Antifibrotic Dose Reduction Not Tied to Faster IPF Progression

Standard-of-care therapies used to treat patients with idiopathic pulmonary fibrosis (IPF), although effective, are often poorly tolerated, leading researchers to investigate how dose reductions impact disease progression.¹

A study published in CHEST assessed how antifibrotic dose reduction and discontinuation of 2 IPF therapies, nintedanib (Ofev; Boehringer Ingelheim) and pirfenidone (Esbriet; Legacy Pharma), were associated with disease progression in patients with the condition.¹ Although both nintedanib and pirfenidone have been shown to slow lung function decline, specifically forced vital capacity (FVC)—a key measure of IPF progression—they’ve been associated with adverse events, sometimes severe. In a survey of 106 patients with IPF, approximately 90% said they experienced at least 1 adverse event as a result of antifibrotic treatment.² The risk of adverse events encourages the development of new IPF therapies that are more effective and better tolerated.

Why Real-World Antifibrotic Dosing Data in IPF Matter

Many dose reductions or discontinuations of antifibrotic therapies for IPF are likely due to adverse events, but the clinical implications of dose reduction have yet to be established. The real-world effect of the approved daily doses—2403 mg for pirfenidone and 300 mg for nintedanib—on slowing FVC decline has also yet to be established, as patients in routine clinical practice differ from those enrolled in clinical trials.¹

The retrospective cohort study included patients with IPF who were treated with either nintedanib or pirfenidone. Researchers pulled patient data from the Pulmonary Fibrosis Foundation Patient Registry (2016-2021) and the Duke University Health System’s electronic health records (EHRs) (2015-2021). Eligible individuals were aged 40 years or older with a pulmonary function test within 6 months of therapy initiation.¹

Patients were categorized by antifibrotic dosage: full dose, reduced dose, or stopped antifibrotic. Patients in the full dose group were defined as those who maintained the full antifibrotic dose with no stops lasting 3 months or more. Those in the reduced dose group remained on antifibrotic therapy but had at least 1 reduced-dose period lasting 3 months or more, and those in the stopped group were off antifibrotic therapy for 3 months or more. The primary outcome was IPF progression, a composite of a 10% or greater relative decline in percent predicted FVC (ppFVC), all-cause hospitalization, lung transplant, or death.¹

Disease Progression Remained Common Across Antifibrotic Dosing Groups

There were 545 patients included in the analysis from the registry and 1027 patients from Duke’s EHRs. Both cohorts were predominantly made up of White men with a median age of about 70 years.¹

The proportions of patients initiating pirfenidone and nintedanib were fairly evenly split in both cohorts. Over a median follow-up of 30 months in the registry and 14 months in the EHR cohort, 63.7% and 59.3% of patients, respectively, remained on the full antifibrotic dose. The proportions of patients in the reduced dose group (24.0% registry; 25.9% EHR) and the discontinued group (12.3% registry; 14.8% EHR) were comparable across cohorts.¹

A total of 455 and 574 patients in the registry and EHR cohorts, respectively, met the inclusion criteria for a 1-year landmark sensitivity analysis. At 1 year, 309 registry patients were maintained on the full dose, 104 were on a reduced dose, and 42 had discontinued. In the EHR cohort, 394 were maintained on the full dose, 160 were on a reduced dose, and 20 had discontinued.¹

The event rates for IPF progression per 100 person-years in patients on full dose, reduced dose, or antifibrotic discontinuation were 39.7, 46.6, and 70.7, respectively, in the registry and 44.8, 40.5, and 41.7 in the EHR cohort.¹

Compared with patients on full antifibrotic doses, patients who reduced or stopped therapy had a numerically increased risk of IPF progression in the registry, although the overall difference across dose groups was not statistically significant (adjusted HR, 1.17 [95% CI, 0.90-1.52] for dose reduction and 1.51 [95% CI, 1.04-2.18] for discontinuation; P = .073). In the EHR cohort, the adjusted HRs were 0.87 (95% CI, 0.69-1.09) for dose reduction and 0.94 (95% CI, 0.66-1.36) for discontinuation (P = .476). There were no significant overall differences in the individual components of the composite outcome by antifibrotic dose group in the registry.¹

The study had several limitations, including its retrospective design and potential confounding by indication, as patients whose doses were reduced or stopped may have differed in ways the data did not capture. Dosing was classified from pharmacy records and case report forms, dose resumptions, and therapy switches were not modeled, and the analysis may have been underpowered. The study was funded by Bristol Myers Squibb.¹

“We found that a substantial proportion of patients with IPF were treated with reduced doses or discontinued antifibrotic therapy, likely due to poor tolerability, and that disease progression remained common regardless of dosing strategy,” the study authors concluded. “These findings support the clinical acceptability of dose reduction strategies when required for tolerability, while underscoring the need for more effective and better-tolerated IPF therapies.”¹

References

1. Swaminathan AC, Stevens SR, Chopra P, et al. Association of antifibrotic dosing patterns with clinical outcomes in patients with idiopathic pulmonary fibrosis in real-world data sources. Chest. Published online September 29, 2026. doi:10.1016/j.chest.2026.09.029

2. McCrear S. FAQs on IPF therapies: current, emerging, and combination strategies. AJMC. March 20, 2026. Accessed October 28, 2026. https://www.ajmc.com/view/faqs-on-ipf-therapies-current-emerging-and-combination-strategies