Reporting of Safety Events during Anti-VEGF Treatment: Pharmacovigilance in a Noninterventional Trial.

Focke Ziemssen,Joachim Wachtlin,Hüsnü Berk,Maria-Andreea Gamulescu,Bettina Mueller,Jessica Voegeler,Ocean Study Group Ocean Study Group,Thomas Hammer,Matthias Grueb,Miguel Rechichi

doi:10.1155/2020/8652370

Abstract

Aim The prospective, noninterventional OCEAN study assessed the safety of intravitreal ranibizumab injections for treatment of neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusion under real-world conditions in Germany. Methods Adults receiving ≥1 ranibizumab (0.5 mg) injections were recruited by 369 ophthalmologists and followed for 24 months. Information on adverse events (AEs) was reported by the treating physician or detected by the data management team. Collected information included observed AE, AE start and end date, intensity, causal relationship, outcome, severity, suspected drug, and actions taken. Results 2,687 AEs were reported for 1,176 of the 5,781 patients who had received a total of 32,621 injections: 27.4% nonserious AEs, 30.3% serious AEs, 27.3% nonserious adverse drug reactions (ADRs), and 15.0% serious ADRs. Most patients reported no AEs (79.7%) or only 1 AE (10.3%). AEs were most commonly reported in the Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC) Eye disorders (9.4% of patients) and General disorders and administration site conditions (5.8%). The most frequent AEs by MedDRA preferred term (PT) were visual acuity reduced (3.5% of patients), intraocular pressure increased (2.5%), and drug ineffective (2.1%). AEs occurred most frequently after 3 or 4 injections (1,129 of 2,687 AEs). The proportion of AEs in the SOC Eye disorders decreased slightly with increasing number of injections, from 39.8% of events after 1 or 2 injections to 29.1% after 5 or more injections. Rates of the most frequently reported PTs did not show any consistent increase with increasing number of injections. A decrease in overall AE rates was observed over the study course. Conclusions The results did not raise any new safety concerns for ranibizumab. The findings allow conclusions to be drawn on how pharmacovigilance data can be collected even more effectively in real-world studies to facilitate discussion on benefit-risk ratio.

Highlights

adverse events (AEs) were most commonly reported in the Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC) Eye disorders (9.4% of patients) and General disorders and administration site conditions (5.8%). e most frequent AEs by MedDRA preferred term (PT) were visual acuity reduced (3.5% of patients), intraocular pressure increased (2.5%), and drug ineffective (2.1%)
A number of studies have addressed the safety of vascular endothelial growth factor (VEGF) inhibition for the treatment of neovascular age-related macular degeneration, diabetic macular edema (DME) [1,2,3], and retinal vein occlusion (RVO) [4, 5]
It is important to be aware that certain comorbidities have been associated with the risk of the treatment indications [8, 9]; for example, cardiovascular risk factors cause venous occlusion [10], or poorly controlled blood pressure/blood sugar contributes to DME [11]. is makes older patients with neovascular or edematous retinal disease—especially the sicker ones outside the selection of randomized controlled trials (RCTs)—“risk patients” in routine clinical practice [12]

Summary

Introduction

A number of studies have addressed the safety of vascular endothelial growth factor (VEGF) inhibition for the treatment of neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME) [1,2,3], and retinal vein occlusion (RVO) [4, 5]. Anti-VEGF drugs for the treatment of retinal conditions are in general well tolerated, a number of ocular adverse events (AEs) are known to occur after intravitreal injections [6, 7]. The increased risk of AEs and ADRs in the aged population is characterized by age-related changes in drug pharmacodynamics and pharmacokinetics and a large number of different risk factors and comorbidities [26]. E present analysis examines the safety in a large noninterventional study, aiming to provide further estimates for the safety profile of VEGF inhibition in ophthalmological indications. e analysis was undertaken to question and improve the methods for the acquisition of safety signals within the framework of Phase IV studies

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Conflicts of Interest