Genetic biomarkers of ranibizumab response remain elusive in Koreans with AMD

May 1 2014

By Lucy Piper, Senior medwireNews Reporter

Researchers have failed to find a significant genotypic effect on ranibizumab treatment response in Korean patients with neovascular age-related macular degeneration (AMD).

None of the 23 polymorphisms in 12 genes previously identified as being genetic risk factors for AMD were shown to be associated with favourable visual outcome 5 months after monthly intravitreal injections of ranibizumab 0.05 mL.

The only exception was the AA genotype of VEGF polymorphism rs699947. Carriers of this genotype were a significant 3.6-fold more likely to have a good treatment response at 5 months than carriers of the CC and CA genotypes. This was true in multivariate analysis adjusting for factors such as lesion area, central retinal thickness and baseline Early Treatment Diabetic Retinopathy Study (ETDRS) letter score, but only when uncorrected for multiple testing with the Bonferroni method.

Ranibizumab is a monoclonal antibody that neutralizes biological forms of VEGF, so the influence of VEGF polymorphisms on ranibizumab response is likely to be mediated through VEGF production, the research team explains.

Although unable to find a genetic biomarker for treatment response to ranibizumab, the researchers say that the study, published in Retina, did confirm the drug’s therapeutic effect in a Korean population.

For the 273 treatment-naïve patients who received ranibizumab, visual acuity improved by 9.1 ETDRS letters by month 5 and 136 (49.8%) patients were considered to be good responders, defined as having a visual improvement of at least 8.0 ETDRS letters.

The average central retinal thickness decreased from 316.6 µm to 250.4 µm and the average total area of choroidal neovascularisation decreased from 3.7 to 3.1 disk areas. Improvement in these two outcomes was significantly greater for good responders than for poor responders, notes the team, led by Hyeong Gon Yu (Seoul National University College of Medicine, Korea).

However, there was no significant difference between good and poor responders for angiographic response – clinically dry without active leakage from choroidal neovascularization in fluorescein angiography. Given this discrepancy, the researchers also assessed whether any of the polymorphisms were significantly associated with a good angiographic response, but found no associations.

“[T]his study only reflects the early response to predetermined monthly injection schedule”, caution Yu and colleagues. “After long-term follow-up with an individualized injection schedule with an as-needed regimen, the genetic profile associated with the final visual outcome could be different.”

The effects of such an as-needed protocol are currently being studied by the group, and they hope that the findings will “give a clearer perceptive on the pharmacogenetic association of ranibizumab for neovascular AMD.”

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