; I² = 56.8%). Treatment modifications were common but statistically nonsignificant (OR = 1.37; 95% CI: 0.94-2.00; p = 0.11; I² = 84.7%), while dose reductions were significantly higher (OR = 2.27; 95% CI: 1.66-3.11; p = 0.0026). Adverse events were significantly more frequent with antifibrotic use overall (OR = 1.68; 95% CI: 1.27-2.21; p = 0.0003; I² = 49.4%). Conclusion This meta-analysis demonstrates that nintedanib and pirfenidone provide comparable survival and mortality outcomes in IPF patients. Both therapies are associated with frequent treatment adjustments and adverse events, emphasizing the importance of individualized therapy guided by tolerance and comorbidities. Future large-scale, head-to-head randomized trials are warranted to refine treatment strategies and improve long-term outcomes in IPF. This abstract is funded by: none
Hasson et al. (Fri,) studied this question.