Antifibrotics and mortality in idiopathic pulmonary fibrosis: external validity and avoidance of immortal time bias.
Respir Res
; 25(1): 293, 2024 Jul 31.
Article
in En
| MEDLINE
| ID: mdl-39085869
ABSTRACT
BACKGROUND AND OBJECTIVE:
Pooled 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.METHODS:
We 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.RESULTS:
Of 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.CONCLUSIONS:
The results of this large-scale real-world analysis support the generalizability of the association between antifibrotics and improved survival in various IPF populations.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Idiopathic Pulmonary Fibrosis
/
Antifibrotic Agents
Limits:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Country/Region as subject:
Asia
Language:
En
Journal:
Respir Res
Year:
2024
Document type:
Article
Affiliation country:
Japón