Clinical Management of Diabetic Macular Edema - Episode 9
Dr Joseph M. Coney reviews his personal experience using anti-VEGF agents to treat diabetic macular edema in his clinical practice.
Nancy Holekamp, MD: Dr Rahimy noted that we have clinical trials where we use fixed-interval dosing for patients with diabetic macular edema [DME], and we have wonderful results, but when we try to translate that into our clinics, into the real world, we have challenges. It is a challenging patient population and to keep up with monthly or every other month injections. Dr Coney, what’s your experience with anti-VEGF agents in your clinical practice? And how do you emulate or achieve the positive results that we saw in the clinical trials that seem to be elusive in the real world?
Joseph M. Coney, MD: We look at the trials and translate what that means in the everyday world, and it’s very difficult to do. We have learned a lot from our clinical trials, most importantly, that the people who get more injections do better. We did a study, Protocol I, which came out before Protocol T, and they looked at different things. At that time the gold standard was laser [therapy], and they were trying to see how the VEGF agents we had, which is ranibizumab, which was the only therapy we had—actually at that time, ranibizumab wasn’t approved for DME, because we were using a different dose in Protocol I, so there was no approved agent for DME—but they looked at ranibizumab with differed or prompt laser and compared it to triamcinolone, which is another way we tried to get rid of chronic swelling compared to laser alone.
They looked at safety and efficacy in the study, and the primary outcome was at 1 year, we were looking at the best mean change of visual acuity. Part of that study was an ad hoc analysis, which we learned a lot from. They looked at the 2 arms in the study that received ranibizumab, and these individuals received monthly injections, and the primary end point was at 1 year, but it was continued for 3 years. They wanted to see if there was a correlation between early treatment response and long-term visual gains. They defined early treatment response by the first 3 monthly injections, which is the first 12 weeks, and wanted to see how they did at week 52, which is 1 year, and this is carried on. They were very clever in how they did this, they broke them down into 3 different groups. The groups were those that had significant vision gains, which is more than 10 letters; those that did poorly, which is less than 5 letters; and those in the middle, between 5 and 9 letters. They found that individuals who received 3 injections in the first 3 months typically did about the same as they did at 1 year, and this was still extrapolated to years 2 and 3, we called it stayed in their swimming lanes. It is true that if you take those who did not do very well and you continue to inject those eyes, about a third of them will improve over time. The problem is that you’re giving monthly injections for an infinite amount of time, and two-thirds of those eyes are not getting better.
The majority of us have some type of end point where we think that we need to switch to a different agent. In Ohio, we’re forced to use off-label drugs, it’s how the insurance companies work, before we can go to a branded drug. We typically move that goal post earlier, and Protocol T taught me a lot of things, one being that after the first 3 injections, if I’m not getting the response that I want, I need to start thinking about something else. That end point to me is the OCT [optical coherence tomography]. The OCT is the one biomarker that we have to show a response to the therapy, because visual acuity is always subjective. After that third or fourth injection typically I’m switching within the same class, but with a different drug, but I’m also moving the goal post earlier in terms of an anti-inflammatory agent, or at least I’m starting to have that discussion with the patient. The way to buy equity with a patient is to show them how they have improved. Even when they don’t improve, there’s always some improvement we can show from where they start with their baseline OCT and where they are in 6 or 7 months. As long as OCT is coming down, the patient understands why they need to come back. It’s also important to start laying the foundation on when you want to start to change their therapy and the reason why. Some of our longer biologics have more adverse effects, and these are things that we can talk about. We must start talking about the potential adverse effects and complications that we get from longer biologics because the reason we cannot get to some of these end points is because the treatments we have now are short-lived. We need longer biologics because today we have no way of looking at a baseline OCT or a baseline examination and knowing who would or wouldn’t do well with any particular treatment.
Nancy Holekamp, MD: Thanks to all of you for this rich and informative discussion, and thank you for watching this HCPLive® Peer Exchange. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming Peer Exchanges and other great content right in your inbox.
Transcript edited for clarity.