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 (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.

Clinical and Radiographic Features of Knee Osteoarthritis of Elderly Patients.

BACKGROUND: Knee osteoarthritis is a common pathology, characterized by a prevalence that increases with age. Absence of anatomo-clinical correlation is a complex management, particularly in a geriatric setting where it is not well studied. OBJECTIVE: The aim of the present study is to investigate the epidemio-clinical profile, functional impairment and radiographic features of knee osteoarthritis in the old patients versus younger patients (<65 years). METHODS: Cross-sectional study includes patients who were monitored for 6 months at a rheumatology department for knee osteoarthritis. Epidemio-clinical, anthropometric and radiographic data were gathered. A comparison was made of these various characteristics between patients of over 65 years of age (group1; n=56) and those under 65 (group2; n=56). RESULTS: The mean age of the group 1 patients was 71±5 with a clear feminine predominance. Comorbidity was observed in two thirds of cases. More than half of them were overweight. Gonalgia had been evolving for approximately 8.4±9.2 years and was bilateral in 82.6% of the cases and of mechanical type in 94.6% of the cases. The patients experienced an average pain scale of 65.2mm. Pain had an anterior site in major of cases. An axial deviation of the lower limbs were observed in 60.7% of the cases and a limited mobility of the knees in 48.2% of the cases. The mean value of Lequesne index was 11.02±4.8. The walking distance was not limited in 37.5% of the cases. Radiographically, knee osteoarthritis was bilateral in all cases and stage 4 was observed in 50% of the cases. Comparative study showed that elderly patients had a smaller waist size (p=0.003), a longer course of gonalgia (p<0.0001), a widespread site of pain (p=0.004), and a more frequent limitation of walking distance (p<0.0001) as well as more axial deviation (p<0.0001) and joint mobility limitation (p=0.005). Gonalgia manifesting during rest was more frequent in elderly patients (p=0.001). In addition, impaired functioning (p=0.001) and the stage of radiographic damage (p=0.02) were more advanced in elderly patients. CONCLUSION: The present study shows that knee osteoarthritis is more severe in the elderly patients in terms of clinical presentation and functional impairment.