Suboptimal Dosing and Discontinuation of Antifibrotic Agents in Patients with Idiopathic Pulmonary Fibrosis (IPF)

OBJECTIVES: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal fibrotic lung disease. Antifibrotic agents have demonstrated ability to slow IPF progression, but many patients adjust dose due to dosing complexity or discontinue therapy to manage side effects. This study aims to evaluate suboptimal dosing and discontinuation of antifibrotic agents.

METHODS: This study used the Optum Research Database during October 2014 to December 2021 to identify adult (≥18 years of age) IPF patients with at least one claim for nintedanib or pirfenidone. The average daily dose was calculated each month during the 12-month post-index period. Suboptimal dosing was defined as daily dose not following prescribing information for at least 90 days, corresponding to daily dose less than 1602 mg (66.7% of full dose 2403 mg) for pirfenidone or less than 200 mg (66.7% of full dose 300mg) for nintedanib. Discontinuation was defined as gaps of ≥90 days in filling prescriptions. Nintedanib initiators were matched to pirfenidone initiators using nearest neighbor match. Semiparametric Cox PH model was used to assess time to suboptimal dosing and discontinuation.

RESULTS: 2,778 initiators (1389 each for nintedanib and pirfenidone) were included. After propensity score matching, there were no significant difference between the 2 groups. Mean age was 73.4 years in the nintedanib group with 61.5% male while mean age was 73.9 years and 60.5% male in the pirfenidone group. Eighty seven percent of patients in both groups were Medicare. The mean Charlson comorbidity index score was 2.1. The hazard ratio of suboptimal dosing for pirfenidone was 1.34 (95% CI 1.15 to 1.56) versus nintedanib. The hazard ratio for discontinuation of pirfenidone was 1.16 (95% CI 1.04 to 1.28) versus nintedanib.

CONCLUSIONS: Patients initiating pirfenidone had a higher risk of suboptimal dosing and greater likelihood of discontinuation as compared to those initiating nintedanib.