Brolucizumab, Alternating Anti-VEGFs Extends nAMD Treatment Intervals

Joseph M. Coney, MD

Credit: American Society of Retina Specialists

Switching to brolucizumab alone or brolucizimab with alternating anti-vascular endothelial growth factor (VEGF) agents were each linked to extended injection intervals, preserved vision, and reduced central macular thickness (CMT) among eyes with neovascular age-related macular degeneration (nAMD).¹

According to the real-world data, the mean injection intervals could be extended more than twice as much in those treated with brolucizumab alone (3.8 weeks) compared to those treated with brolucizumab alternating with another anti-VEGF agent (1.6 weeks) at month 12. The trend continued at month 18, with injection interval extensions of 5.2 weeks and 2.0 weeks, respectively.

“Our data suggests that both anti-VEGF treatment regimens can preserve vision, reduce central macular thickness, and extend anti-VEGF intervals in patients with nAMD, which increases the treatment options for patients with nAMD,” wrote the investigative team, led by Joseph M. Coney, Retina Associates of Cleveland Inc.

Intravitreal anti-VEGF agents are the standard of care in nAMD treatment and have led to a substantial decrease in visual impairment due to retinal diseases.² However, despite these benefits, the maintenance of visual gains requires frequent anti-VEGF injections, creating a treatment burden for both patients and their healthcare providers. Treatment regimens, including pro re nata and treat-and-extend, are considered less burdensome, but maintenance of vision is long-term and delays in treatment due to noncompliance broadens the risk of avoidable vision loss.

Many patients continue to exhibit suboptimal response despite frequent anti-VEGF injections and as a result, may be switched to another anti-VEGF agent to better their chance of improved treatment outcomes. Optimization of a treatment regimen for a patient with nAMD may both improve and stabilize their visual outcomes but also minimize the burden faced during treatment.¹

In this retrospective study, Coney and colleagues evaluated visual acuity, anti-VEGF injection intervals, and CMT among a real-world population with nAMD treated with either brolucizumab alone or with brolucizumab alternating with other anti-VEGF agents. The non-interventional cohort study was performed at a large retina practice between October 2019 and November 2021.

The brolucizumab cohort included patients who switched from a previous anti-VEGF, were previously analyzed, and had ≥3 brolucizumab injections with no other agent in the first 12 months of follow-up. The alternating cohort included patients who switched from another agent to brolucizumab and had ≥2 brolucizumab injections and ≥1 injection of another agent in the same period. For the 18-month analysis, eyes in the brolucizumab cohort received no agent other than brolucizumab, while there were no restrictions on the anti-VEGF used after month 12 in eyes in the alternating cohort.

Among 414 patients, 482 eyes received ≥1 brolucizumab injection during the study period. At month 12, the mean visual acuity changes from baseline were –1.1 ± 15.1 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in the brolucizumab cohort (n = 174) and 1.3 ± 13.0 letters in the alternating cohort (n = 47). At month 18, the visual acuity changes were 0.0 ± 13.5 ETDRS letters in the brolucizumab cohort and by –7.3 ± 17.2 letters in the alternating cohort.

At baseline, the mean injection intervals were noted as longer in the brolucizumab cohort (6.8 weeks) than in the alternating cohort (4.6 weeks). At month 12, injection intervals were extended by nearly 26.9 days (3.8 weeks) in the brolucizumab cohort, compared with 11.1 days (1.6 weeks) in the alternating cohort. In the 18-month results, intervals were extended by 36.3 days (5.2 weeks) in the brolucizumab cohort and 14.0 days (2.0 weeks) in the alternating cohort.

Regarding mean changes in CMT, the data showed a change of –35.2 ± 108.1 µm in the brolucizumab cohort and –31.5 ± 91.2 µm in the alternating cohort at month 12. At month 18, CMT reductions were –38.9 ± 75.0 µm in the brolucizumab cohort and –9.0 ± 59.9 µm in the alternating cohort.

Given the urgent safety measures of intraocular inflammation introduced following the MERLIN study in June 2021, investigators noted the recommendation was made that brolucizumab should not be administered more frequently than every 8 weeks after the 3 monthly loading doses.³ As a result, however, Coney and colleagues indicated the alternating treatment regimen may allow more flexibility to optimize disease management and reduce treatment burden.¹

“However, this study has demonstrated that alternating treatment between brolucizumab and other anti-VEGF agents when injection intervals ≤8 weeks are required allows physicians more flexibility to balance optimal disease activity management and minimization of the anti-VEGF injection burden by resuming brolucizumab injections once the patient no longer requires injections more frequent than every 8 weeks,” investigators wrote.

References

1. _{Coney JM, McCoy JE, Buxy Sinha S, et al. One-Year and 18-Month Outcomes in nAMD Patient Eyes Switched to Brolucizumab Alone versus to Brolucizumab Alternating with Other Anti-VEGF Agents. Clin Ophthalmol. 2023;17:3601-3611. Published 2023 Nov 23. doi:10.2147/OPTH.S432957}
2. _{Ricci F, Bandello F, Navarra P, Staurenghi G, Stumpp M, Zarbin Z. Neovascular age-related macular degeneration: therapeutic management and new-upcoming approaches. Int J Mol Sci. 2020;21(21). doi:10.3390/ijms21218242}
3. _{Khanani AM, Brown DM, Jaffe GJ, et al. MERLIN: phase 3a, multicenter, randomized, double-masked trial of brolucizumab in participants with nAMD and persistent retinal fluid. Ophthalmology. 2022;129(9):974–985. doi:10.1016/j.ophtha.2022.04.028}