Advancements in the Management of Macular Edema following Retinal Vein Occlusion - Episode 6

Macular Edema Following Retinal Vein Occlusion: Comparing Anti-VEGF Therapies

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Experts consider when they would use specific VEGF inhibitors for patients with macular edema following retinal vein occlusion.


Jayanth Sridhar, MD: How about comparing agents for you? I don’t think anyone knows more about the LEAVO study, for example, than you. That’s one of the trials we have that’s comparing agents head-to-head. How do you look at the data and interpret them and decide, which of these agents, between my off-label bevacizumab option and my on-label ranibizumab or aflibercept options, how do I weigh the pros and cons of each of these agents?

Rishi P. Singh, MD: LEAVO was a great study to look at the comparative effectiveness of head-to-head drugs for the treatment of retinal vein occlusion. This was CRVO [central retinal vein occlusion], and this study found that there were slight imbalances in final visual acuity in favor of aflibercept and ranibizumab in comparison to bevacizumab for the treatment of retinal vein occlusion. In addition, they found that more people on LEAVO had 15-line gains as result of receiving aflibercept. And with regard to the final acuity outcome, this was considered a noninferiority trial design, and essentially bevacizumab came out not noninferior to aflibercept and to ranibizumab, meaning that it was lesser as an agent, bevacizumab to both aflibercept and ranibizumab. Ranibizumab, while it was not the drug that was the winner in all cases, it was equivalent to aflibercept in many ways. Again, the only difference being the final visual acuity outcome, which favored aflibercept by 2 or 3 letters compared to ranibizumab. Overall it was a nice reaffirmation that all these anti-VEGF therapies are working quite well. But the important concept about LEAVO is that when you’re trying to compare these agents and you’re trying to look at what is the most effective, we know that aflibercept in this case was the most effective agent with regard to drying effect, final acuity, and 3 lines of improvement. If it was my eye, I would say I want to do aflibercept, knowing that this is an expensive drug, and we must be cautious about it. I’m not sure if you have any other interpretation of LEAVO, and then we can talk about some other studies as well.

Jayanth Sridhar, MD: That’s a great summary. A common question I get from colleagues or from trainees is, a 2- or 3-letter difference, what does that mean? That’s a small difference in the real world, but I agree with you. If you’re thinking all else being equal, if I had to pick between these 2 very similar options that are very efficacious, maybe I pick the one that, at least in the study, there was a difference that was picked up, and a study that was powered for that difference. How do you interpret that in the context of SCORE2? So SCORE2, a different trial, now we are looking at bevacizumab and aflibercept. SCORE2 was not a noninferiority trial in the same sense, and it did not show that visual acuity difference when you look at the early results, but there were some anatomic differences. How you tie those 2 results together if you want to talk more about SCORE2?

Rishi P. Singh, MD: SCORE2 does a good job of comparing aflibercept and bevacizumab, but the problem is SCORE2 is not a protocol we use in clinical practice. That was monthly injections for the first 6 months, and I don’t know about you, but I might give 1 or 2 injections, look at the OCT [optical coherence tomography] response, and then start to do either PRN [as needed], or a treat-and-extend regimen, depending on the patient’s desire. I don’t think I would have gone out as they did in SCORE2 as far as the treatment pattern goes. LEAVO on the other hand, the drug was given on an as-needed basis until they hit a threshold of retinal thickness and showed some differences there.

Again, the results from these studies are important to understand because both SCORE2 with head-to-head studies and LEAVO with a head-to-head trial, get maybe put together as equivalent. There are some major differences in these 2 studies, even though they might look equivalent from the design perspective. SCORE2 had patients with much older vein occlusions enrolled versus LEAVO had young fresh vein occlusions enrolled. Their chance of entry was around 30 to 45 days in LEAVO versus an almost 6-month period in SCORE2. That might have led to some imbalances with regard to final acuity outcome. Obviously, LEAVO showed a benefit in aflibercept, but SCORE2 showed an equivalence. That’s difficult because the drugs to us look different sometimes, they act differently sometimes, and we wonder if there was a difference. LEAVO tends to highlight what I see in clinical practice versus SCORE2 is not necessarily relatable to what I am seeing.

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Transcript edited for clarity.