Monday, July 15, 2024

Janus Kinase Inhibitors Linked to Decreased Risk of AMD in Autoimmune Disease Patients

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Recent findings indicate that Janus kinase inhibitors (JAKis) may offer a promising therapeutic avenue for patients suffering from autoimmune diseases with a high risk of developing age-related macular degeneration (AMD). The study, drawing on extensive data from both commercial and Medicare databases, provides compelling evidence of the potential benefits of JAKi therapy in reducing AMD incidence, underscoring their expanding role beyond traditional uses.

Study Design and Participants

A comprehensive retrospective observational cohort study was conducted using administrative claims data from the Merative MarketScan research databases and Optum Clinformatics Data Mart databases, covering the period from January 1, 2010, to January 31, 2022. The study focused on patients diagnosed with autoimmune diseases who were treated with JAKis. A total of 9,126 patients from MarketScan and 5,667 from Optum receiving JAKi treatment were matched with patients undergoing non-JAKi-based immunotherapy, employing propensity score matching to ensure comparable groups.

Results and Analysis

The analysis revealed a significant reduction in the incidence of AMD among patients undergoing JAKi therapy. In the MarketScan database, a 49% relative reduction in AMD was observed (10 out of 9,126 JAKi-treated patients compared to 43 out of 9,126 non-JAKi-treated patients). Similarly, the Optum database showed a 73% relative reduction (3 out of 5,667 JAKi-treated patients compared to 21 out of 5,667 non-JAKi-treated patients). The absolute percentage reductions were 0.36% and 0.32%, respectively, favoring the JAKi-treated groups.

These results also highlight the potential for JAKis to improve market access for patients seeking alternatives for AMD prevention, particularly those already managing autoimmune conditions. The inclusion of such therapies could revolutionize treatment protocols and patient outcomes.

The Bayesian Poisson regression models used to estimate the incidence rate ratios further underscore the robustness of these findings, with posterior probabilities of the adjusted risk being less than unity at 97.6% for MarketScan and 98.9% for Optum.

Key Inferences

  • JAKi therapy is associated with a significant reduction in AMD incidence among patients with autoimmune diseases.
  • The study’s findings support the potential expansion of JAKis in therapeutic protocols beyond their conventional uses.
  • Improved market access to JAKi therapies could provide substantial benefits to patients at risk of AMD.
  • Future studies with long-term follow-ups are essential to further validate these results and explore additional disease indications.

The study’s conclusions suggest that JAKi use may be linked to a reduced risk of developing AMD in U.S. adults with significant autoimmune conditions. The absolute percentage reductions observed reinforce the potential role of JAKis in this patient population. Further research is recommended to explore the long-term effects and broader applicability of JAKis in preventing AMD, potentially leading to novel treatment strategies.

Original Article:

JAMA Ophthalmol. 2024 Jul 11. doi: 10.1001/jamaophthalmol.2024.2376. Online ahead of print.

ABSTRACT

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IMPORTANCE: The involvement of chronic inflammation in the pathogenesis of age-related macular degeneration (AMD) opens therapeutic possibilities to AMD management.

OBJECTIVE: To determine whether Janus kinase inhibitors (JAKis) are associated with a reduced risk of AMD development in patients with autoimmune diseases.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective observational cohort study 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. Patients with autoimmune diseases satisfying study eligibility criteria and who received JAKi treatment (9126 in MarketScan and 5667 in Optum) were propensity score matched (1:1) to identical numbers of study-eligible patients who received non-JAKi-based immunotherapy.

EXPOSURE: Treatment duration of 6 months or longer.

MAIN OUTCOMES AND MEASURES: Incidence rates of AMD (exudative and nonexudative) over the first 6 to 18 months of treatment were determined, and bayesian Poisson regression models were used to estimate incidence rate ratios, 95% CIs, and posterior probabilities of AMD.

RESULTS: After matching, female sex represented the majority of the patient population in both MarketScan and Optum (14 019/18 252 [76.6%] and 8563/3364 [75.2%], respectively in the JAKi patient population). More than 60% of the patient population was older than 55 years of age in both cohorts. Over the specified treatment period, a 49% relative reduction in incidence of AMD was observed among patients who received JAKi therapy (10/9126 events; adjusted incidence rate ratio [AIRR], 0.51; 95% CI, 0.19-0.90) vs those who received non-JAKi therapy (43/9126 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. The absolute percentage reductions were 0.36% (MarketScan) and 0.32% (Optum), favoring patients who received JAKi therapy. 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.

CONCLUSIONS AND RELEVANCE: JAKi use may be associated with a reduced risk of incident AMD in US adults with major autoimmune diseases. The absolute percentage reduction is consistent with a potential role for JAKi in this population. Future studies with long-term follow-up are recommended to investigate the association between JAKi use and incident AMD in other disease indications. Investigation into the role of systemic inflammation and JAK-signal transducers and activators of transcription signaling in AMD may improve understanding of the pathophysiology of AMD and lead to new treatment options.

PMID:38990568 | DOI:10.1001/jamaophthalmol.2024.2376

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