Time to Onset of Gemcitabine-induced Thrombotic Microangiopathy in a Japanese Population: A Case Series and Large-scale Pharmacovigilance Analysis

Abstract

Background/Aim: Gemcitabine-induced thrombotic microangiopathy (G-TMA) is associated with a high mortality rate. However, owing to its low incidence, data on G-TMA remain limited. Therefore, a detailed review of G-TMA cases is critical to understand this adverse event. In addition, reviewing literature and pharmacovigilance analytics may be useful to characterise G-TMA. Here, time to onset of G-TMA was analysed based on available data. Patients and Methods: We collected data for a case of TMA following gemcitabine administration at the Tokyo Metropolitan Geriatric Hospital. We also reviewed the literature on G-TMA cases in Japan from April 2000 to March 2022 to provide a case series. Moreover, we performed time-to-onset analysis of G-TMA using the data from the Japanese Adverse Drug Event Report (JADER) database. Results: Our case involved a patient with pancreatic cancer who developed thrombotic thrombocytopenic purpura 13 months after starting gemcitabine treatment. From the literature reviewed, in 14 out of 17 cases, G-TMA occurred 5-8 months after treatment initiation. The analysis of data from the JADER database showed that the median time to onset of G-TMA was 161 days. Weibull shape parameter analysis showed that the pattern of onset of G-TMA represented a random failure. Conclusion: This study elucidated the time to onset of G-TMA in a Japanese population. Weibull shape parameter analysis showed that G-TMA may not necessarily develop in a dose-dependent manner. These results may be useful for monitoring G-TMA in the clinical setting.

Hypoxia-inducible Factor Prolyl Hydroxylase Inhibitors and Hypothyroidism: An Analysis of the Japanese Pharmacovigilance Database

“…A WSP of <1 represents the early failure type, and the incidence decreases with time. A WSP of >1 represents the wear-out failure type, and the incidence increases with time (13). Furthermore, the influence of sex, age group, and clinical outcomes on the time to in vivo 38: 917-922 (2024) onset of hypothyroidism was evaluated using Kaplan-Meier method and Log-rank test.…”

“…Various analyses using pharmacovigilance databases were recently performed worldwide, and the results greatly contribute to the proper use of pharmaceuticals (13)(14)(15). In Japan, the Japanese Adverse Drug Event Report (JADER) database is maintained by the Pharmaceuticals and Medical Devices Agency (PMDA) and is open to anyone free of charge.…”