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

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