Risk of Ophthalmic Adverse Effects in Patients Treated with MEK Inhibitors: A Systematic Review and Meta-Analysis

Abstract

Objectives: This meta-analysis aims to evaluate the risk of ophthalmic adverse effects associated with MEK inhibitors.

Methods: A literature search was conducted in PubMed and the Cochrane Library to identify randomized clinical trials (RCTs) which have been designed to evaluate the efficacy and safety of MEK inhibitors. Overall risk of ophthalmic adverse effects, chorioretinopathy, retinal detachment, blurred vision, uveitis, and eye haemorrhage were the assessed outcomes. Peto odds ratios (ORs) with their 95% confidence intervals (CIs) were pooled. Between-study heterogeneity was assessed using I2 statistics.

Results: Thirteen RCTs were included in this meta-analysis. Overall, MEK inhibitors were associated with an increased risk of ophthalmic adverse effects (OR 2.24; 95% CI 1.75-2.87; p < 0.0001; I2 = 86.5%). An increased risk was also estimated for chorioretinopathy (OR 5.44; 95% CI 2.89-10.23; p < 0.0001; I2 = 0%), retinal detachment (OR 6.54; 95% CI 3.28-13.03; p < 0.0001; I2 = 0%), and blurred vision (OR 2.30; 95% CI 1.50-3.54; p < 0.0001; I2 = 60.1%), but not for uveitis (OR 0.99; 95% CI 0.14-7.03; p = 0.991; I2 = 2.9%) or eye haemorrhage (OR 0.72; 95% CI 0.04-12.39; p = 0.824; I2 = 29.8%).

Conclusions: Treatment with MEK inhibitors seems to increase the risk of ophthalmic adverse effects. A need for monitoring the safety of this class of drugs exists. Regulators, clinicians, and other health care professionals must, together, be involved in this process.