Current and Emerging Treatment Options for Age-Related Macular Degeneration - Episode 4

Anti-VEGF Agent Therapy Considerations for Patients With AMD

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Lloyd Clark, MD, and Jennifer I. Lim, MD, give their insight into therapy considerations when deciding to use anti-VEGF agents to treat age-related macular degeneration.

Karl Csaky, MD, PhD: Lloyd, say a patient comes in, we just heard Carl tell us that we have these agents. How do you go about making a decision, talking about any safety issues, anything in that initial discussion that goes through your mind in terms of, here are some guidelines for myself that I’ve established? Is there a rational way to choose what agent depending on if we have 3 agents that are available right now? Is there anything that you can share with us in terms of your own personal decision-making?

Lloyd Clark, MD: Oftentimes, it seems increasingly, year after year, this decision is made for us by external forces, and that can be challenging because that doesn’t always jibe with our clinical experience or our judgment in these situations. Putting that aside, the 2 most important factors for treatment are an initial response, getting the disease state under control as quickly and as completely as possible, meaning get the choroidal neovascularization, the exudation to stop, and to really inhibit all of the exudation in the eye. The second goal is to reduce treatment burden and be able to extend patients. I’m an aggressive treatment extender in clinical practice. Those 2 don’t necessarily add up when we think about the first goal in terms of rapid control of exudation in patients with exudative AMD [age-related macular degeneration].

We don’t have a lot of guidance in terms of level 1 evidence to support any agent. All the agents used monthly are effective in terms of treating patients with wet AMD. In the initial phase of treatment, I feel comfortable either making the decision or the decision being made for me in terms of what to use for a patient’s monthly therapy, as we’re starting treatment for wet AMD. The trick is that I don’t want to commit patients to monthly therapy forever, because we know from a number of prospective clinical trials as well as retrospective work, that a majority of patients, even with the agents that we have—set aside some of the newer agents that we’ll discuss later—but with the agents that we have, close to a majority, if not a small majority, can be managed as infrequently as every 12 weeks. That’s not the case with our off-label therapy with bevacizumab. We know from the CATT trial that treatment less than monthly is not as effective as treatment with the FDA-approved agents.

I tend to favor FDA-approved therapy for more chronic treatment because the data support these drugs because of their higher affinity and better effectiveness. I split this up into a 2-phase treatment, where the first phase doesn’t make a tremendous difference to me, but the evidence supports some differentiation as we treat patients more chronically.

Karl Csaky, MD, PhD: Jennifer, let’s talk about if you’ve got these patients in your clinic, you’re treating them, and they don’t respond. Let’s say vision wise, they don’t see an improvement. You see some improvement in their fluid, but it’s not dramatic. Do you quickly switch or do you continue to push those injections just waiting for things? What is your timetable in terms of what we would call early decision-making? As Lloyd was saying, he has this 2-pronged, 2-time frame approach. Tell us what’s going through your mind as you see your patients.

Jennifer I. Lim, MD: Right. Karl, it’s important that we give each agent the best shot at it, and in order to do that you have to load them and then see the response. There was a paper by I believe [Winfried] Amoaku, [MD,] and [Usha] Chakravarthy, [MD, PhD, CBE,] was on it, published in Eye. What they looked at was the early response and after you load the patient. Three loading doses, and you see them at month 4 and you see is there a response, did the vision improve, did the fluid go away? You would say good response is the fluid resolved, the visual acuity improved within 5 letters, because usually it doesn’t improve a lot more than that unfortunately in AMD, unless the vision is significantly dropped because of floor-and-ceiling effect.

When you look at that early group, what you would characterize as a poor responder then is somebody who had no response at all. That’s what you were saying, if the person had no response in the fluid, their vision didn’t improve, they stayed the same, would I stop? No, I would not stop. I would keep going because there are percentages of patients who early on don’t respond, but they’re later responders, and it doesn’t necessarily mean that you need to switch the drug.

I would push and I would go at least 5 times with that treatment, unless you were using a drug and now they’re developing a lot more fluid, the visual acuity is significantly dropping, and there’s subretinal hemorrhage, and you were using perhaps a drug that doesn’t have as good of a drying effect as Lloyd alluded to. Some of the branded drugs are known to dry up better and have been shown in clinical trials to have better drying effect in terms of intraretinal fluid and subretinal fluid, although the visual acuity necessarily didn’t change in the trial itself. In that situation, if I were using a nonbranded drug, I would switch to a drug that has a higher ability to dry the retina if I were seeing worsening fluid. All else being equal, I would give it a good try to go at least 5 shots with the agent.

This transcript has been edited for clarity.