About 20% of patients in the trial of a high-dose, longer-interval regimen of Eylea (aflibercept )switched to shorter intervals, according to data presented today at the American Society of Retinal Specialists annual scientific meeting, which is being held in Seattle. Researchers didn't find any clues as to why in their baseline characteristics.
Results from the PULSAR study show that about 80% of the wet age-related macular degeneration (AMD) patients randomized to regimens of higher but less frequent doses of Eylea (aflibercept) stayed on those regimens.
But based on certain predetermined criteria that their AMD was worsening, 20% were switched to more frequent dosing, and the presentations during a morning session of the American Society of Retina Specialists annual scientific meeting and a lively discussion afterward showed that there are many unanswered questions about the characteristics of the patients that need to be switched, and the criteria that retina specialists should use in everyday clinical practice to change dosing.
“I think the resounding message from these talks is essentially that, at least from the PULSAR data, that we don't really know who are the 20% of patients that are going to really need higher doses of medication — and that’s where we need help,” said David R. Chow, M.D., director of the Toronto Retina Institute and an assistant professor at St. Michael’s Hospital, University of Toronto.
The much-discussed PULSAR study compared wet AMD patients treated with the currently approved 2-mg dose of Eylea every eight weeks to an 8-mg dose every 12 weeks and an 8-mg every 16 weeks.The results reported so far show that the 8-mg dose injected less often is as safe and effective (noninferior) to the 2-mg dose every eight weeks.
The data that Chow presented showed that 79% of the patients in the group treated with 8-mg every 12 weeks stayed on that schedule of injections and that 77% of those receiving the 8-mg injections every 16 weeks did so. Chow and his colleagues compared the baseline best-corrected visual acuity (BCVA), the central subfield retinal thickness and the choroidal neovascularization lesion area of the those who stayed on the 12-week and 16-week schedules and those who were switched to the more frequent 8-week intervals. They found no meaningful differences and concluded that baseline characteristics did not appear to be associated with staying on the longer interval or switching to the shorter one.
Chow’s results and questions from Ursula Schmidt-Erfurth, M.D., a professor and chair of the Department of Ophthalmology at the University Eye Hospital in Vienna, Austria, after his talk led to a discussion of the criteria used to decide whether patients need to be switched to shorter intervals, how that criteria can color the results of trials assessing longer intervals and how it relates to what retinal specialists do in the real-world practice.
“I think that we are all struggling a little bit with the criteria for retreatment,” said Schmidt-Erfurth. “There's such a wide spectrum, particularly suggested lately in these longer durability, longer interval trials.”
Chow had mentioned in his talk that the criteria for switching in the PULSAR trial was a loss of visual acuity (a 5-letter loss in BCVA) and a 25-micron increase in CST (central subfield thickness) or new onset of foveal neovascularization or foveal hemorrhage.
Chow and Jignesh I. Patel, M.D., who also presented PULSAR data, said they didn’t necessarily follow that criteria in clinical practice.
“The dosing modification requirement, in my opinion, have often been higher than what I would do in my everyday clinical practice,” Chow said.
One of the moderators, Jeff S. Heier, M.D., co-president of Ophthalmic Consultants of Boston, a large, prestigious specialty ophthalmology practice in Boston, said he does not depend on visual acuity measurements to make treatment adjustment because it fluctuates. Heier said he treats according to fluid.