Meta-analysis gives intravitreal ranibizumab vascular adverse risk profile

Feb 13 2015

By Lynda Williams, Senior medwireNews Reporter

Intravitreal ranibizumab treatment for age-related macular degeneration (AMD) does not elevate the risk of mortality, suggests a meta-analysis published in Ophthalmology.

However, analysis of results from 11 clinical trials including 6596 AMD patients treated at varying doses of the vascular endothelial growth factor (VEGF) inhibitor did find a “possible relationship” between increasing treatment intensity and risk for systemic vascular adverse events.

Specifically, a 0.5 mg dose was associated with a significantly higher risk of cerebrovascular accidents (CVAs) than a 0.3 mg or 0.0 mg dose (odds ratio [OR]=1.86), as was a monthly versus pro re nata dose or no treatment (OR=1.89).

The risk of nonocular haemorrhage was also significantly higher for patients given a 0.3 mg or 0.5 mg dose versus no treatment (OR=1.57), report Takashi Ueta, from the University of Tokyo in Japan, and co-authors.

Trends were also identified for an increased risk of CVA at 0.5 mg versus no dose, and a monthly versus pro re nata dose, as well as higher risk of nonocular haemorrhage for a 0.5 mg or 0.3 mg versus no dose or a monthly dose versus pro re nata therapy or no treatment, although these risks did not reach statistical significance.

Monthly ranibizumab at any dose was associated with a trend towards an increased risk of arterial thromboembolic events compared with pro re nata therapy or no treatment but again this outcome was not significant.

And the researchers found no indication to suggest that the risk of myocardial infarction was affected by ranibizumab dose or treatment timing.

“[T]hese findings present a dilemma because an 0.5-mg dose of ranibizumab is the most commonly used in clinical practice, and frequent retreatment is often necessary to maintain visual acuity in some patients”, the researchers observe, noting the intravitreal dose is smaller than that given for intravenous VEGF inhibitors.

“Nonetheless, our meta-analysis results suggest that even a small anti-angiogenic insult may produce an effect in patients with exudative AMD.”

The team hypothesises that patients may become more vulnerable to cerebrovascular insult after the age of 75 years and that the risk may be in part to the physical proximity of the vitreous cavity and the subarachnoid space.

“Therefore, future studies to discern the mechanisms of how intravitreal ranibizumab affects the cerebrovasculature are warranted”, Ueta et al write.

Further research could also compare the risk of such adverse events for AMD patients using ranibizumab with those given other agents such as the VEGF inhibitor aflibercept and the angiogenesis inhibitor bevacizumab, they conclude.

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