Investigating bleeding adverse events associated with BTK inhibitors in the food and drug administration adverse event reporting system (FAERS)

ABSTRACT

Background

This study analyzed the bleeding adverse events (AEs) resulting from the treatment of B-cell lymphoma with Bruton tyrosine kinase (BTK) inhibitors, according to reports in the US Food and Drug Administration’s Adverse Event Reporting System (FAERS)

Methods

Bleeding AEs associated with BTK inhibitors (including ibrutinib, zanubrutinib, and acalabrutinib) from the first quarter of 2013 to the third quarter of 2023 were extracted. Reporting odds ratio (ROR) and proportional reporting ratio (PRR) were reported. Preferred Terms (PTs) of Medical Dictionary for Regulatory Activities (MedDRA) terms were mapped to System Organ Class terms (SOC) terms and analyzed bleeding AEs associated with three BTK inhibitors.

Results

A total of 463 cases of bleeding AEs were included. Contusion, subcutaneous hemorrhage, hematuria, and cerebral hemorrhage were included in PTs. Blood urine was present and subdural hematoma were also reported. The incidence of bleeding AEs was higher with ibrutinib (Case number = 10,696) than with zanubrutinib (Case number = 213) and acalabrutinib (Case number = 314).

Conclusion

Our findings indicate that bleeding AEs linked to BTK inhibitors in various conditions underscore the need for cautious clinical decision-making, particularly in nervous system disorders, injuries, poisoning, surgical complications, vascular disorders, and others.

KEYWORDS:

• BTK inhibitors
• B-cell malignancies
• adverse events
• bleeding
• FAERS

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 material discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or mending, or royalties.

Reviewer disclosures

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

Author contributions

Study concept and design: Xiaojun Zheng, Nan Shang, Xianlin Li. Acquisition of the data: Xianlin LI, Nan Shang. Analysis and interpretation of the data: Nan Shang, Xianlin Li, and Qianci Yan. Drafting the manuscript: Xiaojun Zheng, Nan Shang, Xianlin Li, Xiunan Yue, and Yang Liu. Statistical analysis: Nan Shang, Xianlin Li, Qianci Yan. Technical support:Nan Shang, Xianlin Li, Qianci Yan, and Xiaojun Zheng. All the authors read and approved the final manuscript.

Acknowledgments

We would like to thank Associate Chief Pharmacist Nan Shang from the Department of Clinical Pharmacy at the First Hospital of Shanxi Medical University for the guidance and funding support provided. We would like to thank Food and Drug Administration Adverse Event Reporting System.

Availability of data and material

The datasets for this study can be found in the https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14740338.2024.2339448

Additional information

Funding

This manuscript was funded by the Clinical Scientific Research Special Fund of the Wu Jieping Medical Foundation (grant numbers: 320.6750.2021-0813).