JAK Inhibitors Linked to Lower AMD Risk in Autoimmune Patients, suggests JAMA study

Age-related Macular Degeneration presents one of the surfacing enormous reasons for blindness and generally occurs in older individuals. At this point, there is no treatment for the condition with regard to the AMD dry form. JAK inhibitors were licensed by the FDA in 2011, but have been primarily used in treating cancer and autoimmune disorders. There is some new evidence from recent studies showing that inflammation and immunological pathways could be associated with the development of AMD.

A study led by Dr. Nizar Smaoui of AbbVie assessed the insurance-claimed data for probes with respect to the incidence of AMD in patients with autoimmune disorders exposed to JAK inhibitors. This research used two large administrative databases, MarketScan and Optum, from 2010-2022.

Overall, two cohorts comprising more than 29,000 subjects were included from two databases. Each JAK inhibitor patient was matched on age, sex, race/ethnicity, geography, and autoimmune diagnosis, among other factors, to a patient treated with another type of immune-modulating drug. The demographic characteristics of the cohorts were matched for the MarketScan cohort with 18,252 patients,   % women, and for the Optum cohort, %. Moreover, more than % of the study subjects in both cohorts were 55 or older in age. The largest number among them was for rheumatoid arthritis treatment, with the others including psoriasis, psoriatic arthritis, and ulcerative colitis.

The key findings from the study are as follows:

• It was shown that the patients who used JAK inhibitors had a significantly lower rate of AMD compared to the ones using other drugs.

• With an aIRR of 0.51 and a 95% CI of 0.19 to 0.90, this represents a roughly 50% reduction in the MarketScan cohort.

• This was reflected in an adjusted incidence rate ratio of 0.27, with a 95% confidence interval of 0.03-0.74—nearly a 75 percent reduction—in the Optum cohort.

• The absolute risk reductions were 0.36% in the MarketScan cohort and 0.32% in the Optum cohort.

• AMD was a rare event in both cohorts. Among more than 18,000 patients in the MarketScan group, 53 new cases developed (10 in JAK inhibitor users and 43 in non-users).

• In the Optum group, 24 cases were diagnosed (three in users and 21 in non-users).

These findings permit the inference that a strong association might exist between JAK inhibitors and a reduced AMD incidence. remains there, the study could support the hypothesis that inflammation and immune pathways play a role in the pathogenesis or progression of AMD, he said. However, he then added that further clinical studies are required to confirm these results.

Dr. Sumit Sharma of the Cleveland Clinic, who was not involved in the study, found the results promising but said that the small population size and retrospective nature of the study necessarily limit the implications of such studies. He required well-designed clinical trials to explore the potential for JAK inhibitors to treat AMD, especially given both the high risk of side effects and FDA warnings about cardiovascular risks associated with these drugs.

The limitations of this study are that it was retrospective, nonrandomized, and observational. It did not educate regarding the severity of autoimmune diseases, distinguish between "wet" and "dry" forms of AMD, different JAK inhibitor products, or their indications. In addition, the data could not confirm that all patients received equivalent eye exams or that such exams were correctly coded.

Given that JAK inhibitors are associated with a risk of AMD among patients with autoimmune disorders, they could not be recommended for the treatment of AMD based on this research. Instead, solid clinical trials with less risk of side effects should be conducted in this respect.

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