Health Economics and Outcomes Research, AbbVie, North Chicago, Illinois.
Genomics Research Center, AbbVie, North Chicago, Illinois.
JAMA Ophthalmol. 2024 Aug 1;142(8):750-758. doi: 10.1001/jamaophthalmol.2024.2376.
The involvement of chronic inflammation in the pathogenesis of age-related macular degeneration (AMD) opens therapeutic possibilities to AMD management.
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.
Treatment duration of 6 months or longer.
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.
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.
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.
慢性炎症在年龄相关性黄斑变性（AMD）发病机制中的参与为 AMD 管理开辟了治疗可能性。
确定 Janus 激酶抑制剂（JAKi）是否与自身免疫性疾病患者 AMD 发病风险降低相关。
设计、设置和参与者：这项回顾性观察性队列研究使用了 Merative MarketScan 研究数据库（商业和医疗保险补充）和 Optum Clinformatics Data Mart 数据库中的行政索赔数据，时间范围为 2010 年 1 月 1 日至 2022 年 1 月 31 日。符合研究入选标准并接受 JAKi 治疗的（MarketScan 中有 9126 例，Optum 中有 5667 例）患者与接受非 JAKi 为基础的免疫治疗的相同数量的符合研究入选标准的患者进行倾向评分匹配（1:1）。
治疗持续时间为 6 个月或更长时间。
在治疗的前 6 至 18 个月内确定 AMD（渗出性和非渗出性）的发生率，并使用贝叶斯泊松回归模型估计 AMD 的发生率比、95%CI 和 AMD 的后验概率。
匹配后，在 MarketScan 和 Optum 中，女性在患者人群中占多数（JAKi 患者人群中分别为 14019/18252[76.6%]和 8563/3364[75.2%]）。在两个队列中，超过 60%的患者年龄大于 55 岁。在规定的治疗期间，接受 JAKi 治疗的患者 AMD 的发生率相对降低了 49%（10/9126 例事件；调整发病率比[AIRR]，0.51；95%CI，0.19-0.90）与接受非 JAKi 治疗的患者（43/9126 例事件；AIRR，1[参考]）相比，在 MarketScan 中，接受 JAKi 治疗的患者 AMD 的发生率相对降低了 73%（3/5667 例事件；AIRR，0.27；95%CI，0.03-0.74）与接受非 JAKi 治疗的患者（21/5667 例事件；AIRR，1[参考]）相比。绝对百分比降低分别为 0.36%（MarketScan）和 0.32%（Optum），有利于接受 JAKi 治疗的患者。在 MarketScan 和 Optum 中，接受 JAKi 治疗的患者发生 AMD 的调整风险小于 1 的后验概率分别为 97.6%和 98.9%。
JAKi 的使用可能与美国患有主要自身免疫性疾病的成年人 AMD 发病风险降低相关。绝对百分比降低与 JAKi 在该人群中的潜在作用一致。建议进行长期随访的未来研究，以调查其他疾病指征中 JAKi 治疗与 AMD 发病之间的关联。对全身炎症和 JAK 信号转导物和转录激活物（JAK-signal transducers and activators of transcription，JAK-STAT）信号在 AMD 中的作用的研究可以提高对 AMD 发病机制的理解，并为新的治疗选择提供依据。
Zotero 插件
