A Treat-and-Extend Regimen of Intravitreal Brolucizumab for Exudative Age-Related Macular Degeneration Refractory to Aflibercept: A 12-Month Result

Abstract

We aimed to investigate whether a treat-and-extend regimen of intravitreal brolucizumab (6.0 mg/0.05 mL) is effective for eyes with exudative age-related macular degeneration (AMD) refractory to aflibercept for 12 months. Sixty eyes from 56 patients receiving brolucizumab for exudative AMD refractory to aflibercept were included. Patients received a mean of 30.1 aflibercept administrations for a mean 67.9-month follow-up. All patients exhibited exudation on optical coherence tomography (OCT) despite regular 4–8 weeks of aflibercept administration. Visit 1 was scheduled at the same interval from the last aflibercept injection to the baseline. The treatment interval was extended or shortened by 1–2 weeks depending on the presence or absence of exudation on OCT. After switching to brolucizumab, the follow-up interval significantly extended at 12 months (before switching: 7.6 ± 3.8 weeks vs. at 12 months: 12.1 ± 6.2 weeks, p = 1.3 × 10−7). Forty-three percent of the eyes achieved a dry macula at 12 months after switching. However, the best-corrected visual acuity did not improve at any visit. Morphologically, the central retinal thickness and subfoveal choroidal thickness significantly decreased from baseline at 12 months (p = 3.6 × 10−3 and 1.0 × 10−3, respectively). Switching to brolucizumab can be considered to extend the treatment interval in eyes with exudative AMD refractory to aflibercept.

The Effect of a Loading Dose Regimen in the Switch to Brolucizumab for Patients with Aflibercept-Resistant nAMD

“…The present study revealed that switching from aflibercept to brolucizumab with and without the loading dose regimen was effective in controlling retinal exudate in nAMD patients who had IRF and/or SRF under aflibercept administration at 8-week intervals. These results are consistent with previous findings in anti-VEGF treatment-resistant nAMD patients [ 12 , 13 ]. Kikushima et al reported the one-year results of switching to brolucizumab in nAMD patients who had retinal fluid after 4–8 weeks of aflibercept administration.…”

“…In the present study, the loading and nonloading groups had no visual improvement despite anatomical improvement. Improvements in anatomical outcomes without visual improvement have been reported in switching to another anti-VEGF drug [ 12 , 13 , 21 ]. We speculate that this discrepancy was due to permanent damage to photoreceptors caused by long-term disease activity and treatment.…”

“…Aflibercept [ 8 ], widely used as an anti-VEGF agent for nAMD, is usually administered at 8-16-week intervals [ 9 ], though approximately 30% of nAMD patients treated with aflibercept require 4- or 6-week treatment intervals [ 10 , 11 ]. Recent studies have shown the efficacy of switching to intravitreal injection of brolucizumab (IVBr) for patients with nAMD refractory to aflibercept [ 12 , 13 ]. When nAMD patients switch anti-VEGF agents, three monthly intravitreal injections as a loading dose regimen are recommended to start, though the administration interval that had been used before switching is sometimes continued in clinical practice.…”

Evaluating initial responses to brolucizumab in patients undergoing conventional anti-VEGF therapy for diabetic macular edema: a retrospective, single-center, observational study

“…Two clinical trials for DME, KESTREL and KITE, showed non-inferiority of brolucizumab to aflibercept in terms of visual outcomes, with more study participants achieving central macular thickness (CMT) < 280 µm 11 . Although favorable real-world results of switching to brolucizumab have been reported for age-related macular degeneration in patients previously treated with anti-VEGF therapy 12 , 13 , those for DME are not available. In addition, safety signals for brolucizumab in age-related macular degeneration (AMD) have been reported in RCTs and post hoc analyses, including intraocular inflammation (IOI) and retinal vasculitis with or without vessel occlusion 14 – 17 .…”

Evaluating initial responses to brolucizumab in patients undergoing conventional anti- VEGF therapy for diabetic macular edema: A retrospective, single-center, observational study

“…Two clinical trials for DME, KESTREL and KITE, showed non-inferiority of brolucizumab to a ibercept in terms of visual outcome, with more number of study participants achieving central macular thickness (CMT) < 280 µm [11]. Although favorable real-world results of switching to brolucizumab have been reported for age-related macular degeneration in patients previously treated with anti-VEGF therapy [12,13], those for DME are not available. In addition, safety signals for brolucizumab in age-related macular degeneration (AMD) have been reported in RCTs and post hoc analyses, including intraocular in ammation (IOI) and retinal vasculitis with or without vessel occlusion [14][15][16][17].…”