ABSTRACT
Management of vitreoretinal disorders (e.g., neovascular age-related macular degeneration [nAMD] and diabetic macular edema [DME]) have assumed the standard therapy of lifelong anti-VEGF injections with drugs like aflibercept, brolucizumab, ranibizumab and bevacizumab. However, the burden imposed on patients is a major deterrent for continual therapy and recovery. Faricimab, a bispecific antibody, blocking both VEGF-A and Ang-2 molecules, produces a comparable functional and anatomical results, with less injections, significantly reducing patient burden. Visual acuity, safety, adverse effects, and anatomical outcomes are discussed in the pivotal clinical trials (YOSEMITE/RHINE and TENAYA/LUCERNE), and early data from real-world studies (TRUCKEE, TAHOE, FARWIDE-DME, FARETINA and others). In YOSEMITE and RHINE, faricimab demonstrated non-inferior vision gains, better anatomical outcomes compared to aflibercept every 8 weeks. Faricimab in the personalized treatment interval (PTI), after week 96, achieved 12-week interval in 78.1% of the patients and 16-week interval in 62.3%. TENAYA and LUCERNE reported comparable best corrected visual acuity (BCVA) improvement and better anatomic outcomes during head-to-head phase, parallel to aflibercept, at its 8-week treatment schedule. Faricimab in the PTI regimen, after week 96 achieved 12-week interval in 77.8% of the patients and 16-week interval in 63.1%. Safety of faricimab has been comparable to aflibercept in these pivotal trials. Real-world data supports the data from the pivotal studies regarding the efficacy and safety profile of faricimab in heterogenous real world patient population. Moreover, in previously treated patients, it also demonstrated a faster fluid resolution, good safety profile. Considering faricimab has demonstrated anatomic and durability benefit in the treatment of nAMD and DME, additional data from ongoing extension clinical trials, AVONELLE-X and RHONE-X will help understand longer term outcomes for patients treated with faricimab as well as patients switching from aflibercept to faricimab after finishing the pivotal trials. Longer term data from the real-world studies will also continue to contribute to our understanding of long-term efficacy, safety and durability in the real world patient population.
ABSTRACT
Purpose: To evaluate real-world experience using intravitreal brolucizumab (IVBr), alone or in combination with aflibercept, in eyes with neovascular age-related macular degeneration (nAMD) treated previously with other inhibitors of VEGF (anti-VEGF). Methods: This was a retrospective study of all eyes with nAMD treated with IVBr on a treat-and-extend protocol at a single center. Best-corrected visual acuity (BCVA), optical coherence tomography (OCT) at baseline and final visit, and drug-related adverse events were analyzed. Eyes with recurrent macular fluid on IVBr every 8 weeks were treated with a combination therapy alternating between IVBr and aflibercept every month. Results: Among 52 eyes (40 patients) on IVBr, all had been previously treated with other anti-VEGF therapy, with 73% having persistent macular fluid. After a mean follow-up of 46.2±27.4 weeks on IVBr, the mean treatment interval for intravitreal therapy increased to 8.8±2.1 weeks on IVBr from a baseline of 6.1±3.1 weeks (p<0.001). Macular fluid decreased and BCVA was stable/improved in 61.5% of eyes on IVBr. Ten eyes with increased macular fluid on IVBr monotherapy when extended to every 8 weeks were treated with combination therapy alternating between IVBr and aflibercept every 4 weeks. In these eyes, 80% had improved macular fluid on OCT and 70% stable or improved BCVA after a median follow-up of 53 weeks on combination therapy. Mild intraocular inflammation developed in four eyes, all occurring on IVBr monotherapy, and none had associated vision loss. Conclusion: In the real world, IVBr used to treat eyes with nAMD previously treated with other anti-VEGF therapies appears to be well tolerated and associated with an improvement in macular fluid, stabilization of BCVA, and/or increase in intravitreal treatment interval. Combination therapy alternating between IVBr and aflibercept monthly appears to be well tolerated and can be considered for eyes with macular fluid on IVBr every 8 weeks.
