Real-World Safety and Tolerability of Nintedanib in Patients with Idiopathic Pulmonary Fibrosis: Interim Report of a Post-Marketing Surveillance in Japan

INTRODUCTION: Nintedanib is recommended for the treatment of idiopathic pulmonary fibrosis (IPF); however, treatment discontinuation due to adverse events (AEs) is common. A large-scale post-marketing surveillance study is investigating the real-world tolerability/safety of nintedanib in Japanese patients with IPF in routine clinical practice. Here, we report a 12-month interim analysis of this study. METHODS: The study included Japanese patients with IPF who started nintedanib between 31 August 2015 and 25 December 2018. The primary outcome was the frequency of adverse drug reactions (ADRs), defined as AEs for which a causal relationship with nintedanib could not be excluded. The secondary outcome was change from baseline in forced vital capacity (FVC). Outcomes were analysed in patients who stopped ('discontinued' subgroup) and continued ('continued' subgroup) nintedanib after 12 months. A multivariate analysis was performed to determine potential risk factors for treatment discontinuation. RESULTS: Of 5578 patients in the safety analysis set, 2795 (50.1%) discontinued nintedanib within 12 months of treatment initiation. Overall, 3767 patients (67.5%) had ADRs, with 1356 (24.3%) discontinuing nintedanib because of an ADR. Among patients in the 'discontinued' subgroup (n = 2795), 1442 (51.6%) discontinued because of an ADR. The most common ADRs causing discontinuation within 3 and 12 months were hepatic function abnormal (n = 137/730; 18.8%) and diarrhoea (n = 190/1442; 13.2%), respectively. At 12 months, the decrease in FVC from baseline was smaller in the 'continued' versus the 'discontinued' subgroup (adjusted mean ± standard error change - 104.4 ± 10.9 ml vs. - 311.2 ± 29.2 ml). Stage III/IV IPF and FVC < 70% predicted at baseline were risk factors for early treatment discontinuation. CONCLUSION: About 50% of Japanese patients with IPF discontinued nintedanib within the first year of treatment, with worse lung function being associated with an increased risk of early treatment discontinuation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02607722; European Union electronic register of Post-Authorisation Studies: EUPAS10891.