甲氨蝶呤多聚谷氨酸与甲氨蝶呤在炎症性关节炎、结肠炎和皮炎中的疗效和毒性关系的荟萃分析。

A meta-analysis of methotrexate polyglutamates in relation to efficacy and toxicity of methotrexate in inflammatory arthritis, colitis and dermatitis.

机构信息

Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.

Department of Gastroenterology and Hepatology, Amsterdam UMC, Vrije Universiteit Amsterdam, AGEM Research Institute, Amsterdam, The Netherlands.

出版信息

Br J Clin Pharmacol. 2023 Jan;89(1):61-79. doi: 10.1111/bcp.15579. Epub 2022 Nov 20.

DOI:10.1111/bcp.15579

PMID:36326810

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10099850/

Abstract

AIMS

In immune-mediated inflammatory diseases (IMIDs), early symptom control is a key therapeutic goal. Methotrexate (MTX) is the first-line treatment across IMIDs. However, MTX is underutilized and suboptimally dosed, partly due to the inability of making individualized treatment decisions through therapeutic drug monitoring (TDM). To implement TDM in clinical practice, establishing a relationship between drug concentration and disease activity is paramount. In this meta-analysis, we investigated the relationship between concentrations of MTX polyglutamates (MTX-PG) in erythrocytes and efficacy as well as toxicity across IMIDs.

METHODS

Studies analysing MTX-PG in relation to disease activity and/or toxicity were included for inflammatory arthritis (rheumatoid [RA] and juvenile idiopathic arthritis [JIA]), inflammatory bowel disease (Crohn's and ulcerative colitis) and dermatitis (psoriasis and atopic dermatitis). Meta-analyses were performed resulting in several summary effect measures: regression coefficient (β), correlation coefficient and mean difference (of MTX-PG in responders vs. nonresponders) for IMIDs separately and collectively.

RESULTS

Twenty-five studies were included. In RA and JIA, higher MTX-PG was significantly associated with lower disease activity at 3 months (β: -0.002; 95% confidence interval [CI]: -0.004 to -0.001) and after 4 months of MTX use (β: -0.003; 95% CI: -0.005 to -0.002). Similarly, higher MTX-PG correlated with lower disease activity in psoriasis (R: -0.82; 95% CI: -0.976 to -0.102). Higher MTX-PG was observed in RA, JIA and psoriasis responders (mean difference: 5.2 nmol/L MTX-PG ; P < .01).

CONCLUSION

We showed that higher concentrations of erythrocyte MTX-PG were associated with lower disease activity in RA, JIA and psoriasis. These findings are an important step towards implementation of TDM for MTX treatment across IMIDs.

摘要

目的

在免疫介导的炎症性疾病（IMIDs）中，早期症状控制是一个关键的治疗目标。甲氨蝶呤（MTX）是治疗各种 IMIDs 的一线药物。然而，由于无法通过治疗药物监测（TDM）来做出个体化的治疗决策，MTX 的应用不足且剂量不理想。为了在临床实践中实施 TDM，建立药物浓度与疾病活动之间的关系至关重要。在这项荟萃分析中，我们研究了红细胞中甲氨蝶呤多聚谷氨酸（MTX-PG）浓度与 IMIDs 疗效和毒性之间的关系。

方法

纳入了分析 MTX-PG 与疾病活动和/或毒性之间关系的研究，包括炎症性关节炎（类风湿关节炎[RA]和幼年特发性关节炎[JIA]）、炎症性肠病（克罗恩病和溃疡性结肠炎）和皮肤病（银屑病和特应性皮炎）。进行了荟萃分析，得出了几个综合效应指标：分别和综合分析 IMIDs 时的回归系数（β）、相关系数和 MTX-PG 在应答者与无应答者之间的平均差异。

结果

共纳入 25 项研究。在 RA 和 JIA 中，较高的 MTX-PG 与 3 个月时（β：-0.002；95%置信区间[CI]：-0.004 至 -0.001）和 MTX 治疗 4 个月后（β：-0.003；95% CI：-0.005 至 -0.002）的疾病活动度降低显著相关。同样，较高的 MTX-PG 与银屑病的疾病活动度降低相关（R：-0.82；95% CI：-0.976 至 -0.102）。RA、JIA 和银屑病应答者的 MTX-PG 较高（平均差异：5.2 nmol/L MTX-PG；P <.01）。