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

ABSTRACT

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.

KEYWORDS:

• Urinary tract infection
• Bruton tyrosine kinase inhibitor
• Food and Drug Administration Adverse Events Reporting System
• disproportionality analysis
• real-word analysis

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contribution statement

H. H. Yang was responsible for study conceptualization and design, data acquisition, data analysis and interpretation, manuscript preparation, manuscript editing; Z.X. Ding was responsible for data acquisition; Z.L. An were responsible for study conceptualization, design and interpretation.

Data availability statement

The datasets generated during and/or analyzed during the current study are available in the FAERS repository, https://www.fda.gov/drugs/questions-and-answers-fdas-adverse-event-reporting-system-faers/fda-adverse-event-reporting-system-faers-latest-quarterly-data-files

Additional information

Funding

This paper was not funded.