Meeting News CoveragePerspective

Experts explore protocols for switching anti-VEGFs

WAILEA, Hawaii – There is little evidence published to help guide clinicians in making the decision to switch from one anti-VEGF therapy to another. Panelists at a round table that focused on the treatment of wet age-related macular degeneration addressed that topic at Retina 2015.

Pravin U.
Dugel

“I look at the glide path to dryness,” Philip J. Rosenfeld, MD, PhD,said. “I anticipate it’s going to look better with each sequential monthly injection. You can make the argument that there are those ‘late gainers’ [of improvement], but most patients improve with those first few monthly doses. When I don’t see that glide path improving, I switch.”

Looking at a case scenario in which a non-responder had undergone 13 injections of the same anti-VEGF, Neil M. Bressler, MD, said that he would switch treatment for anyone with worsening.

“A person should continue to improve until they have no activity. If they stop improving, I’ll do one more [injection] and say, ‘Well, maybe I’m just not analyzing it’ or ‘There’s some biological variability,’ but after two injections of not improving, then you want to consider that you have the ability to switch,” Bressler said.

Evidence to support a protocol of when to switch is sparse, Bressler said. Additionally, time is a confounder.

“People switch, but they also have additional treatments, and had they continued with the same treatment over time, they might have seen the same benefit. And, again, they show benefits anatomically and not in visual acuity. So, I do think it’s worthwhile if they’re worsening. If someone’s no longer improving, why not try another agent that’s been shown to work?”

Bressler said, in a case of long-term anti-VEGF treatment – 24 treatments – a dramatic change 1 month after a switch in therapy is unlikely to be due to the additional time of therapy.

“First thing I would do is make sure that it’s a VEGF-driven disease,” Pravin U. Dugel, MD, said. This is where you want to get a fluorescein angiogram, possibly an ICG, but the other thing I would do here is go ahead and give an anti-VEGF, then see the patient in a week or two to see if it’s actually a VEGF-driven disease. Once you’ve established that, then I think it’s reasonable to consider switching.” – by Patricia Nale

Disclosures: Bressler reports that his institution does contracted research for Bayer, Genentech, Lumenis, Novartis and Regeneron. Dugel reports receiving consultant fees from Alcon, Allergan, Genentech and Thrombogenics. Rosenfeld reports doing contracted research for Acucela, Advanced Cell Technology, Carl Zeiss Meditec, Genentech and GlaxoSmithKline; receiving consultant fees from Acucela, Alcon, Alexion, Allergan, Boehringer Ingelheim, Chengdu Kanghong Biotech, Genentech, Healios KK, Oraya, F. Hoffmann-La Roche and Vision Medicine; and having ownership interest in Digisight.

WAILEA, Hawaii – There is little evidence published to help guide clinicians in making the decision to switch from one anti-VEGF therapy to another. Panelists at a round table that focused on the treatment of wet age-related macular degeneration addressed that topic at Retina 2015.

Pravin U.
Dugel

“I look at the glide path to dryness,” Philip J. Rosenfeld, MD, PhD,said. “I anticipate it’s going to look better with each sequential monthly injection. You can make the argument that there are those ‘late gainers’ [of improvement], but most patients improve with those first few monthly doses. When I don’t see that glide path improving, I switch.”

Looking at a case scenario in which a non-responder had undergone 13 injections of the same anti-VEGF, Neil M. Bressler, MD, said that he would switch treatment for anyone with worsening.

“A person should continue to improve until they have no activity. If they stop improving, I’ll do one more [injection] and say, ‘Well, maybe I’m just not analyzing it’ or ‘There’s some biological variability,’ but after two injections of not improving, then you want to consider that you have the ability to switch,” Bressler said.

Evidence to support a protocol of when to switch is sparse, Bressler said. Additionally, time is a confounder.

“People switch, but they also have additional treatments, and had they continued with the same treatment over time, they might have seen the same benefit. And, again, they show benefits anatomically and not in visual acuity. So, I do think it’s worthwhile if they’re worsening. If someone’s no longer improving, why not try another agent that’s been shown to work?”

Bressler said, in a case of long-term anti-VEGF treatment – 24 treatments – a dramatic change 1 month after a switch in therapy is unlikely to be due to the additional time of therapy.

“First thing I would do is make sure that it’s a VEGF-driven disease,” Pravin U. Dugel, MD, said. This is where you want to get a fluorescein angiogram, possibly an ICG, but the other thing I would do here is go ahead and give an anti-VEGF, then see the patient in a week or two to see if it’s actually a VEGF-driven disease. Once you’ve established that, then I think it’s reasonable to consider switching.” – by Patricia Nale

Disclosures: Bressler reports that his institution does contracted research for Bayer, Genentech, Lumenis, Novartis and Regeneron. Dugel reports receiving consultant fees from Alcon, Allergan, Genentech and Thrombogenics. Rosenfeld reports doing contracted research for Acucela, Advanced Cell Technology, Carl Zeiss Meditec, Genentech and GlaxoSmithKline; receiving consultant fees from Acucela, Alcon, Alexion, Allergan, Boehringer Ingelheim, Chengdu Kanghong Biotech, Genentech, Healios KK, Oraya, F. Hoffmann-La Roche and Vision Medicine; and having ownership interest in Digisight.

    Perspective

    There are no large randomized trials that switch half the patients and show that switching actually is indicated, but it is reasonable to switch some patients at some time. What we do not know is which patients, when to switch, what drug to switch to and if the switch actually helps. Dr. Dugel points out that some patients are not responding because they won’t respond; the diagnosis is wrong. They actually have a simulating condition so step one is to reconsider the diagnosis. For me, step two is to review the past treatment. Have there been missed visits or skipped injections? If so, maybe stay the course but treat monthly for a while? Because we do not know which drug is better, if the patient asks to switch, I am happy to do so. Keep in mind that even after a year of injections, most patients still have fluid; I tend to switch for worsening and not persistent fluid. As far as switching for vision, acuity may fluctuate month to month. Also, some vision decreases are not due to age-related macular degeneration. We are in the “art” phase of when to switch. As the science catches up, we can have more certainty that our decisions are evidence based.

    • MD, Andrew P. Schachat
    • Vice Chairman, Cole Eye Institute Cleveland

    Disclosures: Schachat is a consultant for AnGes.

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