Many Patients With IPF Continue on Antifibrotics for 3 Years

Antifibrotic drugs pirfenidone and nintedanib, commonly prescribed for idiopathic pulmonary fibrosis (IPF) since 2014, have shown varied long-term results in a recent study published in Respiratory Research.¹

It was previously known that these medications were linked to improved rate of lung function decline, but less was understood about their long-term usage outside of clinical trials.

Most patients with newly diagnosed IPF continued using antifibrotics for at least 6 months | Image credit: fizkes – stock.adobe.com

To understand their real-world, long-term effects on transplant-free survival, respiratory hospitalization, and forced vital capacity, researchers turned to the Pulmonary Fibrosis Foundation Patient Registry (PFF-PR). The registry has been collecting data since 2016—shortly after the FDA approved pirfenidone and nintedanib—with a database of more than 2000 patients seeing physicians from the PFF Care Center Network, the largest collection of interstitial lung disease clinics in the US.

The study focused on patients who enrolled in the registry within a year of receiving an IPF diagnosis. Of the 389 patients in the registry eligible for the study, 288 (74%) had received antifibrotics for at least 180 days or 6 months, while 101 patients (26%) had no record of such treatment. Data from the PFF-PR also revealed that 63% of patients with newly diagnosed IPF continued using antifibrotics for at least 6 months, with a mean duration of antifibrotic use of 1113 days (range, 186-2106) or more than 3 years.

Patients who were treated with antifibrotics were significantly younger (69.8 vs 72.6 years, P = .008) and less likely to have smoked tobacco (61.1% vs 72.3% ever smokers, P = .04). According to the research authors, these findings were unsurprising.

“Both of these differences likely reflect hesitancy among providers to prescribe antifibrotics to older smokers, either due to fear of side effects or delay in prescription until other interventions, such as tobacco cessation or assessment and/or treatment for concomitant [chronic obstructive pulmonary disease], is complete,” they noted.

Between the 2 treatment groups, the authors saw no significant differences in race, gender, comorbidities, or baseline pulmonary function. However, the study population was almost entirely White (95.7%) and mostly male (80.5%). Most patients in the overall cohort (71.5%) did not have a family history of interstitial lung disease.

“Interestingly, patients on antifibrotic treatment had fewer symptoms at baseline compared to untreated patients,” the authors said. “While this difference reflects a pre-treatment imbalance between groups, it contrasts with findings from IPF-PRO demonstrating worse quality of life scores in patients being treated. As no clear relationship between antifibrotics and alleviation of symptom burden has been seen previously, this finding underscores that more study is needed regarding the relationship between symptom burden, antifibrotic use, and disease progression in IPF.”

The primary outcome of transplant-free survival was not significantly different between groups (adjusted HR [aHR], 0.799; 95% CI, 0.534-1.197, P = .28). While the time to respiratory hospitalization was significantly shorter for the patients receiving antifibrotics (aHR, 2.12; 95% CI, 1.05-4.30, P = .04), there was no significant difference in time to pulmonary function decline between treatment groups.

According to the authors, this multicenter study's strengths lie in its real-world patient enrollment, rigorous methodology to ensure continuous antifibrotic use, and extended follow-up period. However, limitations include potential biases inherent in smaller, retrospective studies and bias by indication, possibly leading to higher respiratory hospitalization rates in the treatment group. The study may also have lacked the statistical power to fully recognize a clinically significant effect on survival outcomes.

“Future studies should further investigate the role of antifibrotic therapy as it relates to patient-centered outcomes, such as respiratory hospitalization and quality of life, in addition to studying real-world outcomes of antifibrotics on progressive pulmonary fibrosis outside of the IPF paradigm,” the authors said.

While this study looked at both of the FDA-approved antifibrotics, past research presented at the American Thoracic Society 2019 Annual Meeting in Dallas compared their rates of long-term use.² Using Medicare data of patients with IPF aged 67 and older, researchers found higher adherence and persistence rates for pirfenidone compared with nintedanib. Specifically, discontinuation rates were higher for nintedanib (26.0%) compared with pirfenidone (19.5%), and fewer patients receiving nintedanib switched treatments.

References

1. Lee CT, Hao W, Burg CA, Best J, Kolenic GE, Strek ME. The impact of antifibrotic use on long-term clinical outcomes in the pulmonary fibrosis foundation registry. Respir Res. 2024;25(1):255. doi:10.1186/s12931-024-02883-2
2. DiGrande S. Real-world study finds high adherence, persistence with pirfenidone treatment in IPF. The American Journal of Managed Care^®. May 9, 2019. Accessed June 27, 2024. https://www.ajmc.com/view/realworld-study-finds-high-adherence-persistence-with-pirfenidone-treatment-in-ipf