Drug metabolism and personalized therapy · 2022
Therapeutic drug monitoring of teriflunomide: do plasma concentrations predict response to leflunomide in patients with rheumatoid arthritis?
СтатьяНазвание и аннотация: Перевод в очереди
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Rawdha Tekaya, Aicha Ben Tekaya, Lobna Ben Ammar, Issam Salouaje, Mouna Ben Sassi, Olfa Saidane, Selma Bouden, Takoua Ben Brahim, Kawther Ben Abdelghani, Leila Metoui, Hana Sahli, Ines Mahmoud, Leila Abdelmoula
Аннотация
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.
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.