Patients with neovascular AMD who experience rapid fluid resolution with aflibercept 8 mg maintain long-term dosing intervals
Michael Stewart, MD, of the Mayo Clinic in Jacksonville, Florida, talks about data presented at the 2025 ARVO meeting that showed the presence or absence of fluid at week 4 was a very significant determinant of how well patients could be extended in the long-term for those treated with aflibercept.
Michael Stewart, MD:
I’m discussing a presentation that was given at ARVO in 2025, and this was a post-hoc analysis of data from the PULSAR trial. PULSAR was the phase 3 registration trial for aflibercept 8 mg, and it was structured where the patients with new-onset neovascular age-related macular degeneration were randomized at baseline to receive aflibercept 8 mg Q12, aflibercept 8 mg Q16, or aflibercept 2 mg Q8, all of which were given after 3 monthly loading doses.
Patients then in the 8-mg groups were evaluated several locations during the first year, and depending upon how they did with respect to visual acuity and central retinal thickness, they were either maintained on the Q12 or Q16 regimen through the first year, or they had their intervals shortened by 4-week adjustments if they failed to meet the DRM criteria. Now, during the second year of the trial, there was also an opportunity for extension and patients could be extended if their visual acuity was stable. Stable means less than 5 letters of vision loss relative to where they were at week 12 and if they had no intra or subretinal fluid in the central subfield.
During the second year, there was eligibility to extend out to Q24 if they met all of their criteria. Well, the question that we posed was, does early drying of the macula, and by early we mean at 4 weeks, 8 weeks, and 12 weeks into the trial, does the presence or absence of intra- or subretinal fluid during that time period, does that influence how well they’re able to be extended at week 96? Are patients who are drier, can they get extended longer? Do patients who have persistent fluid, are they less likely to be extended?
We went back and looked at the data and for each patient at weeks 4, 8, to 12 weeks, we said, “Is there fluid present or absent?” We broke it down into 5 different sub cohorts. One was absence of fluid at week 4, and it didn’t matter what 8 and 12 were. The second was absence of fluid at 4 and 8, 12 didn’t matter. Then absence of fluid at 4, 8, and 12. Then on the other side, the flip side of that was presence of fluid. The first was presence of fluid at week 4, but absent fluid at week 8, meaning the patient then dried after the second injection. Then the second cohort was presence of fluid at 4, 8, and 12, a patient that never dried during the induction phase. Then that was then looked and correlated with how they did in terms of their last achievable interval at week 96. Was it 8, 12, 16, 20, or 24 weeks?
What we found, not surprisingly, was those patients that dried quickly, and by quickly we mean at week 4, they’re the ones that were most likely to see extended intervals at the end of week 96. Interestingly, it didn’t seem to matter if they were dry at 4 and wet at 8 or dry at 4, at 8, and wet at 12, as long as they were dry at 4, then their extendability at week 96 was almost identical.
In those patients who had no fluid at week 4, about 53% of them were at weeks 20 or 24 on the extended intervals at the end of the second year. On the other side of that, what about the patients who had persistent fluid at week 4? Well, whether they had persistent fluid at week 4 and were dry at 8, or they had persistent fluid 4, 8, and 12, they performed fairly comparably at weeks 96. Not surprisingly, those patients who had persistent fluid at week four, they did not see the same extended intervals at week 96, as did those patients that were dry at week 4.
There wasn’t a whole lot of difference between fluid at 4 and dry at 8 or fluid at 4, 8, and 12. Though in this post-hoc analysis, we did not do a quantitative analysis because of the post-hoc nature of this. There were fairly comparable results between those 2 groups. The bottom line is those patients who were dry at week 4 had the ability to be extended to longer intervals at week 96. Those patients who were wet at week 4 did not have the same success in reaching long-term intervals at the week 96.
In PULSAR, the presence or absence of fluid at week 4 was a very significant determinant of how well patients could be extended in the long-term.
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