Expert explores efficacy of Eylea in weaning patients off wet AMD treatment
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Investigators retrospectively analyzed visual and anatomic outcomes of patients who were attempted to be weaned off wet age-related macular degeneration therapy with either off-label intravitreal Avastin or intravitreal Eylea.
Patients in both arms received three monthly loading doses of each drug followed by a treat-and-extend protocol, with extension intervals dictated by clinical metrics including OCT findings. Eyes of patients that were extended to at least 12 weeks were then given the opportunity to have a pause in their ongoing treat-and-extend protocol (ie, a cessation in their injections) but were still followed by quarterly monitoring visits to determine whether additional treatment might be necessary again.
The authors found the two study cohorts to have similar visual acuity results at the end of 1 year of treatment, but not surprisingly, the 52 patients in the Avastin (bevacizumab, Genentech) group received more injections on average (8.7 ± 0.3) compared with the 70 patients in the Eylea (aflibercept, Regeneron) arm (7.2 ± 0.3).
However, despite receiving fewer injections, eyes of patients in the Eylea arm were three times more likely to be weaned off treatment (43% vs. 15%) compared with eyes of patients receiving Avastin. Tantalizingly, albeit in this small, uncontrolled, open-label, retrospective study, the authors also showed that this benefit of being able to wean off AMD therapy favoring Eylea persisted through even 2 years (52% vs. 27%).
Unfortunately, the way the data are presented, we cannot discern how many of the 43% of Eylea patients who were able to wean off therapy at 1 year were still a part of the 52% of similar patients at 2 years. That is to say, how many of those 43% of Eylea patients at 1 year were still without additional treatment at 2 years?
The authors also found additional benefits favoring the Eylea arm. One specific benefit was that, at the 1-year time point, it was observed that 61% of eyes of patients in the Eylea group had no fluid on OCT compared with just 39% of those in the Avastin group. Insofar as OCT is such an important decision-making tool for retina specialists, this difference is robust, clinically meaningful and practically relevant.
In addition to the aforementioned methodological limitations of the study design, another limitation of this study was the selection bias regarding the initial choice of Avastin vs. Eylea. The initial choice of drug was left up to the patient after a detailed description of each medication was provided by the treating physician. The authors have previously reported that many patients choose Avastin over Eylea and justified that decision on the basis of altruism (ie, acknowledging that there are societal benefits of opting for the more cost-effective drug over the more efficacious drug) when doing so.
Another form of bias that has to be considered in this open-label study was that the decision to extend or pause therapy may have been influenced by the treating physician’s own preconceived notions of each drug’s potency, overall effectiveness and, most importantly, durability. In other words, the investigators may have been more likely to pause therapy in a patient known to be receiving Eylea (compared with Avastin) and more likely to continue a more rigorous dosing algorithm in a patient known to be receiving Avastin (compared with Eylea).
One aspect of the study methodology that surprised me was the mandate for three initial monthly loading doses of each drug. If one’s goal is to reduce the number of injections overall (and potentially stop them altogether), why require all patients to receive three initial monthly injections in a mandated fashion? We know from the as-needed arms of the CATT study that three monthly loading doses are not required to realize positive visual outcomes in patients with wet AMD. Many patients likely could have been immediately “extended” after a robust drying effect was noted just 1 month after the first injection. Along those lines, it would have even been more interesting to see the difference in treatment burden between the two drugs if that initial dosing algorithm would have been employed instead of mandating the three monthly loading doses.
Even though precipitous drops in vision were not appreciated in this study after long periods without drug exposure, it remains, at least in my mind, a potential concern when weaning patients off wet AMD therapy. This was a relatively small study with relatively short follow-up (following the pause in therapy), so it is possible that a larger study with longer follow-up may have uncovered some deleterious anatomic and functional outcomes in patients foregoing therapy for prolonged periods. Patients in this study were only followed quarterly following the pause but may have benefited from more frequent in-office monitoring to mitigate the risk of missing a clinical deterioration in the interim.
All that said, the objective data presented in this study are still quite compelling and suggest what a lot of us feel we already know: There are many advantages of Eylea over Avastin in the management of wet AMD, while the one glaring disadvantage is simply cost. Indeed, the authors describe the collective clinical benefits favoring Eylea in the present study as “a previously unappreciated advantage” of Eylea over Avastin, which may come as a surprise to the legions of retina specialists who have used both drugs for this ubiquitous condition and have already come to appreciate these differences the authors so nicely demonstrated in their publication.
References:
- Cao X, et al. J Clin Invest. 2022;doi:10.1172/JCI159125.
- CATT Research Group, et al. N Engl J Med. 2011;doi:10.1056/NEJMoa1102673.
- Malik D, et al. JAMA Netw Open. 2021;doi:10.1001/jamanetworkopen.2020.37880.
For more information:
Andrew A. Moshfeghi, MD, MBA, can be reached at Maloney-Shamie Vision Institute, 10921 Wilshire Blvd., Suite 900, Los Angeles, CA 90024; email: moshfega@med.usc.edu.
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