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. 2025 Aug 15.
doi: 10.1007/s00417-025-06895-6. Online ahead of print.

An assessment of anti-VEGF drugs safety based on real-world data: from popularity to spontaneous reporting in eudravigilance database

Chen Li  1 , Mingxuan Chen  2 , Yicheng Lu  3
Affiliations

An assessment of anti-VEGF drugs safety based on real-world data: from popularity to spontaneous reporting in eudravigilance database

Chen Li et al. Graefes Arch Clin Exp Ophthalmol. .

Abstract

Purpose: Anti-vascular endothelial growth factor (VEGF) drugs are the first-line treatment for neovascular age-related macular degeneration (nAMD). This study analyzed four commonly used anti-VEGF drugs, preliminarily compared the search query results for these drugs on Google to assess public interest and analyzed the profile of ocular adverse drug reactions (ADRs) for these drugs in the EudraVigilance (EV) database.

Methods: A descriptive retrospective study was conducted. We observed four commonly used anti-VEGF drugs for the clinical treatment of nAMD, with ADR reports sourced from the EV database. Data collected included age, gender, regional distribution, and report origins. We analyzed the overall characteristics of these ADR reports and explored the distribution across 27 System Organ Classes (SOCs) for these drugs. Additionally, we compared the off-label use ratios and severe outcomes of these drugs. Subsequently, we used disproportionality analysis (DPA) to compare the relationship between these drugs and ocular ADRs. Lastly, we compared the most common ocular ADRs among different drugs and the similarities and differences in ocular ADRs.

Results: Google Trends indicated that in 2024, the interest scores for the four drugs ranked from highest to lowest were aflibercept, ranibizumab, faricimab, and brolucizumab. As of October 22, 2024, the total number of Individual Case Safety Reports (ICSRs) for the four drugs uploaded in EV was 32,878, with a higher proportion of ADR reported in brolucizumab-treated cases compared to the other three drugs. The age group of 65-85 years reported the highest incidence, and a higher proportion of ADRs occurred in females. Compared to the European Economic Area (EEA), more cases were reported for these drugs in NON-EEA regions, with reports primarily from healthcare professional (HP). Eye disorders were the most frequently reported among the four drugs. The frequency of ADRs reported for off-label use was highest with faricimab, while ranibizumab had a higher number of cases with severe outcomes. DPA revealed that brolucizumab had a significantly higher reporting rate of ocular ADRs compared to the other three inhibitors.

Conclusion: Anti-VEGF drugs often cause ocular ADRs when treating nAMD, which should be a clinical concern. To reduce the risk of adverse reactions, clinicians should closely monitor patients using these drugs.

Keywords: Adverse drug reaction; EudraVigilance; Pharmacovigilance; Spontaneous reporting; Vascular endothelial growth factor; Vascular endothelial growth factor inhibitor.

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Conflict of interest statement

Declarations. The authors declare that this study complies with all relevant ethical standards for research involving human data. All data analyzed were obtained from publicly available databases (Google Trends and EV) and did not involve direct human subject participation, thus not requiring institutional review board approval. No conflicts of interest, financial or otherwise, influenced the design, execution, or reporting of this research. No funding was received for this work. Ethical approval: This article does not contain any studies with animals performed by any of the authors. Informed consent: Informed consent was obtained from all individual participants included in the study. Conflict of interest: All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

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