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By now, the groundbreaking results of the NEI-sponsored CATT study are well known in the ophthalmic community. The one-year results of this head-to-head study comparing the effectiveness of Genentech’s two anti- VEGF drugs, bevacizumab (Avastin) and ranibizumab (Lucentis), showed equivalent visual results in patients with wet AMD on the same intravitreal dosing schedule of either drug.1
But for many clinicians, questions remain on how best to incorporate these findings into their own practice. EyeNet asked three vitreoretinal subspecialists about the lessons that they believe the CATT study holds for everyday clinical practice. These experts are Donald S. Fong, MD, MPH, director of clinical trials research for Kaiser Permanente in Pasadena, Calif.; Philip J. Rosenfeld, MD, PhD, professor of ophthalmology at the University of Miami (Dr. Rosenfeld wrote an editorial that accompanied the study results2); and Adrienne Williams Scott, MD, assistant professor of ophthalmology at Johns Hopkins University in Baltimore.
Lucentis or Avastin?
EyeNet: How will the conclusions from CATT affect your choice of intravitreal anti-VEGF therapy?
Dr. Scott: I believe that the results reinforce what many of us in the vitreoretinal community have been seeing in our practices. I have a good mix of patients on either drug. I spend about 40 percent of my time at a satellite clinic where only Avastin is available. For my patients, the choice between Avastin or Lucentis is often location driven, determined by the patient’s willingness to travel to the main hospital for Lucentis, the FDAapproved therapy.
I will continue to offer patients a choice between the two drugs, reminding them that, while we know both drugs work well, there are still unanswered questions regarding the longterm safety profile of each.
Dr. Rosenfeld: I like the idea that Medicare covers both drugs and that the choice can be made by me and the patient. My patients decide which drug they would like administered based on their insurance coverage, their financial picture and their comfort level with off-label therapy.
However, if I have a patient who, for some reason, needs to come in less frequently for injections, I now know from CATT that a pure as-needed dosing regimen, which is more common internationally than it is in the United States, is effective with Lucentis. I’m sure it’s also effective with Avastin, but vigilance is required on the part of the patient and the clinician, whichever drug is chosen. [Editor’s note: For Avastin, the study showed equivalence between monthly and as-needed regimens at 36 weeks but statistically inconclusive results at 52 weeks.]
Dr. Fong: In my opinion, at this point there’s no reason to use Lucentis.
Some of us had concerns that using Avastin was somehow inferior and might harm our patients. Now, the decision is easy because CATT shows that there really is no difference in clinical outcomes between these drugs.
I work for a large, group-model HMO, and based on several years of experience with both drugs, we were confident of their equivalence. But individual physicians make the decisions within our system. Some of my colleagues who had previously used Avastin switched to Lucentis after it was approved by the FDA. I switched for a while, too, but I couldn’t see any clinical difference.
Health care financing is a zero-sum game, so I think that our system will be coming out with a regional policy, with some very strong guidelines saying, “You really shouldn’t be using Lucentis.” The money we save in that way can be spent elsewhere in the system. I think this is a real victory for cost containment.
What Do You Tell Your Patients?
EyeNet: How do the CATT results affect the way you talk to patients?
Dr. Rosenfeld: I am continuing to give my patients a summary of everything we know about the effectiveness and safety of these two drugs. I tell them that only one of them has FDA approval but that a randomized, controlled clinical trial confirmed that monthly Avastin is as effective as Lucentis at protecting their vision.
Dr. Scott: After CATT was released, most of my Avastin patients came in on their next visit with copies of articles that reported the drugs’ equivalence. They clearly feel more comfortable with using the drug off label now that it has been studied in the larger, randomized clinical trial.
I give my new patients the results of the CATT trial and tell them that, when administered every four weeks, both drugs are equivalent. But I say that we still have some unanswered questions, that we don’t know what the serious systemic events are going to be long term. Finally, I weigh their insurance status and how comfortable they are being treated with an off-label drug when an FDA-approved drug is available.
Dr. Fong: Safety is always an issue, but so far there has not been a huge signal about this. Our own experience in our HMO patients does not seem to bear out any apparent additional risk of stroke, and biologically, it doesn’t really make sense that there would be.
So I say to my patients, “We aren’t sure. But we’re giving you a very small dose of Avastin, and it’s unlikely to even make it outside the eye, past the blood-retina barrier.” And when they ask me what I would do for a member of my own family, I tell them that I would be comfortable using Avastin.
OCT or FA?
EyeNet: In light of CATT, how are you monitoring therapeutic effect—with optical coherence tomography (OCT) or fluorescein angiography (FA)?
Dr. Rosenfeld: FA was the gold standard in evaluating wet AMD for many years. But it appears that OCT is the new proven gold standard. As used in CATT, OCT was more sensitive than FA in identifying a treatment effect.
This was the first large, prospective, randomized study that looked at the two clinical imaging modalities side by side. It demonstrated that OCT clearly is superior. It is also easier to use, and it’s noninvasive. In my patients, I do FA at baseline, but there is very little reason to use angiography in the course of their management.
I’m starting to think that it may also be unnecessary for patients who are injected at every visit to get an OCT each time. If I’m performing injections every four to six weeks in a patient who has been shown to require chronic therapy, I may only need to perform OCT quarterly. Then, if I don’t image them every time, I may be able to get patients in and out within an hour. So far I’ve tried this in only two patients, but I’m thinking of expanding this strategy to other patients.
Dr. Fong: I order only a handful of angiograms a year. It’s not just a matter of money and resources, either. The patients don’t like FA. Switching to OCT is a real patient pleaser.
We give our patients with apparent exudative AMD a choice: FA or a trial of Avastin injections. Most opt for skipping the angiogram. Then we monitor with OCT, to see that the fluid is going down.
Dr. Scott: It depends on the patient and on the CNV lesion. I don’t image every Avastin or Lucentis patient at every single treatment visit. But I probably get an OCT for about 80 percent so that I can follow the response to treatment. You also can show patients their OCTs so they can see that their retina is improving. Many times, this encourages the patient and the accompanying family member that we are making progress.
EyeNet: What unanswered questions do you have about these two drugs?
Dr. Fong: The main question I have now is how infrequently you can give the injections. Because if you could get away with treating every six or eight weeks, that would be a huge boon for the patients, for the health care system and for our patient load.
Dr. Rosenfeld: Between monthly dosing and pure as-needed dosing there is a hybrid strategy, called treat and extend. You give an injection at every visit and gradually extend the interval between visits, but only if the macula remains dry. The idea is that you treat the patient every time, but the longer gaps between visits reduce the total number of injections over the course of a year. And you still maintain a dry macula this way.
In Norway, there is an ongoing clinical trial of treat and extend [for both Lucentis and Avastin], but the results won’t be reported until next year.
Dr. Scott: My lingering question now is this: Is there a true difference in the serious systemic events between the two drugs? The CATT trial was not powered to detect these differences.
1 Martin, D. F. et al. N Engl J Med 2011;364(20):1897–1908.
2 Rosenfeld, P. J. N Engl J Med 2011;364(20):1966–1967.
Drs. Fong, Rosenfeld and Scott report no financial conf licts of interest.