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Response after three anti-VEGF injections predictive of long-term outcomes in DME, analysis shows
Visual acuity findings need to be backed up by OCT data, but the evidence produced will have a significant impact on clinical practice.
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A post hoc analysis of Diabetic Retinopathy Clinical Research Network data showed that the long-term response to anti-VEGF treatment of diabetic macular edema can be assessed after three injections.
The Early Anti-VEGF Response and Long-term Efficacy (EARLY) analysis was based on the DRCR.net Protocol I study, a 3-year phase 3 multicenter trial that included 854 eyes of 691 patients.
“We looked at VA after three injections at 3 months of follow-up and found that this outcome can be predictive of final visual acuity. In other words, patients who gained less than five letters after 3 months had very little chance of gaining more vision at 1 or 3 years,” OSN Europe Edition Board Member Anat Loewenstein, MD, said.
The cohorts were defined as gaining less than five letters, between five and nine letters, and 10 or more letters. After multivariate adjustment, a significant correlation remained between best corrected visual acuity gain at week 12 and years 1 and 3.
“Only one out of three patients gaining less than five letters at 3 months gained more at later time points of the follow-up,” Loewenstein told Ocular Surgery News. “From this we conclude that if a patient does not respond after three injections, it might make sense to consider switching to a steroid.”
Impact on clinical practice
The findings of the EARLY analysis will significantly affect clinical practice, according to Albert J. Augustin, MD.
“Now we know we can judge after three injections if the patient is a non-responder, a moderate responder or a good responder, and in case of low-moderate or insufficient response, we can switch to an alternative agent such as a steroid or another anti-VEGF drug. I have recommended for a long time that we should switch as soon as possible and not continue injecting insufficiently responding patients, but now we have the scientific evidence,” he said.
Based on EARLY results, more than 40% of patients might benefit from switching to a different therapy, which is a large number that has a potential positive impact of reducing the burden on patients and the system.
“Most of the pivotal trials looked at least at five to six injections, and most of us in the U.S. and Europe try at least six injections before deciding to switch. In this regard, this may be a game changer because there are data showing that if a patient does not respond at all it does not make sense to continue injecting the same drug. I think that from now on, those of us who used to do many injections even if the patient did not respond at all will consider switching earlier,” Loewenstein said.
The fact that one out of three patients still improves after a negative result at 3 months suggests, however, that these conclusions cannot be generalized. Both specialists agreed that a personalized approach to the individual patient is still required.
OCT findings
“We are soon going to publish our findings, and I am convinced that the community will react to these really impressive data. The DRCR.net Protocol I is an independent study. Allergan only conducted the post hoc analysis of the data, and this makes the conclusions even more robust,” Augustin said.
EARLY’s conclusions now need to be backed up by OCT findings because OCT, more than visual acuity, is used as a parameter for treatment decisions, Loewenstein said.
“We do have a preliminary analysis of OCT data, which seem to be consistent with VA parameters,” she said. “We are also looking at the area under the curve, and from this we are gaining additional important information.”
“We can gather a lot more information than just retinal thickness from OCT. Some of these data, such as integrity of the photoreceptor outer segment and of the IS/OS junction, might help us draw a better correlation between VA and OCT and should be further investigated,” Augustin said.
Similar studies could also help set criteria for non-responders to anti-VEGF therapy in age-related macular degeneration patients and help establish when to switch between anti-VEGF agents.
“Unlike in DME, there is no proven alternative to anti-VEGFs for AMD. However, some patients improve when switched to aflibercept,” Loewenstein said.
“Also in AMD, the earlier we can predict long-term efficacy and switch in between drugs, the better,” Augustin said. “Since we know that inflammation plays a significant role in AMD, we may even want to add an anti-inflammatory drug in some cases.”
Earlier detection of an insufficient response to anti-VEGFs will be a positive step in view of the introduction of new therapies currently under research. – by Michela Cimberle
- For more information:
- Albert J. Augustin, MD, can be reached at the Department of Ophthalmology, Klinikum Karlsruhe, Moltkestrasse 90, 76133 Karlsruhe, Germany; email: albertjaugustin@googlemail.com.
- Anat Loewenstein, MD, can be reached at Tel Aviv Sourasky Medical Center, Department of Ophthalmology, 6 Weizmann St., Tel Aviv, Israel 64239; email: anatl@tlvmc.gov.il.
Disclosures: Augustin reports he receives speaker honorarium and travel expenses from Allergan. Loewenstein reports she is a consultant for Allergan, Alcon, Bayer, Notal Vision and Novartis.