Post-marketing safety surveillance of fostamatinib: an observational, pharmacovigilance study leveraging FAERS database

ABSTRACT

Objective

Fostamatinib, an FDA-approved oral small-molecule spleen tyrosine kinase (SYK) inhibitor, is used to treat thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) who have not responded to previous treatments. However, comprehensive safety data is lacking. This study uses the FDA Adverse Event Reporting System (FAERS) database to explore real-world adverse events (AEs) related to fostamatinib, aiming to inform its clinical use.

Methods

The FAERS database was retrospectively queried to extract reports associated with fostamatinib from 2019 to 2023. To identify and evaluate potential AEs in patients receiving fostamatinib, various disproportionality analyses such as 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) were employed.

Results

A total of 23 AE signals were included in our analysis. Among them, hypertension, blood pressure increase, blood pressure abnormality, hepatic enzyme increase, and diarrhea were consistent with the common AEs described for fostamatinib in clinical trials. In addition, unexpected serious AEs were detected including cerebral thrombosis and necrotizing soft tissue infection. The median time to onset of fostamatinib-related AEs was 86 days.

Conclusion

Our investigation revealed several possibly emergent safety concerns associated with fostamatinib in real-world clinical practice, which might provide essential vigilance evidence for clinicians and pharmacists to manage the safety issues of fostamatinib.

KEYWORDS:

• FAERS
• fostamatinib
• AE signals
• ITP
• disproportionality analysis
• pharmacovigilance

Disclaimer

As a service to authors and researchers we are providing this version of an accepted manuscript (AM). Copyediting, typesetting, and review of the resulting proofs will be undertaken on this manuscript before final publication of the Version of Record (VoR). During production and pre-press, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal relate to these versions also.

Abbreviations

FDA	=	Food and Drug Administration;
SYK	=	spleen tyrosine kinase
AEs	=	Adverse events;
FAERS	=	Food and Drug Administration Adverse Event Reporting System;
ROR	=	reporting odds ratio;
PRR	=	proportional reporting ratio;
BCPNN	=	Bayesian confidence propagation neural network;
MGPS	=	multi-item gamma Poisson shrinker;
ITP	=	Immune thrombocytopenia;
TPO-RA	=	thrombopoietin receptor agonists;
HBV	=	viral hepatitis type B;
wAIHA	=	warm antibody autoimmune hemolytic anemia;
MedDRA	=	Medical Dictionary for Regulatory Activities;
PT	=	Preferred term;
SOC	=	System organ class;
PS	=	primary suspected;
IC	=	information component;
VEGFR	=	vascular endothelial growth factor receptor;
CVD	=	cardiovascular disease;
ALT	=	alanine transaminase;
AST	=	aspartate transaminase;
CVT	=	cerebral venous thrombosis;
TEE	=	thromboembolic events;
NSTI	=	necrotising soft tissue infection

Declaration of interest

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.

Data availability statement

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

Author contributions

W Wei and JF Liu participated in the research design, the performance of the research, data analysis, and the writing of the paper. W Wei, E Chang, and YT Bai performed the data analysis. JF Liu managed and checked all the data. All authors read, checked, and approved the final manuscript.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14740338.2024.2387315

Additional information

Funding

This paper was not funded.