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

Abstract

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 (D LCO /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.

The Difference Between SP-A and KL-6 Levels Responses for Treatment of Interstitial Lung Disease&nbsp;

“…On the other hand, our study indicated the changes in serum levels of SP-A and KL-6 correlated signi cantly with changes in respiratory function, which re ects disease activity. These results are also consistent with other reports [6,10,11,26,28,32,33,[35][36][37][38]. Because of the di culty of respiratory function tests for patients of ILD, this evidence strongly supports the value of biomarkers in monitoring the activity of ILDs.…”

Periostin: A Biomarker Useful in Treating Patients with Progressive Fibrosing Interstitial Lung Diseases

“…Possible PF-ILD patients would start to receive aggressive treatment including administration of anti-brotic agents immediately after their diagnosis and would continue with it. Although it is known that nintedanib and pirfenidone are tolerable, IPF patients receiving these drugs frequently show adverse effects such as gastrointestinal disorders and photosensitivity/rash; 10-20% of the patients discontinue the drugs [31][32][33][34]. Serum periostin, as a biomarker to predict short-term prognosis of lung function, would be useful in deciding whether to continue.…”

Pathological Roles and Clinical Usefulness of Periostin in Type 2 Inflammation and Pulmonary Fibrosis

“…It has been reported that the introduction of anti-fibrotic agents is effective in IPF treatment and that they have a certain inhibitory effect on fibrosis regardless of symptom severity [134]. In contrast, they are not recommended for all patients in terms of side effects [135,136]. Therefore, it is essential to properly evaluate the rate of progression of the disease when deciding on a treatment plan and providing guidance on daily life for patients with IPF.…”