Fran Lowry

May 10, 2012

May 10, 2012 (Fort Lauderdale, Florida) — High-dose ranibizumab (Lucentis) does not provide better visual acuity than standard-dose ranibizumab in newly diagnosed wet age-related macular degeneration (AMD), according to results from the HARBOR study, presented here at the Association for Research in Vision and Ophthalmology 2012 Annual Meeting.

"Lucentis 0.5 mg monthly is at the top of the dose–response curve; there is no additional benefit from the high dose [2.0 mg] in treatment-naïve wet AMD patients," lead author Ivan J. Suner, MD, from Retina Associates of Florida in Tampa, told Medscape Medical News.

To compare the efficacy and safety of the 2 doses, the HARBOR researchers randomized 1097 patients with subfoveal wet AMD who were 50 years or older to ranibizumab injections (either 2.0 mg or 0.5 mg) dosed monthly or on an as-needed (PRN) basis after 3 loading doses.

At 12 months, all 4 treatment groups had significant and clinically meaningful increases in best-corrected visual acuity. Patients randomized to 0.5 mg ranibizumab monthly gained 10.1 letters, those randomized to 2.0 mg monthly gained 9.2 letters, those randomized to 0.5 mg PRN gained 8.2 letters (with an average of 7.7 injections), and those randomized to 2.0 mg PRN gained 8.6 letters (with an average of 6.9 injections).

The proportion of patients who lost more than 15 letters from baseline in the 4 groups was similar. For 0.5 mg monthly, that proportion was 97.8%; for 2.0 mg monthly, it was 93.4%; for 0.5 mg PRN, it was 94.5%; and for 2.0 mg PRN, it was 94.9%.

The mean change from baseline in central foveal thickness was –172.0 µm for 0.5 mg monthly, –163.3 µm for 2.0 mg monthly, –161.2 µm for 0.5 mg PRN, and –172.4 µm for 2.0 mg PRN.

Ocular serious adverse events were rare in all treatment groups, and no new safety signals were identified, Dr. Suner said.

Ocular adverse events were balanced among the treatment groups, he said.

The most common ocular adverse event was conjunctival hemorrhage, occurring in 18% of patients overall. Intraocular pressure increased in 11 patients (4%) treated with 0.5 mg monthly, in 5 patients (1.8%) treated with 0.5 mg PRN, in 7 patients (2.6%) treated with 2.0 mg monthly, and in 6 patients (2.2%) treated with 2.0 mg PRN.

In addition, 4 patients (0.4%) developed glaucoma, which was medically controlled.

"Doctors can now tell their patients that standard-dose [ranibizumab] provides the best efficacy and safety. Using a PRN regimen with monthly monitoring may lead to the loss of a few letters of vision, compared to monthly injections, but it may reduce the expense of the medication and the treatment burden of injections," Dr. Suner said. "Using less drug produced no significant difference in systemic side effects, [but] would reduce the risk of injection-related complications, such as endophthalmitis."

Commenting on this study for Medscape Medical News, Roger A. Goldberg, MD, MBA, from the Bascom Palmer Eye Institute at the University of Miami in Florida, pointed out that high-dose ranibizumab did not meet the noninferiority criteria for the HARBOR study.

"If it had, it would have given clinicians an option to dose [ranibizumab] at a frequency similar to that of [aflibercept], which is dosed every 8 weeks after an induction phase. Clinicians are looking for ways to decrease the number of injections needed for patient maintenance," said Dr. Goldberg, who was not part of the HARBOR trial.

He added that the fact that there were no dose-related safety concerns with the 2 doses of ranibizumab "provides yet another data point corroborating, in general, the safety of anti-VEGF agents in the treatment of macular degeneration."

Dr. Suner reports a financial relationship with Genentech. Dr. Goldberg has disclosed no relevant financial relationships.

Association for Research in Vision and Ophthalmology (ARVO) 2012 Annual Meeting: Abstract 3677. Presented May 8, 2012.


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