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Once-monthly aflibercept benefits patients with early persistent fluid
Eyes that have early persistent fluid and received monthly aflibercept gained more lines of vision than those that received ranibizumab every 4 weeks or aflibercept every 8 weeks.
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Intravitreal injections of aflibercept every 4 weeks after monthly injections may provide an additional benefit to patients with early persistent fluid from neovascular age-related macular degeneration, a study found.
In a post hoc analysis of the VIEW1 and VIEW2 studies, the authors compared Eylea (aflibercept, Regeneron) 2 mg every 4 weeks to aflibercept 2 mg every 8 weeks and Lucentis (ranibizumab, Genentech) 0.5 mg every 4 weeks in eyes that had early persistent fluid.
“It was the [eyes] that were in the every 4 week aflibercept group that had the best visual acuity compared to the other two groups, so we seem to have identified a group of patients who benefited from monthly treatment over that first year,” corresponding author Glenn J. Jaffe, MD, told Ocular Surgery News. “The way that we currently treat patients, in the real world, it’s unusual for people to get monthly treatment over an extended time period. It’s unusual for a variety of reasons. One is because it’s harder on the patient, and two, it’s harder on the physician, so often a compromise is reached.”
Dosing regimens
The analysis, published in Ophthalmology, included 1,815 eyes with known fluid status at baseline and 4, 8 and 12 weeks. Patients were randomized to one of three treatment groups: ranibizumab 0.5 mg every 4 weeks (595 patients), aflibercept 2 mg every 4 weeks (613 patients) or aflibercept 2 mg every 8 weeks (607 patients) after three monthly injections.
Primary outcome measures were mean change in best corrected visual acuity from baseline over weeks 16 to 52 and the percentage of eyes that gained 15 letters or more or lost five letters or more. Visual outcomes were assessed in eyes with and without persistent intraretinal or subretinal fluid.
The analysis focused on data through 52 weeks because the dosing regimen in all treatment arms changed to as-needed from 52 weeks to 96 weeks. Thus, the 52- to 96-week period was not included.
Visual acuity in eyes with early persistent fluid was not an endpoint in the original VIEW1 and VIEW2 studies, Jaffe said.
Treatment effect
Early persistent fluid was seen on each of the first three office visits after baseline in 29.4% of eyes in the 4-week ranibizumab group, 18.8% of eyes in the 4-week aflibercept group and 20.3% of eyes in the 8-week aflibercept group.
Retinal fluid status fluctuated in all three groups, but greater fluctuation was seen in the 8-week aflibercept group and 4-week ranibizumab group. The average proportion of visits without retinal fluid was 57.4% in the 4-week ranibizumab group, 75.1% in the 4-week aflibercept group and 57.9% in the 8-week aflibercept group.
Mean gains in visual acuity at 52 weeks were 11.7 letters in the 4-week aflibercept group, 8.5 letters in the 4-week ranibizumab group and 7.5 letters in the 8-week aflibercept group. The difference between the 4-week aflibercept group and 4-week ranibizumab group was statistically significant (P < .01), as was the difference between the 4-week aflibercept group and the 8-week aflibercept group (P < .05).
Also at 52 weeks, 33.7% of eyes in the 4-week ranibizumab group, 35.2% of eyes in the 4-week aflibercept group and 31.5% of eyes in the 8-week aflibercept group gained 15 or more letters.
Visual acuity outcomes did not depend on the type of early persistent fluid, intraretinal or subretinal, Jaffe said.
“In eyes without early persistent fluid, the visual acuities at 1 year were similar, regardless of whether you treat with aflibercept every 4 weeks or 8 weeks or ranibizumab every 4 weeks. However, in the 20% of eyes with early persistent fluid regardless of whether the fluid is intraretinal or subretinal, if you have that persistent fluid early on, people tend to do better when they’re treated with monthly aflibercept. These data were suggestive that you should treat with monthly treatment if you have early persistent fluid, regardless of whether the fluid was intraretinal or subretinal.
“The study we reported was a post hoc analysis. To definitively prove that you should start monthly when there is early persistent fluid, you’d actually have to do the study starting prospectively where you’re going to treat patients with either of these three regimens monthly for the first three visits, and then you base your treatment following that on whether or not they have early persistent fluid. That hasn’t been done yet, and that would be the definitive proof,” Jaffe said.
The reason for better visual outcomes in the 4-week aflibercept group among eyes with persistent fluid is not known. However, the authors hypothesized that treatment-naïve eyes that are less sensitive to anti-VEGF anti-permeability effects may require continuous anti-VEGF treatment to forestall the adverse effects of fluid on photoreceptors and other structures. – by Matt Hasson
- Reference:
- Jaffe GJ, et al. Ophthalmology. 2016;doi:10.1016/j.ophtha.2016.05.016.
- For more information:
- Glenn J. Jaffe, MD, can be reached at Duke Ophthalmology, 2351 Erwin Road, Durham, NC 27705; email: jaffe001@mc.duke.edu.
Disclosure: Jaffe reports he has served as a consultant for Alcon, Genentech and Neurotech.
Perspective
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Seenu M. Hariprasad, MD
In treating the neovascular AMD patient, we are faced with two scenarios after three initial monthly Eylea or Lucentis injections either those who have a dry macula or those who are not dry (early persistent fluid).
VIEW 1 and VIEW 2 showed us that in all patients, visual outcomes were similar across groups regardless of fluid status at 3 months. However, Jaffe and colleagues showed that in the subset of patients with early persistent fluid, Eylea dosed monthly may provide additional clinical benefit than either Eylea dosed every 8 weeks or Lucentis dosed monthly.
The need to increase frequency of anti-VEGF dosing in patients not responding rapidly is not a new concept. In 2012, I published a paper comparing fixed monthly vs. less frequent dosing of Lucentis and found that although some patients have rapid improvements in visual acuity, others do not experience peak visual acuity until later during treatment. In my study, continued monthly dosing of Lucentis resulted in a greater percentage of patients gaining more than 15 letters than with switching to less frequent dosing regimens.
The current study is a very useful, practical study that adds to the body of knowledge for managing patients who have persistent fluid after 3 monthly injections of anti-VEGF. The message is simple: If response is not adequate, increase anti-VEGF dosing frequency.
Reference: Hariprasad SM, et al. J Ophthalmol. 2012;doi:10.1155/2012/690641.
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