Differential Discontinuation Profiles between Pirfenidone and Nintedanib in Patients with Idiopathic Pulmonary Fibrosis.

Kazutaka Takehara,Toshitaka Maeno,Yuki Shin,Yasuyuki Saito,Yoshimasa Hachisu,Junichi Nakagawa,Yasuhiko Koga,Kazue Umetsu,Noriaki Sunaga,Takeshi Hisada,Mitsuyoshi Utsugi,Masakiyo Yatomi,Yuri Sawada,Seishi Yoshimi,Shunichi Kouno,Ikuo Wakamatsu

doi:10.3390/cells11010143

Abstract

Antifibrotic agents have been widely used in patients with idiopathic pulmonary fibrosis (IPF). Long-term continuation of antifibrotic therapy is required for IPF treatment to prevent disease progression. However, antifibrotic treatment has considerable adverse events, and the continuation of treatment is uncertain in many cases. Therefore, we examined and compared the continuity of treatment between pirfenidone and nintedanib in patients with IPF. We retrospectively enrolled 261 consecutive IPF patients who received antifibrotic treatment from six core facilities in Gunma Prefecture from 2009 to 2018. Among them, 77 patients were excluded if the antifibrotic agent was switched or if the observation period was less than a year. In this study, 134 patients treated with pirfenidone and 50 treated with nintedanib were analyzed. There was no significant difference in patient background, discontinuation rate of antifibrotic treatment over time, and survival rate between the two groups. However, the discontinuation rate due to adverse events within one year of antifibrotic treatment was significantly higher in the nintedanib group than in the pirfenidone group (76% vs. 37%, p < 0.001). Furthermore, the discontinuation rate due to adverse events in nintedanib was higher than that of pirfenidone treatment throughout the observation period (70.6% vs. 31.2%, p = 0.016). The pirfenidone group tended to be discontinued due to acute exacerbation or transfer to another facility. The results of this study suggest that better management of adverse events with nintedanib leads to more continuous treatment that prevents disease progression and acute exacerbations, thus improving prognosis in patients with IPF.

Highlights

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal lung disease of unknown etiology
A total of 77 patients were excluded for the following reasons: 49, because the observation period was less than one year and 28 because they were treated with pirfenidone and nintedanib in combination or had switched the drugs
Over the entire treatment period, the discontinuation rate due to adverse events was significantly higher in the nintedanib group than in the pirfenidone group (70.6 vs. 31.2%, p = 0.016)

Summary

Introduction

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal lung disease of unknown etiology. Environmental and occupational exposures have been suggested to play a role in the pathophysiology of IPF [1,2]. We reported inhaled silica/silicates in the lungs to be associated with the progression and prognosis in patients with IPF [3]. As an antifibrotic treatment for IPF in Japan, nintedanib became available in 2015, in addition to pirfenidone, which was available since 2008. Pirfenidone has been reported to be effective in treating familial IPF [4]. IPF has an average survival time of 3–5 years and the poorest prognosis among interstitial pneumonias [5]

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Discussion

Conclusion