Purpose: To describe 3 cases of intraocular inflammation (IOI) in patients who received faricimab and high-dose aflibercept in consecutive order. Methods: Retrospective case review. Results: Three patients, 2 with neovascular age-related macular degeneration (nAMD) and 1 with central retinal vein occlusion (CRVO), transitioned from 2 mg aflibercept to either faricimab (in cases 1 and 2) or high-dose aflibercept (in case 3) due to persistent disease activity. In all cases, contemporary medication provided minimal effect. Subsequently, patients in cases 1 and 2 were switched to high-dose aflibercept at their next visit, and the patient in case 3 was switched to faricimab. On follow-up, the disease worsened in all 3 cases. Each patient returned to their previous drug. Shortly after, each patient developed an episode of IOI. Conclusions: Patients receiving different high-dose or longer-acting agents in short order may be at risk for developing antidrug antibodies and IOI.
OhrMKaiserPK.Aflibercept in wet age-related macular degeneration: a perspective review. Ther Adv Chronic Dis. 2012;3(4):153-161. doi:10.1177/2040622312446007
2.
WykoffCCBrownDMReedK, et alEffect of high-dose intravitreal aflibercept, 8 mg, in patients with neovascular age-related macular degeneration: the phase 2 CANDELA randomized clinical trial. JAMA Ophthalmol. 2023;141(9):834-842. doi:10.1001/jamaophthalmol.2023.2421
3.
HeierJSKhananiAMQuezada RuizC, et alEfficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials. Lancet. 2022;399(10326):729-740. doi:10.1016/S0140-6736(22)00010-1
4.
LanzettaPKorobelnikJFHeierJS, et alIntravitreal aflibercept 8 mg in neovascular age-related macular degeneration (PULSAR): 48-week results from a randomised, double-masked, non-inferiority, phase 3 trial. Lancet. 2024;403(10432):1141-1152. doi:10.1016/S0140-6736(24)00063-1
5.
ThangamathesvaranLKongJBresslerSB, et alSevere intraocular inflammation following intravitreal faricimab [published correction appears in JAMA Ophthalmol. 2024 Apr 1;142(4):393. doi: 10.1001/jamaophthalmol.2024.0998] [published correction appears in JAMA Ophthalmol. 2024 Jun 1;142(6):588. doi: 10.1001/jamaophthalmol.2024.1965]. JAMA Ophthalmol. 2024;142(4):365-370. doi:10.1001/jamaophthalmol.2024.0530
6.
AndersonWJda CruzNFSLimaLHEmersonGGRodriguesEBMeloGB.Mechanisms of sterile inflammation after intravitreal injection of antiangiogenic drugs: a narrative review. Int J Retina Vitreous. 2021;7(1):37. doi:10.1186/s40942-021-00307-7
7.
AveryRLCastellarinAASteinleNC, et alSystemic pharmacokinetics and pharmacodynamics of intravitreal aflibercept, bevacizumab, and ranibizumab. Retina. 2017;37(10):1847-1858. doi:10.1097/IAE.0000000000001493
BayerP. A study to learn how well a higher amount of aflibercept given as an injection into the eye works and how safe it is in people with reduced vision due to swelling in the macula, central part of the retina caused by a blocked vein in the retina (Macula Edema Secondary to Retinal Vein Occlusion) (QUASAR). Clinicaltrials.gov. January6, 2025. Accessed February 1, 2025. https://classic.clinicaltrials.gov/ct2/show/NCT05850520
WitkinAJJaffeGJSrivastavaSKDavisJLKimJE.Retinal vasculitis after intravitreal pegcetacoplan: report from the ASRS Research and Safety in Therapeutics (ReST) Committee [published correction appears in J Vitreoretin Dis. 2024 Feb 29;8(3):363. doi: 10.1177/24741264241238212]. J Vitreoretin Dis. 2023;8(1):9-20. doi:10.1177/24741264231220224
13.
WitkinAJHahnPMurrayTG, et alBrolucizumab-associated intraocular inflammation in eyes without retinal vasculitis. J Vitreoretin Dis. 2021;5(4):326-332. doi:10.1177/2474126420975303
DiackCAveryRLCheungCMG, et alOcular pharmacodynamics of intravitreal faricimab in patients with neovascular age-related macular degeneration or diabetic macular edema. Transl Vis Sci Technol. 2024;13(11):13. doi:10.1167/tvst.13.11.13
16.
Food and Drug Administration, HHS. The clinical evaluation of Qt/QTc interval prolongation and . . . international conference on harmonisation of technical requirements for registration of pharmaceuticals for human use. 2005. Accessed February 2, 2025. https://database.ich.org/sites/default/files/E14_Guideline.pdf
17.
FDA. Guidance for industry: statistical approaches to establishing bioequivalence. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). 2001. Accessed February 2, 2025. https://www.fda.gov/downloads/drugs/guidances/ucm070244.pdf
18.
WileyHEThompsonDJBaileyC, et alA crossover design for comparative efficacy: a 36-week randomized trial of bevacizumab and ranibizumab for diabetic macular edema. Ophthalmology. 2016;123(4):841-849. doi:10.1016/j.ophtha.2015.11.021
19.
BrownDMChenEMarianiAMajorJCJr; SAVE Study Group. Super-dose anti-VEGF (SAVE) trial: 2.0 mg intravitreal ranibizumab for recalcitrant neovascular macular degeneration-primary end point. Ophthalmology. 2013;120(2):349-354. doi:10.1016/j.ophtha.2012.08.008
