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Overview of the Safety of Anti-VEGF Drugs: Analysis of the Italian Spontaneous Reporting System

Drug Safety volume 40, pages 1131–1140 (2017)Cite this article

Abstract

Introduction

Anti-vascular endothelial growth factor (anti-VEGF) drugs are widely used for the treatment of several cancers and retinal diseases. The systemic use of anti-VEGF drugs has been associated with an increased risk of serious adverse reactions. Whether this risk is also related to intravitreal administration of anti-VEGF drugs is unclear.

Objective

The aim of this study was to provide an overview of the safety of anti-VEGF drugs in oncology and ophthalmology settings using the Italian Spontaneous Reporting System (SRS).

Methods

We selected all suspected adverse drug reaction (ADR) reports attributed to anti-VEGF drugs and conducted descriptive frequency analyses stratified by indication of use. As a measure of disproportionality, we calculated the proportional reporting ratio with 95% confidence intervals at the level of standardized Medical Dictionary for Regulatory Activities (MedDRA®) queries (SMQs).

Results

Of a total of 2472 anti-VEGF drug-related reports, 2173 (87.9%) and 299 (12.1%) were attributed to systemic and intravitreal use of these drugs, respectively. The frequency of serious ADRs reported was higher for intravitreal administration of anti-VEGF drugs than for systemic use in patients with cancer (58.9 vs. 34.1%) (p < 0.001) and were disproportionally associated with ischemic heart disease and thromboembolic and cerebrovascular events. Most serious ADRs related to anti-VEGF drugs in patients with cancer are known and clinically relevant (e.g., gastrointestinal and vascular disorders).

Conclusions

This study documented that serious ADRs and systemic toxicity may occur not only with systemic use of anti-VEGF drugs in patients with cancer but also with intravitreal administration. Close monitoring of cardio/cerebrovascular adverse events should be considered during treatment with all anti-VEGF drugs.

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Author information

Affiliations

  1. Sicilian Regional Pharmacovigilance Center, Messina, Italy

    Paola Maria Cutroneo

  2. Clinical Pharmacology Unit, University Hospital G. Martino, Messina, Italy

    Paola Maria Cutroneo, Claudia Giardina, Valentina Ientile & Gianluca Trifirò

  3. Pharmacovigilance Office, Italian Medicines Agency, Rome, Italy

    Simona Potenza & Laura Sottosanti

  4. Department of Experimental Medicine, Campania Regional Center of Pharmacovigilance and Pharmacoepidemiology, University of Campania, Naples, Italy

    Carmen Ferrajolo

  5. Department of Biomedical and Dental Sciences and Morpho-functional Imaging, University of Messina, Messina, Italy

    Costantino J. Trombetta & Gianluca Trifirò

Authors
  1. Paola Maria Cutroneo
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  2. Claudia Giardina
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  3. Valentina Ientile
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  4. Simona Potenza
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  5. Laura Sottosanti
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  7. Costantino J. Trombetta
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  8. Gianluca Trifirò
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Corresponding author

Correspondence to Paola Maria Cutroneo.

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Funding

This study was conducted as part of the multi-regional pharmacovigilance project “Short- and long-term monitoring of the benefit-risk profile of intravitreal use of anti-VEGF drugs through network of clinical and administrative data” funded by AIFA (CUP-H56D15000440005).

Ethical approval

The multi-regional pharmacovigilance project “Short- and long-term monitoring of the benefit-risk profile of intravitreal use of anti-VEGF drugs through network of clinical and administrative data” was notified to local ethical committees.

Conflict of interest

Paola M. Cutroneo, Claudia Giardina, Valentina Ientile, Simona Potenza, Laura Sottosanti, Carmen Ferrajolo, Costantino J Trombetta, Gianluca Trifirò have no conflicts of interest that are directly relevant to the content of this study.

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Cutroneo, P.M., Giardina, C., Ientile, V. et al. Overview of the Safety of Anti-VEGF Drugs: Analysis of the Italian Spontaneous Reporting System. Drug Saf 40, 1131–1140 (2017). https://doi.org/10.1007/s40264-017-0553-y

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  • DOI: https://doi.org/10.1007/s40264-017-0553-y