A retrospective study of the tolerability of nintedanib for severe idiopathic pulmonary fibrosis in the real world.

BACKGROUND: Nintedanib is a tyrosine kinase inhibitor that has been shown to suppress progression of idiopathic pulmonary fibrosis (IPF). The efficacy and tolerability of nintedanib for IPF has been previously proven in the INPULSIS® and INPULSIS-On® trials. The aim of our study was to clarify the tolerability of nintedanib in the real world for severe IPF patients who were unable to enter the INPULSIS® and INPULSIS-On® trials. METHODS: We retrospectively investigated medical records of 8 patients with severe IPF and 14 patients with non-severe IPF who had been treated with nintedanib. The criteria to define severe IPF were forced vital capacity (FVC) of <50% predicted and/or diffusing capacity of the lung for carbon monoxide/alveolar volume (DLCO/VA) of <30% predicted or unmeasurable. Severity of adverse event was evaluated using the Common terminology criteria for each adverse event version 4.0. We compared changes in FVC and serum KL-6 level, incidence and severity of adverse events, and incidence of permanent or temporary discontinuation of nintedanib in between severe and non-severe IPF groups. RESULTS: The median treatment period was 578.5 days. The most frequent adverse event was diarrhea (73%). Only 2 patients required permanent discontinuation of nintedanib due to adverse events. There was no difference in incidence or severity of adverse events or incidence of permanent or temporary discontinuation of nintedanib in between severe and non-severe IPF groups. Among subjects, decline in FVC during 6 months post-nintedanib treatment were significantly lower than prior to treatment, but change in serum KL-6 level showed no significant difference between these 2 timepoints. CONCLUSIONS: Our study showed that nintedanib was tolerable for IPF patients who would not have been eligible for entry into previous clinical trials due to low pulmonary function. Although therapeutic strategy for severe IPF should be planned carefully, initiation of nintedanib treatment should not be dismissed solely for reasons of low pulmonary function.