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

特瑞氟米特 来氟米特 类风湿性关节炎 医学 内科学 药品 药理学 活性代谢物 代谢物 免疫学 多发性硬化 芬戈莫德
作者
R. Tekaya,Ben Tekaya Aicha,Ben Ammar Lobna,S. Issam,BEN SASSI Mouna,O. Saidane,S. Bouden,Ben Brahim Takoua,Ben Abdelghani Kawther,L. Metoui,H. Sahli,I. Mahmoud,L. Abdelmoula
出处
期刊:Drug metabolism and personalized therapy [De Gruyter]
卷期号:38 (1): 79-85 被引量:2
标识
DOI:10.1515/dmpt-2021-0236
摘要

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 (r 2 =0.2264) and the number of swollen joints (r 2 =0.2413). There was a trend towards a positive correlation between Health Assessment Questionnaire (HAQ) and plasma teriflunomide concentration (r 2 =0.1699). Weight was negatively correlated with the residual plasma concentration of teriflunomide (r 2 =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 (r 2 =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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