Considerations for Switching Diabetic Macular Edema Treatments

Nancy Holekamp, MD: Dr Cohen, I’m glad that you talked about that post-hoc analysis of Protocol I because it tells you in the real world that not everybody does well with anti-VEGF agents. It’s important we initiate therapy to monitor and ensure that the patient is responding maximally, and if they’re not, then we don’t want to continue a therapy that’s not matched or fit for that patient, and we should switch to another agent or to a different class of drugs. Dr Leng, can you discuss under what circumstances you would switch agents and what biomarkers you use, the OCT [optical coherence tomography], vision? how many injections do you use before you assess whether a patient’s responding optimally?

Theodore Leng, MD, FACS: There are many different indications for switching. Certainly, a worsening in vision on the current therapy would be a reason to consider switching them to a new agent. As a specialty, most people would say give 3 monthly injections, and if you’re not seeing an adequate response that would be a good time to switch. The OCTs are what you use to make that determination. If we do not see the response to the OCT that we’d expect, meaning resolution of inter-retinal fluid and subretinal fluid in a reasonable manner with each subsequent injection, then it might be that the agent we’ve chosen needs to be switched to something different. Sometimes you can figure that out after 2 injections, and sometimes you might want to give the full 3 before you contemplate trying a different agent.

Nancy Holekamp, MD: Dr Rahimy, what‘s your approach to determining responders versus poor responders, and switching agents and different classes of drugs?

Ehsan Rahimy, MD: I learned a lot too from that Protocol I secondary analysis, it’s a great study, the early study that Dr Cohen mentioned. For those who think about a potential criticism of that group that did not gain much vision, it’s easy to look at it and say they were all poor responders, but somebody could look at it and say, maybe some of those patients had great vision to begin with because they could get into a trial with 20/30, 20/25 vision, so maybe that’s overweighting it. The investigators in that study smartly accounted for that, they did a secondary analysis where they eliminated patients who had good starting vision and only looked at patients who could still improve. They were essentially getting rid of a ceiling effect, and they still showed, Dr Cohen’s point, that people still stayed in their lane. That was eye-opening for me as well.

We are more and more entertaining the thought of switching earlier in the treatment course. I’m reminded of, at least when I was in training, the big studies my mentors would pass on and impart to me were the RISE and RIDE studies. RISE and RIDE were landmark clinical trials that looked at ranibizumab, which is Lucentis, and its indication was for DME [diabetic macular edema]. If you look at the visual acuity curves in RISE and RIDE, it’s a little different than some of the other anti-VEGF curves we see because with RISE and RIDE, it’s an initial ascent, and it almost looks like patients are still gradually improving all the way across. I remember my mentors telling me, “Just keep hammering, just keep hammering, and eventually they’ll catch up, eventually they’ll catch up.” Dr Cohen mentioned that point earlier. We know that a portion of those patients do catch up, but does that mean you give monthly injections to everybody? What is the cost of that in terms of treatment burden to patients, to society, and those other two-thirds in the Protocol I study who maybe benefited from something else, and could have gotten vision back had it been switched earlier?

That pendulum in our field is switching toward being more aggressive. If you do not see a great response early within the first couple of injections, colleagues will say anywhere between 3 and 6 injections, they consider switching, if they are on off-label Avastin [bevacizumab] to either aflibercept or Lucentis, and then to the other one. Or in my case, I’m already incorporating a corticosteroid at that point to try to use synergistic therapy. In previous conversations it was always about switching. Do we just switch classes of medications? I look at the retina field and a lot of us think this way. Maybe we’re like the early days of oncology, we’re thinking about combination therapy. That’s ideally where we want to head, especially with something as challenging as diabetic retinopathy. This isn’t a this or that, we need to utilize all the tools in our toolbox; that may be laser [therapy], anti-VEGF, steroids, and we haven’t even talked about surgery. Surgery ends up being an option for these patients as well. If I don’t see a good response early on, that could be based on the OCT as well as the vision, then I like to add a steroid, continue with their treatment, and assess how they’re doing.

Nancy Holekamp, MD: I’m gleaning some very key concepts here. One is an initiation phase where monthly injections are given with close monitoring to identify the responders versus the nonresponders who may need to switch to a different agent or even to a different class.

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.