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Of three anti-vascular endothelial growth factor (VEGF) drugs used to treat several serious eye diseases, there was no substantially different relative risk for kidney failure, a retrospective cohort study suggested.

Among over 240,000 adult patients who took intravitreal anti-VEGF medications for diabetic retinopathy, diabetic macular edema, exudative age-related macular degeneration, or retinal vein occlusion, Cindy X. Cai, MD, of Wilmer Eye Institute at Johns Hopkins University in Baltimore, and colleagues reported in that the meta-analysis hazard ratio of kidney failure was:

• 1.01 (95% CI 0.70-1.47, P=0.45) for aflibercept (Eylea) versus ranibizumab (Lucentis)
• 0.95 (95% CI 0.68-1.32, P=0.62) for ranibizumab versus bevacizumab (Avastin)
• 0.95 (95% CI 0.65-1.39, P=0.60) for aflibercept versus bevacizumab

"There are no differences, which is great," Cai told 番茄社区app. "Prior to this study, some of us were perhaps preferentially choosing ranibizumab over aflibercept in our patients with diabetes who are at high risk for having kidney failure. Now, we can let other factors guide our treatment."

Brian L. VanderBeek, MD, MPH, of the Scheie Eye Institute at the University of Pennsylvania in Philadelphia, who wasn't involved with the study, told 番茄社区app that anti-VEGF agents are the primary form of treatment for age-related macular degeneration, diabetic macular edema, and macular edema due to retinal vein occlusions.

"Clinical trials have shown their superiority to all other treatments with regard to visual acuity outcomes and ocular safety profile," he said. "There really is not a true peer alternative to give that can safely improve vision in the way anti-VEGF agents do."

As for renal risk, it's "very much up for debate" as to whether the tiny doses of anti-VEGF drugs given intravitreally endanger the kidneys, he noted.

According to Cai, this study doesn't address that overall question but instead examines whether there's an overall difference in risk between the drugs. There has been speculation that ranibizumab poses a lower risk because it has fewer systemic side effects, she said.

The findings "free [up] the physician to choose one medicine versus the other for other reasons" besides kidney risk, she added.

VanderBeek said that "very few studies can be definitive, but this study definitely enhances my confidence that there is no difference between medications with regard to kidney risk."

As for expense, Cai said that anti-VEGF drugs can be costly. According to of Medicare data for patients with age-related macular degeneration, the average cost per unit of bevacizumab (off-label) in 2020 was $76.32 compared with $923.56 for aflibercept and $333.55 for ranibizumab.

For this study, the researchers analyzed data from the Observational Health Data Sciences and Informatics network on 6.1 million patients with four blinding diseases and focused on those who were newly treated with anti-VEGF agents and had received at least 3 monthly treatments. Of those, 37,189 received ranibizumab, 39,447 received aflibercept, and 163,611 received bevacizumab. The total treatment exposure time was 161,724 person-years.

Across the groups, most patients were 70-89 years old (70-74%), 59-61% were women, 72-76% were white, and 8-10% were Black. Most patients had age-related macular degeneration (57-64%).

The average standardized incidence proportion of kidney failure was 678 per 100,000 persons, and the incidence rate was 743 per 100,000 person-years.

"The higher incidence of kidney failure identified in this study is likely due to differences in the underlying study population when compared to the overall population," Cai and team wrote. "Patients treated with anti-VEGF are older and often have cardiometabolic risk factors like diabetes that put them at higher risk for kidney disease."

In regard to limitations, the researchers highlighted their reliance on electronic health record/claims data, and they noted that the data don't include information about dosages.

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