Early Experience With Brolucizumab Treatment of Neovascular Age-Related Macular Degeneration

Abstract

IMPORTANCEOutcome data are limited regarding early experience with brolucizumab, the most recently approved anti-vascular endothelial growth factor (VEGF) agent for the treatment of neovascular age-related macular degeneration (nAMD).OBJECTIVE To report clinical outcomes after intravitreous injection (IVI) of brolucizumab, 6 mg, for nAMD. DESIGN, SETTING, AND PARTICIPANTSThis retrospective case series conducted at 15 private or academic ophthalmological centers in the United States included all consecutive patients with eyes treated with brolucizumab by 6 retina specialists between October 17, 2019, and April 1, 2020. EXPOSURES Treatment with brolucizumab IVI, 6 mg. MAIN OUTCOMES AND MEASURES Change in mean visual acuity (VA) and optical coherence tomography parameters, including mean central subfield thickness and presence or absence of subretinal and/or intraretinal fluid. Secondary outcomes included ocular and systemic safety. RESULTS A total of 172 eyes from 152 patients (87 women [57.2%]; mean [SD] age, 80.0 [8.0] years) were included. Most eyes (166 [96.5%]) were not treatment naive, and 65.7% of these eyes (109 of 166) were switched from the prior anti-VEGF agent because of persistent fluid detected on optical coherence tomography scans. Study eyes received a mean (SD) of 1.46 (0.62) brolucizumab IVIs. The mean (SD) VA prior to starting brolucizumab was a 64.1 (15.9) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score (Snellen equivalent, 20/50) and was a 63.3 (17.2) ETDRS letter score (Snellen equivalent, 20/63) at the last study evaluation (mean difference, 0.8; 95% CI, −2.7 to 4.3; P = .65). When analyzed by number of brolucizumab IVIs, the presence or absence of fluid prior to starting brolucizumab, or the presence or absence of intraocular inflammation after receiving brolucizumab, there was no difference in mean VA prior to starting brolucizumab compared with after brolucizumab IVIs or at the final study evaluation. The mean (SD) central subfield thickness in all eyes prior to starting brolucizumab was 296.7 (88.0) μm and was 269.8 (66.5) μm at the last study examination (mean difference, 26.9 μm; 95% CI, 9.0-44.7 μm; P = .003). Intraocular inflammation was reported in 14 eyes (8.1%) and was self-limited and resolved without treatment in almost half those eyes (n = 6). One previously reported eye (0.6%) had occlusive retinal vasculitis and severe loss of vision. CONCLUSIONS AND RELEVANCEIn this analysis of brolucizumab IVI for nAMD, VA remained stable, with a reduction in central subfield thickness. Intraocular inflammation events ranged from mild with spontaneous resolution to severe occlusive retinal vasculitis in 1 eye.

Brolucizumab in Neovascular Age-Related Macular Degeneration – Indian Real-World Experience: The BRAILLE Study

“… 7 In the real-world, the SWIFT trial found that 12.4% of 207 IVI brolucizumab patients had IOI, while Enriquez et al found that 8.1% of the 172 eyes studied had IOI. 15 In our series of 126 brolucizumab injections, however, we found no cases of IOI. The etiopathogenesis of brolucizumab-induced inflammation remains undetermined, although efforts are currently underway to explore the same.…”

“…13,14 In a comparable study, Enriquez et al found no significant visual improvement in 166 eyes undergoing switch therapy and 6 treatment-naive eyes with nAMD. 15 The lack of significant improvement in BCVA among the treatment-naive eyes was intriguing to note in our investigation, despite a positive trend toward visual gains. In contrast, Bilgic et al observed that brolucizumab improved vision in both treatment-naive and switch therapy eyes with nAMD.…”

“…The SHIFT trial, as well as Enriquez et al, have shown similar improvements in CST. 13,15 Complete resolutions of SRF, IRF, and PED were observed in 15.5%, 39.29%, and 23.81% of our study eyes. In comparison, the SRF resolution in the BREW trial was superior (39.4%), while the PED resolution was suboptimal (6.4%).…”

“…In contrast, the usage of brolucizumab has been associated with visual threatening occlusive vasculitis. 15 , 21 In fact, the American Society of Retina Specialists (ASRS) released an alert on February 23 and March 30, 2020, inflammatory issues with the brolucizumab molecule. 22 In the post-marketing surveillance, the incidence of retinal vasculitis +/retinal vascular occlusion has been 15.4 per 10,000 injections (till July 8, 2021).…”

“… 23 The fact that these inflammatory events were observed in the Caucasian population is important to highlight from the clinical trials and real-world data. 15 , 21 Our real-world study, on the other hand, assessed the safety and efficacy in an Indian population, ie, Southeast Asians. Racial and genetic differences in the occurrence of systemic and ocular inflammation have been widely reported.…”