A recent case series highlighted the potential for inflammation events following intravitreal injections of faricimab for the treatment of neovascular age-related macular degeneration.
The study, published in JAMA Ophthalmology, documents three cases of severe intraocular inflammation following treatment with faricimab. The cases were identified between September and October 2023 at three clinic locations of a single institution, prompting concerns over a potential increase in severe inflammation events associated with faricimab. The reported cases occurred from two different lot numbers.
While the incidence of retinal vasculitis with or without occlusion is rare—0.17/10,000 injections, according to updates in the U.S. prescribing information—the investigators of this severe intraocular inflammation (IOI) cluster were skeptical that the events were coincidental.
All patients experienced significant vision loss initially, with visual acuities dropping to hand motion or counting fingers in the affected eyes within 3-4 days post-injection. However, after prompt treatment, including vitreous taps, intravitreal antibiotics, and in one case, vitrectomy, inflammation resolved within one month. Vitreous taps in all cases were culture-negative, indicating sterile inflammation rather than infectious endophthalmitis. One case had a single colony of Staphylococcus epidermidis that was deemed a contaminant.
The investigators noted that these events might differ from the retinal occlusive IOI events that prompted updated prescribing information. “None of the patients in this current case series had signs of retinal arteritis or venulitis once the ocular media cleared,” they wrote in the article. “Their frequency, though, supports the possibility that rates of acute, severe IOI in clinical trials following faricimab might not accurately capture the clinical practice setting expectations of these events. The relatively small number of cases in this series precludes determining with confidence the true incidence of this complication at this time.”
The researchers suggested possible mechanisms for sterile IOI events, including patient susceptibility with antidrug antibodies, protein aggregates in the drug manufacturing process, or properties of the agent itself. Like all other anti-VEGF treatments, the researchers recommended continuing to weigh the risks and benefits with evidence from large registries or insurance databases when choosing agents to treat retinal diseases for individual patients.
Investigators in another case series, also published in JAMA Ophthalmology, agreed with this recommendation of vigilance after they reviewed 12 eyes from 7 patients with neovascular age-related macular degeneration and diabetic macular edema who were treated with intravitreal faricimab injections at a tertiary referral center in Switzerland between June 2022 and March 2024. Most patients in the study who developed IOI were treated with topical or systemic corticosteroids, which resolved the inflammation. However, two eyes developed retinal vasculitis, and one exhibited occlusive vasculitis which led to irreversible vision loss from 20/80 to 20/2000. Three eyes also experienced elevated intraocular pressure (≥30 mm Hg). Despite moderate anterior segment inflammation, most cases did not lead to substantial vision changes. All patients had previously received other anti-VEGF therapies like aflibercept or ranibizumab before switching to faricimab.
The investigators in these new cases noted that their “data are consistent with available case series and clinical practice setting studies, where IOI typically manifests during or shortly after the loading dose phase.” In these cases, patients “developed IOI after a median of 3.5 faricimab injections, ranging from 1 to a maximum of 6 injections before the event.” Inflammation occurred in a median of 28 days after the last injection, but cases developed between 3 and 90 days. “This wide range can be attributed to the occurrence of bilateral asymmetric inflammation in some cases, where 1 eye exhibited more severe symptoms and was therefore evaluated more promptly,” they wrote.
In addition to vigilance and thorough weighing of risks and benefits, the investigators provided further suggestions of practical steps for monitoring patients, including imaging to assess the extent of inflammation and prompt corticosteroid treatment.
A full list of author disclosures can be found in the published research
