Aflibercept fares well in treating DME


Intravitreal aflibercept 2 mg every 8 weeks after 5 initial monthly doses (IVT-AFL 2q8) improved visual acuity outcomes in eyes with center-involved diabetic macular edema (DME) to a greater extent than intravitreal ranibizumab 0.5 mg as needed (IVR 0.5 mg PRN), though vascular endothelial growth factor (VEGF) inhibition with either IVT-AFL or IVR is efficacious and appears safe

Intravitreal aflibercept (Eylea, Regeneron Pharmaceuticals) was found to improve visual acuity outcomes in eyes with diabetic macular edema (DME), more so than intravitreal ranibizumab (Lucentis, Genentech), according to findings published in BMC Ophthalmology.

Findings of the systematic review and mixed treatment comparison of aflibercept with other therapies for DME also reported that vascular endothelial growth factor (VEGF) inhibition with either aflibercept or ranibizumab is efficacious and appears safe. Aflibercept was associated with a trend toward fewer adverse ocular events compared with dexamethasone 0.7 mg implants.

Researchers from France, the Netherlands, the United Kingdom,. and the United States undertook a comprehensive search to source relevant studies. They prepared feasibility networks to identify viable comparisons of 12-month outcomes between aflibercept and therapies licensed outside the United States, and then assessed them for clinical and statistical homogeneity.

Pooled effect sizes (mean difference [MD] and relative risk/risk ratio [RR]) were calculated, using fixed- and random-effects models. Indirect comparisons were performed using Bucher analysis. If at least one head-to-head study was found, a mixed treatment comparison (MTC) was performed using Bayesian methods.

Two 12-month comparisons could be undertaken based on indirect analyses: aflibercept (2 mg every 8 weeks after 5 initial monthly doses) versus ranibizumab (0.5 mg as needed) (10 studies) and aflibercept versus dexamethasone (three studies).

The researchers found that there was an increase in mean best-corrected visual acuity (BCVA) with aflibercept over ranibizumab by 4.67 letters  in the fixed-effect MTC model (10 studies) and by 4.82 letters  in the Bucher indirect analysis (four studies). Aflibercept doubled the proportion of patients gaining ≥ 10 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at 12 months compared with dexamethasone in the fixed-effect model. There were no significant differences in safety outcomes between aflibercept and ranibizumab or dexamethasone.

The researchers concluded that studies of aflibercept showed improved 12-month visual acuity measures compared with studies of ranibizumab and dexamethasone based on indirect comparisons.


The evidence from these specific comparisons showed a benefit of aflibercept over ranibizumab for the improvement of mean change from baseline in BCVA (+4.67 letters before adjustment for baseline visual acuity and +4.12 after adjustment), and that about 70% fewer patients showed a loss of ≥ 10 ETDRS letters. These results were consistent in multiple analyses, including both MTC analyses (3,060 DME patients) and in Bucher analyses (1,611 DME patients), and remained consistent when one study in Asian patients was included or excluded from the Bucher analysis. There were no significant differences between aflibercept and ranibizumab in safety outcomes.

The evidence also favored aflibercept over dexamethasone in an indirect analysis of three studies with 1,123 DME patients. More patients (about twice as many) receiving aflibercept showed a gain of ≥ 10 ETDRS letters compared with those receiving dexamethasone. There were also fewer patients treated with aflibercept who experienced increased IOP compared with dexamethasone. There were an additional five safety outcomes (macular edema, reduced visual acuity, vitreous hemorrhage, eye pain and cataract) that showed a non-significant trend in favor of aflibercept.


“Although the study has a number of strengths, including the adherence to international guidelines for performing indirect analyses, inclusion of prespecified inclusion and exclusion criteria, and comprehensive assessment of clinical and statistical heterogeneity, it does have a number of limitations inherent with indirect analyses, the scope is narrow, and the conclusions must be interpreted with caution,” the researchers noted.

“Many studies had unclear or high risk of bias in at least one domain of the Cochrane risk of bias tool, and safety outcomes were limited by differences in definitions of events,” they added. “The number of events reported across studies was low, and the CIs were wide. There is a need for more studies comparing the relative effects of licensed therapies for DME in order to select the best treatment options for our patients.”

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