Therapeutic drug monitoring of teriflunomide: do plasma concentrations predict response to leflunomide in patients with rheumatoid arthritis?

Q2 Pharmacology, Toxicology and Pharmaceutics Drug metabolism and personalized therapy Pub Date : 2023-03-01 DOI:10.1515/dmpt-2021-0236
Tekaya Rawdha, Ben Tekaya Aicha, Ben Ammar Lobna, Salouaje Issam, Ben Sassi Mouna, Saidane Olfa, Bouden Selma, Ben Brahim Takoua, Ben Abdelghani Kawther, Metoui Leila, Sahli Hana, Mahmoud Ines, Abdelmoula Leila
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引用次数: 3

Abstract

Objectives: Leflunomide is a commonly used treatment for rheumatoid arthritis. It acts by inhibiting dihydroorotate dehydrogenase through its active metabolite teriflunomide. The objective of the study was to investigate the relation between plasma-concentration of teriflunomide and disease-activity in rheumatoid arthritis.

Methods: Data were collected from patients with rheumatoid arthritis on a stable leflunomide dose for at least 2 months. Socio-demographic data, disease characteristics and DAS28 score were recorded. Blood samples were taken for determination of teriflunomide concentration.

Results: A total of 32 serum concentration-time measurements were collected. The concentration of teriflunomide was positively correlated with disease duration of RA (r2=0.2264) and the number of swollen joints (r2=0.2413). There was a trend towards a positive correlation between Health Assessment Questionnaire (HAQ) and plasma teriflunomide concentration (r2=0.1699). Weight was negatively correlated with the residual plasma concentration of teriflunomide (r2=0.2483). However, there was no significant correlation between residual-plasma-concentration of teriflunomide and the following parameters: age, sex, number of tender painful joints, patient-global-assessment, C-reactive protein (CRP) and duration of prescription of leflunomide. We did not find association between disease-activity and residual-plasma-concentration of teriflunomide (r2=0.0021) and haven't been able to define the threshold value of residual-plasma-concentration of leflunomide predictive of a good-response.

Conclusions: We did not find a concentration-effect-relationship. However, therapeutic drug monitoring of teriflunomide may be useful to ensure adherence and evaluate toxic-levels in case of adverse-events.

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替氟米特的治疗药物监测:血浆浓度是否能预测类风湿关节炎患者对来氟米特的反应?
目的:来氟米特是一种常用的治疗类风湿性关节炎的药物。它通过其活性代谢物特立氟米特抑制二氢乙酸脱氢酶起作用。本研究的目的是探讨类风湿关节炎患者特立氟米特血药浓度与疾病活动度的关系。方法:收集使用稳定来氟米特剂量至少2个月的类风湿关节炎患者的数据。记录社会人口学资料、疾病特征和DAS28评分。取血测定特立氟米特浓度。结果:共采集32项血清浓度-时间测定。特立氟米特浓度与RA病程(r2=0.2264)、肿胀关节数(r2=0.2413)呈正相关。健康评估问卷(HAQ)与特立氟米特血药浓度呈正相关(r2=0.1699)。体重与特立氟米特血浆残留浓度呈负相关(r2=0.2483)。然而,特氟米特血浆残留浓度与以下参数:年龄、性别、压痛关节数量、患者总体评估、c反应蛋白(CRP)和来氟米特处方时间无显著相关性。我们没有发现疾病活动性与特氟米特血浆残留浓度之间的关联(r2=0.0021),也无法确定来氟米特血浆残留浓度预测良好反应的阈值。结论:我们没有发现浓度-效应关系。然而,对特立氟米特的治疗药物监测可能有助于确保依从性,并在发生不良事件时评估毒性水平。
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来源期刊
Drug metabolism and personalized therapy
Drug metabolism and personalized therapy Pharmacology, Toxicology and Pharmaceutics-Pharmacology, Toxicology and Pharmaceutics (all)
CiteScore
2.30
自引率
0.00%
发文量
35
期刊介绍: Drug Metabolism and Personalized Therapy (DMPT) is a peer-reviewed journal, and is abstracted/indexed in relevant major Abstracting Services. It provides up-to-date research articles, reviews and opinion papers in the wide field of drug metabolism research, covering established, new and potential drugs, environmentally toxic chemicals, the mechanisms by which drugs may interact with each other and with biological systems, and the pharmacological and toxicological consequences of these interactions and drug metabolism and excretion. Topics: drug metabolizing enzymes, pharmacogenetics and pharmacogenomics, biochemical pharmacology, molecular pathology, clinical pharmacology, pharmacokinetics and drug-drug interactions, immunopharmacology, neuropsychopharmacology.
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