Aflibercept for DME effective therapy in VISTA, VIVID trials

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Data from the phase III VISTA-DME trial show aflibercept 2 mg every 4 or every 8 weeks remains superior to laser photocoagulation and is associated with stable improvements in best-corrected visual acuity and macular thickness.

By Cheryl Guttman Krader; Reviewed by David M. Brown, MD

Houston-Ongoing treatment of diabetic macular edema (DME) with intravitreal aflibercept 2 mg (Eylea, Regeneron) at 4- or 8-week intervals (2q4 or 2q8) is associated with sustained functional and anatomic benefit during follow-up approaching 2 years, according to data from the U.S. phase III VISTA-DME trial.

“These data indicate aflibercept is a very effective treatment for DME, and the most encouraging aspect of the findings is that eyes receiving injections every other month maintained excellent visual acuity gains through 2 years,” said David M. Brown, MD, retinal specialist at Retina Consultants of Houston and Houston Methodist Hospital.

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“If the 2q8 regimen is undertreating the disease, we would expect to see the benefit decline as the treatment duration increases,” Dr. Brown said. “However, there was little change in the BCVA improvement between 1 and 2 years, suggesting that every other month injections with aflibercept after an initial loading course might be sufficient for the average patient needing treatment for DME.”

NEXT: More about VISTA-DME

More about VISTA-DME

The double-masked study randomly assigned 466 patients 1:1:1 to receive aflibercept 2q4, aflibercept 2q8 (after 5 initial consecutive monthly doses), or laser photocoagulation. Mean change in ETDRS best-corrected visual acuity (BCVA) from baseline to week 52 was assessed as the primary efficacy endpoint. The analysis showed statistically significant differences favoring both the aflibercept 2q4 and 2q8 groups compared with laser (12.5 and 10.7 versus 0.2 letters).

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Dr. Brown presented results from follow-up to 100 weeks. At week 100, BCVA was improved from baseline by a mean of 11.5 and 11.1 letters in the aflibercept 2q4 and 2q8 arms and by 0.9 letters in the laser-treated control group, he noted.

Mean reductions in optical coherence tomography-measured center macular thickness were also significantly greater in the aflibercept arms than in the laser group at week 52, and the aflibercept groups maintained their treatment benefit at 1 year.

Patient retention through week 100 ranged from 80% to 85% across the three treatment arms. The mean number of treatments received during the first 100 weeks of the study was 3.5 in the laser group, 21.3 in eyes receiving aflibercept 2q4 and 13.5 in the aflibercept 2q8 group.

Rescue treatment was given if a patient had a BCVA loss ≥15 letters at any visit or a loss ≥10 letters at two consecutive visits. The proportion of patients receiving rescue treatment was 41% in the laser group, but only 3.2% in the aflibercept 2q4 arm and 8.6% in aflibercept 2q8 group.

NEXT: Analyses of BCVA change

Analyses of BCVA change

Other analyses showed that about three times as many patients in the aflibercept 2q4 and 2q8 groups compared with controls had a ≥15 letter gain from baseline at week 100 (38% and 33% versus 13%).

Dr. Brown said that even more noteworthy, aflibercept was superior to laser in preventing significant vision loss. At week 100, the proportion of eyes losing ≥15 letters from baseline BCVA was significantly lower in the aflibercept 2q4 and 2q8 groups compared with the controls (3.2% and 0.7% versus 9.7%).

In addition, more than twice as many aflibercept-treated patients compared with controls had an improvement of 2 or more steps in the Diabetic Retinopathy Severity Score (37% versus 15.6%).

No new ocular safety signals emerged for aflibercept during the second year of the study, and there were fewer inflammatory events in the aflibercept 2q4 and 2q8 groups compared with the controls (0.2% and 0.1% versus 0.4%), reflecting the development of iris neovascularization in more laser-treated eyes.

Rates of Antiplatelet Trialists’ Collaboration-defined arterial thromboembolic events were 6% in the laser arm and 7.8% in the pooled aflibercept arms; mortality rates were 2% in the laser arm and 4% for aflibercept.

NEXT: Conclusion

It is unclear if the difference in rates of these events between treatment groups reflects sample variation or some systemic effect of aflibercept that may be more pronounced in this vasculopathic patient population, he noted.

“Another point to recognize is that about two-thirds to three-fourths of patients across all treatment arms received aflibercept to treat DME in the fellow, non-study eye,” Dr. Brown said. “This would increase systemic aflibercept exposure and magnify any potential systemic adverse event rate in this population being treated in both eyes.

“Forthcoming data from the international VIVID-DME trial of aflibercept may provide more insight on these questions,” he added.

David M. Brown, MD

E: dmbmd@houstonretina.com

Dr. Brown is a consultant to Regeneron and helped to design the VISTA-DME AND VIVID-DME trials. He is also a consultant and investigator for Allergan and Genentech.