ArticleRespiratory research2024
Antifibrotics and mortality in idiopathic pulmonary fibrosis: external validity and avoidance of immortal time bias.
Article in Respiratory research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed.
- A systematic review of artificial intelligence-based diagnosis models for idiopathic pulmonary fibrosis.Journal of thoracic disease · 2026Review
- Efficacy and safety of nintedanib combined with pirfenidone versus monotherapy in patients with idiopathic pulmonary fibrosis: a systematic review and meta-analysis.American journal of translational research · 2026Review
- Emerging Concepts in Therapeutic Interventions for Idiopathic Pulmonary Fibrosis.Seminars in respiratory and critical care medicine · 2025Review
- Stratifying GAP Stages by MUC5B rs35705950 T-Allele Carriage Refines Survival Prediction in IPF.Lung · 2025Article
- Pathogenesis and current status of the treatment of lung cancer associated with idiopathic pulmonary fibrosis.Respiratory research · 2025Review
- Prognostic value of baseline serum KL-6 for mortality risk in patients with idiopathic pulmonary fibrosis receiving antifibrotic therapy: A retrospective cohort study.Therapeutic advances in respiratory diseaseArticle
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Authors and funding
12 authors.
Funding
Abstract
BACKGROUND AND
objectivePooled analyses of previous randomized controlled trials reported that antifibrotics improved survival in patients with idiopathic pulmonary fibrosis (IPF), but the results were only based on short-term outcome data from selected patients who met strict criteria. Observational studies/meta-analyses also suggested that antifibrotics improve survival, but these studies failed to control for immortal time bias that considerably exaggerates drug effects. Therefore, whether antifibrotics truly improve long-term survival in patients with IPF in the real world remains undetermined and requires external validity.
methodsWe used data from the Japanese National Claims Database to estimate the intention-to-treat effect of antifibrotics on mortality. To address immortal time bias, we employed models treating antifibrotic initiation as a time-dependent covariate and target trial emulation (TTE), both incorporating new-user designs for antifibrotics and treating lung transplantation as a competing event.
resultsOf 30,154 patients with IPF, 14,525 received antifibrotics. Multivariate Fine-Gray models with antifibrotic initiation as a time-dependent covariate revealed that compared with no treatment, nintedanib (adjusted hazard ratio [aHR], 0.85; 95% confidence interval [CI], 0.81-0.89) and pirfenidone (aHR, 0.89; 95% CI, 0.86-0.93) were associated with reduced mortality. The TTE model also replicated the associations of nintedanib (aHR, 0.69; 95% CI, 0.65-0.74) and pirfenidone (aHR, 0.81; 95% CI, 0.78-0.85) with reduced mortality. Subgroup analyses confirmed this association regardless of age, sex, and comorbidities, excluding certain subpopulations.
conclusionsThe results of this large-scale real-world analysis support the generalizability of the association between antifibrotics and improved survival in various IPF populations.
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