Study suggests JAK inhibitors may reduce AMD risk in autoimmune disease patients

(Image Credit: AdobeStock/Lila Patel)

Investigators studying the effects of Janus kinase inhibitor (JAKi) therapy in patients with autoimmune diseases reported that these patients may have a lower risk of developing age-related macular degeneration (AMD).¹ The key factor may be the control of inflammation, according to the first study author Joelle A. Hallak, PhD who is from Health Economics and Outcomes Research, AbbVie, North Chicago, IL.

She and her colleagues explained that the etiology is not completely understood; however, the evidence suggests that inflammation has a role in AMD pathogenesis and progression.^2-4 Chronic low-level local inflammation is present based on the inflammatory mediators present in drusen⁵ and inflammatory cell infiltrates in affected ocular tissues.⁶

In addition to local inflammation, systemic inflammation may also play a role in AMD pathogenesis, they said.^7-10

They also cited studies on the use of oral metformin, which they explained, may reduce chronic low-grade inflammation, and has been associated with a decreased AMD risk in patients with and without diabetes.^10,11

Based on the previously published evidence, the researchers conducted a retrospective observational cohort study in which they used administrative claims data from Merative MarketScan research databases (Commercial and Medicare Supplemental) and Optum Clinformatics Data Mart databases between January 1, 2010, and January 31, 2022. The goal was to establish if JAKis are associated with a reduced risk of AMD development in patients with autoimmune diseases.

Patients were included who had autoimmune diseases and received JAKi treatment (9,126 in MarketScan and 5,667 in Optum) and were propensity score matched (1:1) to patients who had not been treated with Janus kinase immunotherapy. All patients had been treated for a minimum of 6 months.

The main outcome measures were the incidence rates of exudative and nonexudative AMD over the first 6 to 18 months of treatment.

Retrospective study results

About three-quarters of the study patients were women, and 60% were older than 55 years.

The investigators reported, “Over the specified treatment period, a 49% relative reduction in the incidence of AMD was observed among patients who received JAKi therapy (10/9,126 events; adjusted incidence rate ratio [AIRR], 0.51; 95% confidence interval [CI], 0.19-0.90) vs those who received non-JAKi therapy (43/9,126 events; AIRR, 1 [reference]) in MarketScan, and a 73% relative reduction in incidence of AMD was observed among patients who received JAKi therapy (3/5667 events; AIRR, 0.27; 95% CI, 0.03-0.74) vs those who received non-JAKi therapy (21/5667 events; AIRR, 1 [reference]) in Optum.”

They continued, “The absolute percentage reductions were 0.36% (MarketScan) and 0.32% (Optum), favoring patients who received JAKi therapy. The posterior probabilities of the adjusted risk being less than unity were 97.6% (MarketScan) and 98.9% (Optum) for those who received JAKi therapy vs those who received non-JAKi therapy in MarketScan and Optum, respectively.”

The investigators concluded that while the study under discussion provided evidence between JAKi therapy and a reduced risk of developing AMD in patients with autoimmune diseases, they advised that additional larger studies be performed to determine the robustness and duration of this treatment effect.

They also emphasized that the mechanisms of the prophylactic action of JAKi agents against AMD should be determined as well as the differences, between them and non-JAKi immunotherapies.

They concluded, “Our findings suggest that reducing systemic inflammation by inhibiting JAK-STAT signaling represents an additional therapeutic option for AMD management in clinical practice.”

References

1. Hallak JA, Abbasi A, Goldberg RA, et al. Janus kinase inhibitor therapy and risk of age-related macular degeneration in autoimmune disease. JAMA Ophthalmol. Published online July 11, 2024; doi:10.1001/jamaophthalmol.2024.2376

2. Wang Y, Wang VM, Chan CC. The role of anti-inflammatory agents in age-related macular degeneration (AMD) treatment. Eye (Lond). 2011;25:127-139; doi: 10.1038/eye.2010.196

3. Chen M, Xu H. Parainflammation, chronic inflammation, and age-related macular degeneration. J Leukoc Biol. 2015;98:713-725. Doi: 10.1189/jlb.3RI0615-239R

4. Arrigo A, Aragona E, Bandello F. The role of inflammation in age-related macular degeneration: updates and possible therapeutic approaches. Asia Pac J Ophthalmol (Phila). 2023;12:158-167; doi: 10.1097/APO.0000000000000570

5. Anderson DH, Mullins RF, Hageman GS, Johnson LV. A role for local inflammation in the formation of drusen in the aging eye. Am J Ophthalmol. 2002;134:411-431; doi: 10.1016/S0002-9394(02)01624-0

6. Khan AH, Chowers I, Lotery AJ. Beyond the complement cascade: insights into systemic immunosenescence and inflammaging in age-related macular degeneration and current barriers to treatment. Cells. 2023;12:1708; doi: 10.3390/cells12131708

7. Bak M, Sørensen TL, Flachs EM, et al. Age-related macular degeneration in patients with chronic myeloproliferative neoplasms. JAMA Ophthalmol. 2017;135:835-843; doi: 10.1001/jamaophthalmol.2017.2011

8. Liisborg C. Age-related macular degeneration and myeloproliferative neoplasms—a common pathway. Acta Ophthalmol. 2022;100(Suppl 271):3-35; doi: 10.1111/aos.15247PubMedGoogle ScholarCrossref

9. Xiao J, Zhang JY, Luo W, He PC, Skondra D. The emerging role of gut microbiota in age-related macular degeneration. Am J Pathol. 2023;193:1627-1637; doi: 10.1016/j.ajpath.2023.04.006

10. Holtz JK, Thinggaard BS, Grauslund J, Subhi Y. Association between oral metformin use and the risk of age-related macular degeneration: a systematic review with meta-analysis. Acta Ophthalmol. 2023;101:595-605; doi: 10.1111/aos.15655

11. Aggarwal S, Moir J, Hyman MJ, et al. Metformin use and age-related macular degeneration in patients without diabetes. JAMA Ophthalmol. 2024;142:53-57; doi: 10.1001/jamaophthalmol.2023.5478