Real-World Evidence Links Faricimab to Rare Eye Adverse Effects

A retrospective case series suggested that faricimab (Vabysmo) intravitreal injections may be associated with rare cases of noninfectious intraocular inflammation.

Over a 22-month period, 12 eyes from seven patients with neovascular age-related macular degeneration or diabetic macular edema presented with noninfectious intraocular inflammation after faricimab injections, including two eyes that developed retinal vasculitis, reported researchers led by Sandrine Zweifel, MD, PhD, of University Hospital Zurich in Switzerland, and colleagues.

One of the two eyes had an occlusive form of vasculitis of the arteries and veins, resulting in subsequent macular capillary nonperfusion and clinically relevant irreversible vision deterioration, they noted in JAMA Ophthalmology.

Vision didn’t substantially change for the remaining eyes, which were characterized by moderate anterior segment inflammation.

“Although the findings of our study do not establish causality, eye doctors should be aware of the rare but serious risk of retinal vasculitis, including occlusive forms that can lead to irreversible vision loss,” Zweifel told MedPage Today.

Faricimab, a humanized, bispecific, immunoglobulin G monoclonal antibody, received FDA approval as an intravitreal injection for the treatment of neovascular age-related macular degeneration and diabetic macular edema in 2022, and macular edema secondary to retinal vein occlusion in 2023.

“It works by targeting and inhibiting two pathways” — vascular endothelial growth factor A (VEGF-A) and angiopoietin 2 — “that contribute to blood vessel leakage and inflammation in the retina, helping to reduce vision loss and improve outcomes for patients with these conditions,” Zweifel said.

The authors sought to add real-world findings to existing knowledge about the therapy’s side effects. Earlier, “trials demonstrated that the drug is generally well-tolerated, with side effects comparable to other treatments in its class, such as anti-VEGF therapies,” Zweifel noted.

Previous phase III trials linked the drug to intraocular inflammation rates ranging from 0.6% to 2.2%, and manufacturer Genentech warned last year of post-marketing reports of retinal vasculitis with or without occlusion. “As of the end of August 2023, with 1.5 million vials dosed globally, the estimated reporting rate of retinal vasculitis with occlusion is 0.06/10,000 injections (for retinal vasculitis with or without occlusion: 0.17/10,000 injections),” the company said.

Zweifel said it’s not clear why faricimab might cause intraocular inflammation or retinal vasculitis. “Further studies are necessary to address this question comprehensively.”

Sally S. Ong, MD, of Wake Forest University School of Medicine in Winston-Salem, North Carolina, who wasn’t involved in the study, told MedPage Today that other reports of intraocular inflammation following faricimab injections have been recently published, with one study showing “that the risk of intraocular inflammation including vasculitis was low and similar among faricimab, aflibercept [Eylea], and ranibizumab [Lucentis],” she said.

In this study, “bilateral involvement occurred in five out of seven patients and in both patients who developed vasculitis,” she noted. “This seems to suggest that some patients might be more at risk for developing intraocular inflammation. These patients may have underlying autoimmune conditions that may not be diagnosed or are anti-drug antibody positive. Perhaps this may be a reason to consider avoiding same-day bilateral injections in patients who may be at risk for these events, although at this time we don’t really know which patients are at risk.”

Ong pointed out that faricimab is “a highly efficacious treatment option for many patients. These safety events are rare, so I don’t think this report is going to necessarily hinder retina specialists from continuing to use it.”

However, “it is important to be cognizant of these possible safety risks. Patients should be adequately counseled about the benefits versus risks of these injections, so they will return in a timely manner if they develop any concerning symptoms,” she added.

This case series was conducted in an academic-based tertiary referral center in Switzerland among patients referred for intraocular inflammation soon after receiving faricimab 6 mg (0.05 mL of a 120-mg/mL solution) between June 2022 and March 2024. Mean age was 73.3, and 57.1% were women.

The intraocular inflammation event occurred after a median of 3.5 faricimab injections. The median interval between the last faricimab injection and the diagnosis of inflammation was 28 days. Increased intraocular pressure of 30 mm Hg or higher was found in three eyes.

Symptoms of intraocular inflammation onset included floaters, ocular discomfort, pain, and decreased visual acuity. Six eyes were completely asymptomatic and found to have intraocular inflammation on routine follow-up examination.

Study limitations included its retrospective nature and the inability to determine causation. It was also possible that some patients may have been treated for intraocular inflammation without being referred to the tertiary care center.