This article was originally published in a sponsored newsletter.

We are approaching 1 year since pegcetacoplan (Syfovre; Apellis Pharmaceuticals) and avacincaptad pegol (Izervay; Iveric Bio/Astellas) were approved for the treatment of geographic atrophy (GA) secondary to dry AMD. Now that we have increased understanding and adoption of these therapies, it is time to tackle real-world practice and workflow questions.

Practice Patterns

I typically initiate pegcetacoplan therapy on the worse-seeing eye, in case patients have an episode of retinal vasculitis, even though that is rare.¹ Patients return for bilateral dilated exams at 1 week and 1 month to check for inflammation or signs of retinal vasculitis. Assuming all is well and the fellow eye also needs therapy, I treat the fellow eye and recheck with bilateral dilated exams in 1 week and again at 1 month. I typically keep patients on every-other-month injections because of the better safety profile noted with this frequency.² I offer bilateral therapy at each subsequent visit should patients desire it. I do not require dilation at every visit, but I do check for inflammation at the slit lamp, and I have a low threshold to dilate if any concerns arise.

When initiating avacincaptad pegol therapy, I also start with the worse-seeing eye. However, instead of a bilateral dilated check after 1 week, I bring patients back after 1 month. If there are no problems and the fellow eye also needs therapy, I initiate bilateral therapy and offer bilateral monthly therapy after. My dilation and inflammation monitoring stay the same as pegcetacoplan therapy.

My reasoning for less frequent checks with avacincaptad pegol therapy is based on its better safety profile. Treatment to date has shown no episodes of retinal vasculitis when therapy has been given on-label and only 1 case of inflammation in GATHER1/2.³ However, more real-world experience with avacincaptad pegol is needed to monitor for inflammation. For patients who have difficulty with the treatment burden of monthly injections, I offer injections every 6 to 8 weeks from initiation of therapy, with the caveat that it is an off-label dosing regimen.

Patient Flow Issues

Each patient who initiates therapy adds a substantial number of visits to the schedule, adding to the already large number of patients that we see as retina specialists. Many other factors also compound the complexity of these patients. First, the initial visit is often long and detailed because of the time needed to counsel these patients regarding the risks and benefits of therapy. This initial visit typically involves reviewing imaging and exam findings, discussing therapies, and ensuring that patients understand that neither of these therapies reverses the damage from GA. Patients must also understand the risks of therapy and the importance of compliance. I try to involve family members in the decision-making process, which can add time especially if a family member needs to be called after clinic.

Another time-consuming task is drawing up the medications, but we must do so meticulously because it is still not clear what causes episodes of retinal vasculitis with pegcetacoplan (ie, drug vs injection technique). Many patients who receive both pegcetacoplan and avacincaptad pegol will also have transient loss of vision after injection because of the 0.1 mL volume of the drugs. While this loss resolves without intervention in most, it keeps patients in the exam room for longer, which also interrupts patient flow.

Each patient requires optical coherence tomography (OCT) imaging at each visit to monitor for conversion to wet AMD, and the entire macula needs to be examined with OCT to check for occult choroidal neovascularization. If a patient converts to wet AMD, injections can become more complicated. It can be an administrative and logistical burden to keep track of the schedule of anti-VEGF and anti-complement injections, including co-pay assistance programs and benefits investigations. There can also be significantly increased patient burdens if injections are administered on separate days, but the injection code may not be reimbursed in full if an anti-VEGF and an anti-complement are given on the same day, and they may not be reimbursed if different drugs are given less than 28 days apart.⁴ It is important to keep track of injection intervals, paid claims, and reimbursement, which may take extra time.

Summary

There is no question that treatment of patients with GA adds an additional layer of complexity to clinics. However, patient flow issues will become more streamlined, and reimbursement issues will become less common in time. We will also understand the therapies better to devise regimented treatment algorithms that are tailored to disease severity. For now, both pegcetacoplan and avacincaptad pegol represent the only FDA-approved therapies for the treatment of GA, and our patients need to know about them to make an educated decision about whether they would like to try them.

References

1. Witkin AJ, Jaffe GJ, Srivastava SK, Davis JL, Kim JE. Retinal vasculitis after intravitreal pegcetacoplan: report from the ASRS Research and Safety in Therapeutics (ReST) Committee. J Vitreoretin Dis. 2023 Dec;8(1):9-20. doi:10.1177/24741264231220224
2. Heier JS, Lad EM, Holz FG, et al. Pegcetacoplan for the treatment of geographic atrophy secondary to age-related macular degeneration (OAKS and DERBY): two multicentre, randomised, double-masked, sham-controlled, phase 3 trials. Lancet. 2023;402(10411):1434-1448. doi:10.1016/s0140-6736(23)01520-9
3. Khanani AM, Patel SS, Staurenghi G, et al. Efficacy and safety of avacincaptad pegol in patients with geographic atrophy (GATHER2): 12-month results from a randomised, double-masked, phase 3 trial. Lancet. 2023;402(10411):1449-1458. doi:10.1016/S0140-6736(23)01583-0
4. Woodke J. Prepare your practice for GA reimbursement. Retina Today. Accessed February 28, 2024.

Priya Vakharia, MD is a member of Vit Buckle Society, the AAO, and the American Society of Retina Specialists. She practices at Retina Vitreous Associates of Florida in Palm Harbor and St. Petersburg.