Disproportionality Analysis of Hepatotoxic and Gastrointestinal Adverse Events Associated With Nintedanib Using the Japanese Adverse Drug Event Report (JADER) Database

Abstract

Background/aim: Nintedanib may cause adverse events such as elevated liver enzyme levels, diarrhea, and decreased appetite. These adverse events should be managed appropriately as they affect the quality of life of patients. This study has aimed to analyze patient characteristics and time-to-onset of adverse events caused by nintedanib using the Japanese Adverse Drug Event Report (JADER) database.

Patients and methods: Data from April 2004 to June 2023 were extracted from the JADER database and the patient characteristics of nintedanib administration were evaluated using reported odds ratio (ROR) and 95% confidence interval (95%CI). The data were analyzed for time-to-onset and patient characteristics such as age, sex, body mass index (BMI), and the presence or absence of prednisolone.

Results: The JADER database included 1,419 adverse event reports in which nintedanib was suspected. The number (%) and ROR of adverse events known to occur with the use of nintedanib were 72 (5.07%) cases of decreased appetite [ROR=7.09 (95%CI=5.59-8.99)], and 79 (5.57%) cases of diarrhea [ROR=6.52 (5.19-8.18)]. The median days until onset were 19.5 (IQR=6.25-50.5) days for hepatotoxicity, 119.5 (IQR=24.5-258.5) days for diarrhea, and 131.5 (IQR=20.5-334.5) days for decreased appetite.

Conclusion: Nintedanib is more likely to cause elevated liver enzyme levels, diarrhea, and decreased appetite than other drugs. These events occurred within approximately 3-4 months. The concomitant use of prednisolone may also be associated with gastrointestinal hemorrhage.

Keywords: Japanese Adverse Drug Event Report database; Nintedanib; adverse events; patient characteristics; real world evidence; time-to-onset.