Real-world persistence with antifibrotic treatments: a nationwide study on claims data in France (The REPEAT study)

Long-term persistence with antifibrotic drugs is crucial to slow disease progression in fibrosing ILDs but is challenging due to adverse events. Large-scale, real-world studies investigating modifiable healthcare system factors associated with persistence are lacking.

The main objectives of this study were to assess the real-life persistence with antifibrotic treatments in the overall French population and to explore factors associated with patients' persistence with antifibrotic therapy.

In this retrospective observational study conducted using the French National Health Database System, all adults initiating nintedanib or pirfenidone between January 2019 and December 2021 were included. They were categorized by diagnosis (idiopathic pulmonary fibrosis, interstitial lung disease associated with systemic sclerosis, and progressive pulmonary fibrosis) using International Classification of Diseases 10th Revision codes. Persistence with antifibrotic therapy (defined as no treatment gap longer than 60 days), adherence to antifibrotic treatments, overall survival (OS), and event-free survival (EFS) were assessed. A multivariable Fine-Gray model identified factors associated with non-persistence.

Among 4,935 incident patients, the 12-month persistence rate with antifibrotic therapy was 70.8%. The median time of follow-up for incident patients was 27 months. The median time on antifibrotic therapy was 14.1 months. Switching between antifibrotics occurred in 16.6% of patients, mainly during the first year. At 12 months, OS and EFS were 85.8% and 57.4%, respectively, with lower rates observed among patients with IPF. Regular outpatient visits, follow-up in expert centers, and early supportive interventions (day-hospitalization, temporary treatment interruptions) were associated with increased persistence whereas suboptimal follow-up (< 2 pulmonary function tests during the follow-up period) was strongly associated with non-persistence (sHR = 3.1).

Structured patient follow-up and proactive management of adverse events, including treatment interruption, could be key to optimizing long-term persistence with antifibrotic therapy.