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1-year results from the HORIZON open-label extension study of ranibizumab (Lucentis, Genentech) for the treatment of exudative age-related macular degeneration show that treatment beyond 2 years relatively is safe and well tolerated, but previously treated patients who received ranibizumab monthly for 2 years may be susceptible to loss of vision with less-frequent dosing during the third year of treatment.
Scottsdale, AZ-Results from analyses of data collected in the HORIZON study after 1 year indicate that most patients who begin intravitreal ranibizumab (Lucentis, Genentech) therapy for exudative age-related macular degeneration (AMD) need treatment beyond 2 years.
The ongoing therapy continues to be relatively safe and well tolerated, but its efficacy appears to wane, at least when administration is switched to an "as-needed" dosing regimen after the first 2 years, said SriniVas R. Sadda, MD, at the annual meeting of the Retina Society. He is associate professor of ophthalmology and director, Medical Retina Unit, Ophthalmic Imaging Unit, Doheny Image Reading Center, Doheny Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles.
Phase IIIb study
The HORIZON participants are patients who completed the 2-year monthly treatment phase of the three Genentech-sponsored phase III studies: MARINA, ANCHOR, and FOCUS.
They represent patients with all types of wet AMD who originally randomly were assigned to receive ranibizumab 0.3 mg or 0.5 mg, ranibizumab 0.5 mg plus photodynamic therapy (PDT), sham injection, or sham injection plus PDT. All patients who entered the extension study were eligible for treatment with ranibizumab 0.5 mg at up to 30-day intervals, which was given according to the investigator's discretion.
At the end of the first year of HORIZON, among patients who already had been treated for 2 years, only a very small minority (<3%) benefited with further moderate vision improvement. The average patient was susceptible to losing some vision (<1 line) over the course of the third year. Patients initially randomly assigned to receive sham or PDT who crossed over to ranibizumab also rarely showed evidence of moderate visual improvement.
"Perhaps by the end of 2 years we are seeing the effects of the natural history of the disease processsuch that there has been enough permanent damage to limit any effect of treatment on vision," Dr. Sadda said.
"Whether further improvement might be achieved if ranibizumab was administered on a routine monthly schedule remains unknown. HORIZON was not designed to answer the key question of what is the optimal regimen for ongoing treatment," he added.
Nevertheless, the data from the 1-year analysis in the HORIZON provide information that is useful for patient counseling and decision-making purposes, Dr. Sadda said.
"We can tell patients who are candidates for ranibizumab that it is very possible they might need to continue treatment into a third year," he said. "Taking into account their age, health status, vision in their fellow eye, and perhaps other factors, some patients may opt against treatment based on that knowledge.
"However, I hold the belief that the earlier treatment is begun, the better, and that is supported by the results of HORIZON comparing the outcomes in the groups treated originally and those who crossed over to treatment at a later time," he added. "Therefore, we can also counsel patients that they have a chance of improving vision if treatment is begun, but they may lose that chance if they wait."
About 85% of patients enrolled in the three phase III studies and reached the 2-year visit, and about 80% of those patients elected to enroll in HORIZON. The proportion of HORIZON enrollees who reached the 1-year visit also was around 84%. The most common reason for discontinuation from HORIZON was that the patient desired to exit the study.
Of the 853 patients who entered HORI-ZON, 600 had received ranibizumab alone or with PDT from the outset, 168 initially randomly assigned to receive a sham injection or PDT were crossed over to ranibizumab either near the end of the initial study or in HORIZON, and 85 patients never received ranibizumab.