Antifibrotic therapy can extend survival in patients with
The new findings highlight the heterogeneity of PPF and the need for a nuanced, multidisciplinary approach to care, according to the investigators. The study was published in
Antifibrotic drugs like pirfenidone (Esbriet; Genentech) and nintedanib (Ofev; Boehringer Ingelheim) have been shown to be effective in patients with idiopathic pulmonary fibrosis (IPF) and in
Patients with PPF have a particularly poor prognosis, they said. Yet, there are different theories about how best to define PPF with regard to the need for antifibrotic therapy.1 One proposal is to use the criteria of PPF “despite management” to refer to patients who experience progression despite receiving standard non-antifibrotic therapy. Such a designation has already been used in a major clinical trial. The authors hypothesized that using the subcategory of PPF might make it possible to better discriminate between patients who will and will not benefit from antibiotic therapy.
The authors retrospectively analyzed 327 patients with PF-ILD (134 antifibrotics, 193 non-antifibrotics), 567 patients with PPF (149 antifibrotics, 418 non-antifibrotics), and 326 patients with PFF despite management (115 antifibrotics, 211 non-antifibrotics). All of the patients were at least 18 years of age, and all had been diagnosed with chronic ILD between 2012 and 2023. The authors used the parametric G formula, the time-varying Cox hazard model, and inverse probability weighting to analyze whether antifibrotic therapy was associated with increased survival.
The analysis was based on 2 counterfactuals: a scenario in which all patients had been treated with antifibrotic therapy and a scenario in which none had received antifibrotic therapy. The analysis showed that antifibrotic therapy led to statistically significant improvements in estimated survival for the first 3 years in patients with PF-ILD. In the case of the PPF cohort, though, no clear survival benefit was identified until “despite management” status was taken into consideration. When the analysis was limited to patients with PPF despite management, the survival benefit returned and was consistent across all 4 years.
The authors said their findings highlight the nuances of pulmonary fibrosis diagnosis and the implications of those nuances for therapeutic decisions.
“Our analysis suggested that the key distinction between PPF and PF-ILD diagnoses might hinge on the presence or absence of the ‘despite management’ criterion and underscores that the diagnostic criteria for PF-ILF and PFF ‘despite management’ were more stringent in identifying patients who would benefit from antifibrotic drugs,” the authors said. Prescribing antifibrotic drugs on a “free-for-all” basis to anyone with PPF is unwise, they noted.
Their data also show the importance of a multidisciplinary approach to diagnosis. They said using a criterion of “despite management” that has been determined by a multidisciplinary discussion may prove to be a more robust, accurate predictor of treatment response.
The investigators said their work was subject to certain limitations, including the real-world design and the lack of rigid pre-specified criteria to label patients as PFF “despite management.” They added that their study also did not consider discontinuation of antifibrotic treatment.
The authors concluded further investigation and validation are warranted, but that their data show that the designation of “despite management” could play a critical role in patient care decisions.
References:
- Niitsu T, Fukushima K, Komukai S, et al. Effectiveness of antifibrotic treatment in real-world patients with progressive pulmonary fibrosis. Respir Med. Published online September 9, 2025. doi:10.1016/j.rmed.2025.108347
- Flaherty KR, Wells AU, Cottin V, et al. Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med. 2019;381(18):1718-1727. doi:10.1056/NEJMoa1908681.