Best frequency for neovascular AMD treatment still unknown

November 1, 2007

Management of patients with neovascular age-related macular degeneration has evolved, but clinicians are at a crossroads when considering continuation of treatment. Evidence suggests that monthly treatment and less frequent treatment regimens are better than no treatment. The best treatment regimen remains elusive.

Key Points

Baltimore-Following the clinical trials of ranibizumab (Lucentis, Genentech), changing the course of treatment in patients with choroidal neovascularization (CNV) began to be considered.

Ophthalmologists must decide when to continue treating CNV, when to withhold treatment, and whether treatment should be administered every month for 2 years if there are 125,000 people who develop the disease annually in the United States. The number of treatments ophthalmologists face is staggering, said Neil Bressler, MD, who is the James P. Gills Professor of Ophthalmology and chief of the retina division at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore.

"Our burden has clearly changed in terms of treating neovascular age-related macular degeneration (AMD)," he said.

PDT was not a continuous treatment to be guaranteed every 3 months. The trials that showed a beneficial effect of PDT indicated that if leakage from CNV was still seen on fluorescein angiography, then treatment could be applied as often as every 3 months. "In some cases, leakage stopped and treatment was no longer necessary. On average, patients were treated five to six times over a 2-year period and very infrequently thereafter," Dr. Bressler stated.

The advent of the anti-vascular endothelial growth factor (VEGF) drugs resulted in a sea change in treatment. Initially, pegaptanib (Macugen, Pfizer) showed a reduction in the risk of losing 15 or more letters compared with no treatment in the VISION Trial, but even greater efficacy was shown with ranibizumab in the ANCHOR and MARINA trials.

"With ranibizumab, we not only were able to halt at least 15 letter loss in 90 to 95% of cases, but in 30 to 40% of cases, visual acuity improved at least 15 letters compared with 5% of control subjects," he said.

The change associated with anti-VEGF drugs is that treatment can be administered as often as every 4 weeks. Vision can be preserved at the 20/40 or better level in many patients if it is initiated before much vision loss has occurred and some patients have improved vision, but the question of how often to treat arises.

Frequency of treatment

With PDT, Dr. Bressler said, loss of visual acuity was avoided in two-thirds of cases when treatment was applied as often as every 3 months. With ranibizumab, vision loss was avoided in 95% of cases with monthly treatment. Right now, it is unknown whether providing treatment slightly less often, such as monthly for 3 months and then less frequently, will result in worse, almost as good, or better visual acuity results. Dr. Bressler hypothesized about a scenario in which two cases out of 10 (20%) do not avoid 15 or more letter loss with less-than-monthly dosing compared with 1 out of 20 (5%) with monthly dosing. Most clinicians likely could not detect those differences in their practices, but it might not be appropriate to increase this risk from 5% to 20%.

"We just do not know at this time if applying the drug slightly less often will necessarily decrease the treatment effect a great deal. Treatment could be decreased slightly and still result in a better effect than with PDT but not have as good an effect as with monthly treatment," he said.

In the PIER trial of ranibizumab, when the drug was given for 3 months and then every 3 months, subjects treated with ranibizumab were more likely to avoid 15 or more letter loss compared with controls. This regimen, however, was not compared with monthly treatments as was done in the MARINA and ANCHOR trials, so outcomes of one trial cannot be compared easily with outcomes of the other trial.

"The optimal duration of treatment remains undetermined," Dr. Bressler said.