Carl D. Regillo, MD, FACS; Blake Anthony Cooper, MD, MPH; Michael A. Klufas, MD; and David R. Lally, MD, consider the implications of real-world evidence indicating fewer visual gains associated with anti-VEGF therapies compared with clinical trials.
Carl D. Regillo, MD, FACS: Blake, the anti-VEGF drugs we have had performed well in clinical trials. On average, vision gains are well maintained over 1 to 2 years with frequent, regular treatment. In practice, we like to utilize these drugs in various ways. We’ve talked about how we try to individualize therapy, but how are we doing in the real world [regarding] visual outcomes with the use of anti-VEGF for neovascular age-related macular degeneration [AMD] and diabetic macular edema [DME]?
Blake Anthony Cooper, MD, MPH: It’s a great question, Carl. A clinical trial is an ideal situation where patients are followed at a regular interval with a treatment that is set. As patients come into our office, often we are looking at ways to modify what would be an FDA-indicated dosing schedule. In real world studies, we’re having suboptimal visual outcomes because we are most likely undertreating patients. For [DME], patients continue to improve through the first year if they are getting monthly injections and it’s often rare for patients to have 10 injections within the first year. Often we will treat and start to extend personalized treatment interval…but studies routinely show that patients tend not to have the visual gains we would expect from a clinical trial, unfortunately. It points to the need for more durable treatment options and hopefully as we evolve with our medications, we will have that for our patients.
Carl D. Regillo, MD, FACS: I’m glad you tied in durability to the suboptimal real world visual outcomes because when we talk about durability individuals usually think decreasing treatment burden, and that’s true. That’s a favorable thing our patients would welcome but we all hope it also is going to translate into better long-term vision outcomes, fewer recurrences, and therefore patients will be better able to maintain those vision gains that we get often only in the front part of the treatment regimen.
Blake Anthony Cooper, MD, MPH: Correct.
Carl D. Regillo, MD, FACS: Mike, what are the reasons behind this adherence issue we have with our anti-VEGF therapy to treat DME and neovascular AMD?
Michael A. Klufas, MD: It’s a simple answer. Life happens: patients switch insurances; they may need to go in for an emergency stent procedure; they may want to go on vacation or go to their son or daughter’s wedding and extend the treatment interval; financial issues; or lack of being able to get transportation for the visit. All these things contribute to not being able to administer treatment potentially every 4 or 6 weeks. Even if you had neovascular AMD, you might not be able to come in every 6 weeks…and so we have to take these things into account and expect what we are going to get in reality. That’s where…we have come into play as retina specialists to increase the durability. We have done things such as treat and extend that offer slightly less visual benefit but still acceptable and provide robust vision gains to our patients but allow us to have more flexibility with the dosing with current agents. We are hoping to have more durable agents to accommodate different life changes for our patients who may not be able to come in so frequently.
Carl D. Regillo, MD, FACS: In clinical trials, results are typically good because patients are self-selected for being able to come in and adhere to the frequent treatment regimens. But in the real world, things get in the way and in our neck of the woods it could be a snowstorm too; you didn’t mention that. Transportation is probably high on the list, especially for our elderly patients who rely on other individuals to bring them into the office. The patients who have diabetic retinopathy are a bit younger, often working, and work schedules can interfere with their ability to get into our office on a frequent, regular basis. These injections…need to be done on a frequent, regular basis. Blake, what are the unmet needs observed with the current treatment options for the management of DME and neovascular AMD?
Blake Anthony Cooper, MD, MPH: We’ve touched on it quite a bit as far as patients being able to come in monthly for injections and the treatment burden that puts on them, their caregivers, and the physicians treating them. It’s important, from our understanding of the disease state, with diabetes and macular degeneration. Often, if we can slow the onset of the disease, this and glycemic control may help prevent the development of diabetic retinopathy. We’re hopeful, as we have more durable medications, that they will reduce the frequency of injections. We are having the option to deliver the medications in a different manner, either surgically…possibly oral medications or eye drops will be able to help our patients. But it’s still a burden for our patients having intravitreal injections on a regular interval.
Carl D. Regillo, MD, FACS: You’re right in line with what our most recent surveys from the American Society of Retina Specialists indicate that No. 1 unmet need is anti-VEGF therapeutics that last longer. Again, decrease the treatment burden, maybe even get better long-term vision outcomes for both these conditions.
Transcript Edited for Clarity