Efficacy and Safety of Nintedanib in Japanese Patients With Early-Stage Idiopathic Pulmonary Fibrosis: A One-Year Interim Analysis from a Multicenter Observational Study in Kyushu and Okinawa, Japan

Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease with a poor prognosis. Nintedanib, an antifibrotic agent, has been shown in clinical trials to slow the decline in forced vital capacity (FVC) and reduce acute exacerbations (AE-IPF). Long-term studies confirm its continued effectiveness, though side effects like diarrhea may affect adherence. Despite real-world data supporting nintedanib's benefits, no prospective study has assessed its efficacy in early-stage IPF. This study evaluated the efficacy, safety, and tolerability of nintedanib in patients with early-stage IPF to assess its effectiveness outside randomized control trials.

Methods: A 1-year interim analysis of a prospective, multicenter observational study was conducted in Kyushu and Okinawa, Japan. This study included 215 patients with early-stage IPF (stage I/II per the Japanese IPF severity system) who were followed up for 52 weeks. Changes in FVC and diffusion capacity of carbon monoxide (DLco); incidence of adverse events, acute exacerbations, and death; and factors associated with FVC decline and nintedanib discontinuation were evaluated.

Results: The percentage of predicted FVC (%FVC) remained stable, from 83.2% at baseline to 83.7% at 52 weeks, while %DLco decreased from 70.8% to 64.2%. Incidences of acute exacerbation and death were both 4.7%. Nintedanib was discontinued due to adverse events in 21.9% of the patients. Risk factors for FVC decline (>5%) included female sex, GAP stage II/III, low oxygen saturation (SpO₂) in the 6-minute walk test (6 MWT), and elevated biomarkers (KL-6). Significant factors for nintedanib discontinuation were advanced age, modified Medical Research Council (mMRC) grade I or higher, GAP stage II/III, low %FVC, low SpO₂ in the 6 MWT, short 6 MWT distance, and low albumin levels.

Conclusion: The findings of this interim analysis indicate that nintedanib has good efficacy, safety, and tolerability for early-stage IPF in real-world settings, outside randomized control trials.

Keywords: Antifibrotic agent; Early-stage; Efficacy; Idiopathic pulmonary fibrosis; Nintedanib; Safety.