Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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van Roon, E.N. et al.

van Roon, Jansen, van de Laar, Janssen, Yska, Keuper, Houtman, Brouwers,

Therapeutic drug monitoring of A77 1726, the active metabolite of leflunomide: serum concentrations predict response to treatment in patients with rheumatoid arthritis.

BACKGROUND: Leflunomide is the prodrug of the disease modifying antirheumatic metabolite A77 1726. More than 50% of patients withdraw from leflunomide treatment within one year, mainly because of adverse drug reactions. Therapeutic drug monitoring of A77 1726 may be useful in predicting the efficacy of leflunomide treatment. OBJECTIVE: To study the relation between A77 1726 steady state serum concentrations and disease activity using the 28 joint (DAS28) response. METHODS: Outpatients with rheumatoid arthritis on a stable leflunomide dose for >4 months were included. DAS28 score and adverse drug reactions were recorded. Blood samples were taken for determination of A77 1726 concentrations. The primary end point was the relation of serum A77 1726 concentrations with DAS28 response category. RESULTS: Serum A77 1726 concentrations were determined in 52 patients. A receiver operating characteristic (ROC) curve showed an area under the curve (AUC) of 0.73 (95% confidence interval, 0.54 to 0.93) (p<0.05). The sensitivity exceeded 99% at concentrations below 16 mg/l. DAS28 values at the point of sampling showed no relation with A77 1726 concentrations (AUC of the ROC curve = 0.50 (0.33 to 0.67) (NS)). CONCLUSIONS: A77 1726 steady state serum concentrations show a relation with DAS28 response. Determination of serum A77 1726 concentrations in patients with insufficient response to treatment may help when decisions have to be made about continuation of treatment or dose adjustment.[1]

References

Therapeutic drug monitoring of A77 1726, the active metabolite of leflunomide: serum concentrations predict response to treatment in patients with rheumatoid arthritis. van Roon, E.N., Jansen, T.L., van de Laar, M.A., Janssen, M., Yska, J.P., Keuper, R., Houtman, P.M., Brouwers, J.R. Ann. Rheum. Dis. (2005) [Pubmed]

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