Optimizing Anti-VEGF Treatment Outcomes in Neovascular AMD and DME - Episode 4

Real-World Long-Term Safety Data of Anti-VEGF Agents

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Experts discuss safety data of anti-vascular endothelial growth factor (Anti-VEGF) agents while highlighting the importance of sharing this information with patients and relevant care providers.


Ehsan Rahimy, MD: Considering patients with these retinal diseases need regular injections for a long time, the safety of these medications we use daily is obviously critical. What can you tell us about the real-world long-term safety data available for VEGF therapies?

Ali Khan, MD, FACS, FASRS: We divide this question into ocular adverse events vs systemic. The main thing we all worry about is endophthalmitis. Luckily, the injection risk for endophthalmitis is quite low. A 1 in 10,000 risk is what I tell my patients. With Betadine [povidone-iodine] and perhaps additional masking, that number has gone down. I tell patients that with any procedure there’s a risk of infection, but luckily it’s quite low.

Most patients, at least in my discussions, are worried about systemic adverse effects. Cardiovascular events, such as stroke, and even all-causes mortality have been brought up with anti-VEGF injections. Some early studies looked at an increased risk of these cardiovascular events, including stroke and all-causes mortality, with anti-VEGFinjections, but we have large data sets that support that these medications are quite safe.

Some recent studies came out. One had about 60,000 patients with diabetes, and it compared patients who got anti-VEGF injections vs those who got steroid or laser for diabetic treatment. It found that their cardiovascular event rate and everything was similar. That spoke to me: even for patients who had diabetes but don’t get anti-VEGF, the cardiovascular risk profile was similar to those who did get frequent anti-VEGF. That was reassuring.

Another study looked at all-causes mortality and found that the frequency of injections that patients were getting did not affect their all-causes mortality rate. That was supportive. Even patients who are getting these monthly had no change in risk for all-causes mortality than those who got it less frequently. More and more, we’re seeing that these medications are safe. Obviously, if a patient recently had a stroke or a heart attack, many of us would pause to go over that risk of stroke and cardiovascular events because we don’t think the medications significantly increase your risk. But that’s the discussion that comes up more often. Luckily, these larger studies are giving us some reassurance that there’s not a significant increased risk.

Ehsan Rahimy, MD: Where are the rest of you with this? You get a patient with AMD [age-related macular degeneration]. They’re at risk for stroke, or patients with diabetes are at risk for MI [myocardial infarction] or stroke. Are you stopping therapy? Observing switching therapy? What are you doing these days? The conversations changed over the years. The pendulum swung. Most colleagues say they continue to treat. What do you do?

Jonathan Jonisch, MD: We’re fortunate to have multiple meta-analyses, a large number of well-done phase 3 clinical trials highlighting the safety of these drugs. We’ve been using them at a high volume for over 20 years, without any study highlighting a statistically significant rise in systemic events. The question arises when a patient has had a recent event. When you’re talking about risk, all these patients are at high risk. We have patients with diabetes and senior citizens. Those are the prime patients who are going to get strokes and heart attacks. All the patients are at risk. A question comes up for patients on therapy who had a recent event, whether it’s an MI or a stroke: what do we do with them? For the most part, the data show that the risk benefit supports continuing treatment when there are no other alternatives.

In patients with diabetic macular edema, we have treatments like corticosteroids that may allow you to skip, although I’m not sure that’s evidence based in terms of causing or worsening the disease. The experience with these drugs given intravenously obviously raises those risks. We extrapolate that to the intravitreal injection, but I’m not sure that’s evidence based. Most of us do that. If there’s an option, it makes sense. In most cases, the risk of not treating the eye probably outweighs the risks of those events.

Veeral Sheth, MD, MBA, FASRS, FACS: I agree with Jon’s approach. When you say that to a patient and you offer them the option of hitting pause on a treatment, especially our patients with AMD, they elect to continue. A lot of patients will tell you, and I’m sure all of you have heard this in clinic, “I’d rather be dead than blind.” It’s a real fear for patients to lose their vision, and it motivates them to continue with treatment.

The other thing is that the data that Ali brought up are important for us to know and brush up on, because there’s a lot more direct-to-consumer marketing happening. I’m sure you’ve had patients come in recently [saying], “What drug are you giving me? I’ve seen this new commercial.” The more we see that, and the more they mention some of the adverse effects and things like that on these commercials, the more questions we’re going to get. A cardiologist recently asked me about some of these things. And so it’s going to become something we talk about a little more, knowing that data and understanding and reassuring patients is going to be important.

Ehsan Rahimy, MD: Veeral, that’s an awesome point. We’re seeing an uptick of this conversation across the board. It’s not just from patients but also from family members and other doctors who take care of them. We’ve all seen the pharmaceutical commercials with the voiceover that starts blurting out 200 things that can happen to you in 5 seconds. I’m having to answer this multiple times. It’s a very relevant point that we’re talking about.

Transcript edited for clarity.