Data mining and safety analysis of traditional immunosuppressive drugs: a pharmacovigilance investigation based on the FAERS database

ABSTRACT

Objective

The purpose of this study aimed to explore the new and serious adverse events(AEs) of Tacrolimus(FK506), cyclosporine(CsA), azathioprine(AZA), mycophenolate mofetil(MMF), cyclophosphamide(CTX) and methotrexate(MTX), which have not been concerned.

Methods

The FAERS data from January 2016 and December 2022 were selected for disproportionality analysis to discover the potential risks of traditional immunosuppressive drugs.

Results

Compared with CsA, FK506 has more frequent transplant rejection, and is more related to renal impairment, COVID-19, cytomegalovirus infection and aspergillus infection. However, CsA has a high infection-related fatality rate. In addition, we also found some serious and rare AE in other drugs which were rarely reported in previous studies. For example, AZA is closely related to hepatosplenic T-cell lymphoma with high fatality rate and MTX is strongly related to hypofibrinogenemia.

Conclusion

The AEs report on this study confirmed that the results were basically consistent with the previous studies, but there were also some important safety signals that were inconsistent with or not mentioned in previous published studies.

Expert opinion

The opinion section discusses some of the limitations and shortcomings, proposing the areas where more effort should be invested in order to improve the safety of immunosuppressive drugs.

KEYWORDS:

• Traditional immunosuppressive drugs
• FAERS
• data mining
• AE signals
• safety
• non-proportional 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

JJL and LC participated in research design, the performance of the research, data analysis, and in the writing of the paper. YZ, XQY, and FBH performed the data analysis. LW managed and checked all the data. All authors read, checked, and approved the final manuscript.

Data availability statement

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

Ethics statement

Patient consent was waived because the study is based on anonymous data that can be downloaded from a publicly available source.

Additional information

Funding

This work was supported by grants from the National Natural Science Foundation of China (82073921).