Safety of marketed biosimilar monoclonal antibody cancer treatments in the US: a disproportionality analysis using the food and drug administration adverse event reporting system (FAERS) database

ABSTRACT

Background

By 31 December 2022, the United States Food and Drug Administration (FDA) has approved 12 biosimilar monoclonal antibody cancer treatments. This study detected disproportionate adverse event (AE) reporting signals and compared safety profile of individual biosimilars to their originator biologics and between each pair of biosimilars.

Research design and methods

The FDA Adverse Event Reporting System data (6/1/2018–12/31/2022) were used to identify AE reports for rituximab, bevacizumab, trastuzumab, and their marketed biosimilars. Reporting odds ratios and empirical Bayesian geometric mean were computed to detect reporting disproportionality in serious, death, and specific AEs between studied biologics/biosimilars and all other drugs.

Results

Significant AE reporting signals were identified: 1) death for biological rituximab, pruritus for biosimilar rituximab-pvvr, and infusion-related reactions for biological rituximab and biosimilar rituximab-pvvr (significantly higher ROR for rituximab-pvvr than biological rituximab, p < .0001); 2) death for biological bevacizumab and biosimilar bevacizumab-bvzr (significantly higher ROR for bevacizumab-bvzr than biological bevacizumab, p < .0001), hypertension, platelet count decreased (PCD), and proteinuria for biological bevacizumab and biosimilar bevacizumab-awwb (significantly higher ROR of PCD for bevacizumab-awwb than originator bevacizumab, p = .001); and 3) rash for biosimilar trastuzumab-anns.

Conclusions

Findings call for large, longitudinal studies to examine causality of certain AEs with rituximab-pvvr and bevacizumab biosimilars.

KEYWORDS:

• Biological monoclonal antibody
• biosimilars
• bevacizumab
• trastuzumab
• rituximab
• adverse events
• disproportionality analysis
• pharmacovigilance

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 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 contributions

Both authors have substantially contributed to conceptualization of the study design, execution, acquisition of data, data analysis and interpretation, and writing and revising the article. Both authors agreed on the journal to which the article to be submitted. Both authors reviewed and agreed on all versions of the article before submission, during revision, the final version accepted for publication, and any significant changes introduced at the proofing stage. Both authors agree to take responsibility and be accountable for the contents of the article and to share responsibility to resolve any questions raised about the accuracy or integrity of the published work.

Data availability statement

The US FDA FAERS data supporting the results reported in the article can be accessed and downloaded from https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html.

Ethics approval

The study was granted exemption by the Auburn University Institutional Review Board, and the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14740338.2024.2348577.

Additional information

Funding

This paper was not funded.