Intravitreal therapies neutralizing vascular endothelial growth factor (VEGF) have considerably reduced the extent of vision loss in patients with neovascular age-related macular degeneration (nAMD). Nevertheless, there exist a number of limitations to anti-VEGF therapy, including the requirement of repetitive injections and inadequate response in a subset of subjects. As a consequence, novel treatments and delivery systems are being developed to target other complementary mediators implicated in angiogenesis. Faricimab (Vabysmo)is a bispecific antibody targeting VEGF-A and Angiopoietin-2 (Ang-2). Intravitreal faricimab (IVF) may be more efficacious to IVA in regards to allowing longer treatment intervals when employing an optical coherence tomography (OCT)-guided management protocol, In this study, the authors evaluated the short-term benefits of switching nAMD subjects from IVA to IVF when treatment-resistance is encountered using an OCT-guided management protocol in a real-world setting.
A retrospective review was conducted on nAMD patients undergoing IVA therapy at a single private practice institution. Subjects were divided into Study and Control groups. Both Study and Control subjects had undergone ≥6 IVA treatments during the previous 12 months, ≥4 IVA treatments during the previous 6 months, had a central macular thickness (CMT) on optical coherence tomography (OCT) of ≥300 microns, and had observable intraretinal and/or subretinal fluid on OCT prior to group assignment. Study subjects were switched from IVA to IVF and received 3 treatments within 4 months. Control subjects remained on IVA during the same time period and received 3 treatments within 4 months.
There were a total of 55 subjects analyzed. There were 39.3% (11/28) in the Study Group and 7.4% (2/27) in the Control Group attaining a CMT of less than 300 microns without retinal fluid on OCT at the end of the 4-month study period (p = 0.004). There were 35.7% (10/28) in the Study Group and 7.4% (2/27) in the Control Group gaining 2 or more lines of visual acuity at the end of the 4-month study period (p = 0.008).
Both visual and anatomic outcomes were improved in a clinically significant minority when subjects were switched to faricimab from aflibercept in cases of recalcitrant nAMD. This suggested that faricimab potentially offers fewer intravitreal injections without compromising long-term outcomes in this difficult-to-treat subgroup of treatment-resistant nAMD subjects when a treat-and-extend protocol is employed, as is the preference for a majority of vitreoretinal specialists. The authors considered this benefit clinically meaningful since 27.6–70.3% of subjects undergoing anti-VEGF therapy for nAMD have been reported to persist with intraretinal and/or subretinal fluid on OCT despite monthly injections and studies suggest that long-term visual outcomes are optimal when all residual retinal fluid is resolved. Fewer intravitreal injections with stable visual and anatomic outcomes in this elderly population may benefit the patient (fewer doctor visits), the specialist (more opportunity to see other vitreoretinal patients requiring attention), and society (lower overall cost to the payer).
In conclusion, switching nAMD subjects who are recalcitrant to aflibercept treatment to faricimab may result in better visual and anatomical outcomes in a statistically significant portion of subjects, thereby leading to potentially longer treatment intervals when a real-world treat-and-extend management protocol is followed. Further research is warranted to confirm these findings, especially with a longer follow up period.
Source: Rush and Rush; Clinical Ophthalmology 2022:16 https://doi.org/10.2147/OPTH.S395279
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