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ABCC2 转运蛋白基因多态性预测银屑病患者甲氨蝶呤药物的生存情况。

Polymorphism in Gene for ABCC2 Transporter Predicts Methotrexate Drug Survival in Patients with Psoriasis.

机构信息

Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000 Ljubljana, Slovenia.

Krka, d. d., Novo Mesto, Šmarješka cesta 6, 8000 Novo Mesto, Slovenia.

出版信息

Medicina (Kaunas). 2021 Oct 1;57(10):1050. doi: 10.3390/medicina57101050.

Abstract

: Methotrexate is widely prescribed for the treatment of moderate-to-severe psoriasis. As drug survival encompasses efficacy, safety, and treatment satisfaction, such studies provide insights into successful drug treatments in the real-life scenario. The objective was to define methotrexate drug survival and reasons for discontinuation, along with factors associated with drug survival, in a cohort of adult patients with moderate-to-severe plaque psoriasis. : Data on methotrexate treatment were extracted from our institutional registry. Drug survival was estimated by Kaplan-Meier analysis, and predictors of drug survival were analyzed by Cox proportional hazards regression. : We included 133 patients treated with methotrexate. Due to significant effects of the year of treatment initiation, drug survival analysis was performed for 117 patients who started methotrexate in 2010 or later. Median methotrexate drug survival was 11.0 months. Overall, 89% of patients discontinued treatment, with over half of these (51%) due to lack of efficacy. Significantly longer drug survival was seen for patients who discontinued treatment due to lack of efficacy versus drug safety ( = 0.049); when stratified by sex, this remained significant only for women ( = 0.002). The patient rs717620 genotype was significantly associated with drug survival in both univariate log-rank and multivariate Cox regression analyses, with variant T allele associated with longer drug survival (hazard ratio, 0.606; 95% confidence interval, 0.380-0.967; = 0.036). : We have identified the novel association of patient rs717620 genotype with methotrexate drug survival. This pharmacogenetic marker might thus help in the management of psoriasis patients in daily practice.

摘要

甲氨蝶呤广泛用于治疗中重度银屑病。由于药物存活率涵盖了疗效、安全性和治疗满意度,因此此类研究为现实生活中成功的药物治疗提供了深入了解。本研究旨在确定中重度斑块型银屑病成年患者中甲氨蝶呤的药物存活率和停药原因,以及与药物存活率相关的因素。

我们从机构登记处提取了甲氨蝶呤治疗的数据。通过 Kaplan-Meier 分析估计药物存活率,并通过 Cox 比例风险回归分析药物存活率的预测因素。

我们纳入了 133 名接受甲氨蝶呤治疗的患者。由于治疗起始年份的显著影响,我们对 2010 年或之后开始使用甲氨蝶呤的 117 名患者进行了药物存活率分析。甲氨蝶呤药物存活率的中位数为 11.0 个月。总体而言,89%的患者停止了治疗,其中一半以上(51%)是因为疗效不佳。由于疗效不佳而停止治疗的患者与因药物安全性而停止治疗的患者相比,药物存活率显著延长(=0.049);按性别分层后,这一结果仅在女性中具有统计学意义(=0.002)。在单因素对数秩和多因素 Cox 回归分析中,患者 rs717620 基因型与甲氨蝶呤药物存活率显著相关,变异 T 等位基因与更长的药物存活率相关(风险比,0.606;95%置信区间,0.380-0.967;=0.036)。

我们发现了患者 rs717620 基因型与甲氨蝶呤药物存活率的新关联。因此,这种药物遗传学标志物可能有助于指导日常实践中银屑病患者的管理。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de09/8539794/f0d7718bf22d/medicina-57-01050-g001.jpg

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