Urinary tract infection following the use of BTK inhibitors: a real-world analysis of post-marketing surveillance data.

BACKGROUND: Emerging case reports have raised awareness of urinary tract infection (UTI) which maybe a potentially serious complication. The present study aimed to summarize the clinical characteristics of patients with BTK inhibitor-related UTI, and the association between BTK inhibitors and UTI events was also assessed by disproportionality analysis. RESEARCH DESIGN AND METHODS: We conducted an observational, retrospective, and pharmacovigilance study using data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Data were retrieved from Quarter 1, 2004 to Quarter 2, 2022. The clinical characteristics of cases were summarized using descriptive statistics. We used the χ2 or Fisher exact methods for the analysis of categorical variables and the Mann-Whitney test or Student's t-text for the comparisons of continuous variables between fatal and non-fatal cases. A p-value less than 0.05 is considered to be statistically significant. Information component (IC) and reporting odds ratio (ROR) were used to evaluate the association. RESULTS: BTK inhibitors were identified as the suspected drug causing UTI in 539 cases. The age of those cases concentrated on 60-89 years (87.83%, data available in 263/539). UTI signals were detected during BTK inhibitors treatment (IC 0.95[0.83-1.08], ROR 1.96[1.80-2.13]). The association between BTK inhibitors and UTI events was shown among all groups but not in the group of age<60 years old. There were no significant differences in age and gender between fatal and non-fatal cases. However, a significant difference in reporting regions was found (p = 0.016), with the highest percentage of reported deaths occurring in Europe (26.15%, p = 0.000). CONCLUSIONS: Our study suggested a safety signal for UTI and BTK inhibitors compared to all other drugs in the database, especially in the elder (age ≥60). Further studies are needed to clarify these results.

A pharmacovigilance study of etoposide in the FDA adverse event reporting system (FAERS) database, what does the real world say?

Introduction: Etoposide is a broad-spectrum antitumor drug that has been extensively studied in clinical trials. However, limited information is available regarding its real-world adverse reactions. Therefore, this study aimed to assess and evaluate etoposide-related adverse events in a real-world setting by using data mining method on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: Through the analysis of 16,134,686 reports in the FAERS database, a total of 9,892 reports of etoposide-related adverse drug events (ADEs) were identified. To determine the significance of these ADEs, various disproportionality analysis algorithms were applied, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms. Results: As a result, 478 significant disproportionality preferred terms (PTs) that were identified by all four algorithms were retained. These PTs included commonly reported adverse events such as thrombocytopenia, leukopenia, anemia, stomatitis, and pneumonitis, which align with those documented in the drug's instructions and previous clinical trials. However, our analysis also uncovered unexpected and significant ADEs, including thrombotic microangiopathy, ototoxicity, second primary malignancy, nephropathy toxic, and ovarian failure. Furthermore, we examined the time-to-onset (TTO) of these ADEs using the Weibull distribution test and found that the median TTO for etoposide-associated ADEs was 10 days (interquartile range [IQR] 2-32 days). The majority of cases occurred within the first month (73.8%) after etoposide administration. Additionally, our analysis revealed specific high-risk signals for males, such as pneumonia and cardiac infarction, while females showed signals for drug resistance and ototoxicity. Discussion: These findings provide valuable insight into the occurrence of ADEs following etoposide initiation, which can potentially support clinical monitoring and risk identification efforts.