JAK inhibitors for autoimmune disease may confer protection against AMD

The use of Janus kinase (JAK) inhibitors in the treatment of major autoimmune diseases appears to reduce the risk of age-related macular degeneration (AMD) for people over 40 years of age, according to a study.

Analyses of claims data from the MarketScan and Optum Clinformatics databases showed that JAK inhibitors were associated with a substantially lower incidence of AMD compared with other immunotherapies over the first 6 to 18 months of treatment.

The relative reduction in AMD incidence with JAK inhibitors was 73 percent higher in the Optum cohort (adjusted incidence rate ratio [aIRR], 0.27, 95 percent confidence interval [CI], 0.03–0.74) and 49 percent higher in the MarketScan cohort (aIRR, 0.51, 95 percent CI, 0.19–0.90). The corresponding absolute percentage reductions were 0.32 percent and 0.36 percent. [JAMA Ophthalmol 2024;doi:10.1001/jamaophthalmol.2024.2376]

The posterior probability of avoiding AMD in patients who received JAK inhibitor therapy was 97.59 percent in MarketScan and 98.94 percent in Optum.

Similar results were obtained in a sensitivity analysis limited to participants who were at least 50 years of age, which the investigators noted to be the commonly accepted minimum age threshold for AMD development.

“Our findings suggest that reducing systemic inflammation by inhibiting JAK signal transducers and activators of transcription (STAT) signalling represents an additional therapeutic option for AMD management in clinical practice,” the investigators said.

“Involvement of local inflammation in AMD pathogenesis is widely accepted, [but] emerging evidence suggests that systemic inflammation may also contribute to this process… However, due to systemic drug administration, the present study is unable to differentiate between the potential systemic vs local (retinal) anti-inflammatory effects of JAK inhibitor therapy in reducing the risk of AMD,” they added.

The investigators called for more studies to shed light into the complex immunological and inflammatory processes at play in the pathophysiology of AMD.

The MarketScan dataset included 9,126 patients who received JAK inhibitor therapy and 9,126 propensity-score matched patients who did not receive such therapy, whereas the Optum dataset consisted of 5,667 propensity-score matched patients in each group. The proportion of patients aged ≥65 years was higher in Optum than Marketscan (34.1 percent vs 16.7 percent), as was the mean Charlson comorbidity index (1.9–2.0 vs 1.5–1.6).

Compared with MarketScan, Optum had a higher prevalence of atopic dermatitis (6.3 percent vs 3.2 percent) and psoriasis (12.8 percent vs 8.5 percent). Ocular comorbidities were well balanced between individuals who received and did not receive JAK inhibitors. The most common comorbidities were cataract (MarketScan: 7.6 percent vs 8.8 percent; Optum: 10.7 percent vs 11.5 percent, respectively) and ocular surface disease (MarketScan: 9.0 percent vs 11.5 percent; Optum: 11.7 percent vs 13.6 percent, respectively).

“The reason for the difference in the extent of [AMD] risk reduction between the MarketScan and Optum study populations is unclear… [but] may potentially be related to [the Optum database population] being an older age group with greater comorbidity,” the investigators said.