The use of Janus kinase inhibitors compared to other immunotherapies in individuals over 40 years old with autoimmune diseases was linked to a significantly lower risk of developing age-related macular degeneration during the first 6 to 18 months of treatment, according to new research.

“Although the retina is an immune-privileged tissue protected by the blood-retina barrier and the local immune regulatory system, the blood-retina barrier does not completely prevent entry of circulating cells,” researchers explained in a study, published in JAMA Ophthalmology. Features of systemic inflammatory involvement in the development of AMD include hyperactivation of JAK and other signaling pathways and elevation of c-reactive protein and inflammatory cytokines.

The study aimed to track the development of AMD in patients after they began immunotherapy, indicated by a diagnosis of nonexudative, drusen (degenerative), or exudative AMD. Patients were monitored from the start of their treatment until they were diagnosed with AMD, their insurance plan ended, or until January 31, 2022, whichever came first.

A significant reduction in AMD incidence was found among patients treated with JAKi. In a MarketScan cohort, JAKi therapy was associated with a 49% reduction in AMD incidence (AIRR, 0.51; 95% CI, 0.19-0.90). In an Optum cohort, the reduction was 73% (AIRR, 0.27; 95% CI, 0.03-0.74). The absolute percentage reductions were 0.36% (MarketScan) and 0.32% (Optum), which are also “consistent with a potential role for JAKi in this population of patients with autoimmune disease.”

Investigators outlined evidence that connects inflammation and AMD:

• The presence of inflammatory mediators in drusen and inflammatory cell infiltrates in ocular tissue indicate chronic, low-level inflammation
• Polymorphism in immune-related genes is associated with AMD risk
• A previous study reported “upregulation of genes associated with complement system activation in advanced AMD”
• Both chronic inflammation and advanced AMD with geographic atrophy demonstrate overactivation of the complement system
• Myeloproliferative neoplasms are associated with chronic systemic inflammation and increased risk of AMD
• Gut microbiota that may promote inflammation could also be associated with AMD
• Oral metformin reduces both chronic low-level inflammation and AMD risk

A full list of author disclosures can be found in the published research.