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.
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.
Authors: S G Eckhardt; J Rizzo; K R Sweeney; G Cropp; S D Baker; M A Kraynak; J G Kuhn; M A Villalona-Calero; L Hammond; G Weiss; A Thurman; L Smith; R Drengler; J R Eckardt; J Moczygemba; A L Hannah; D D Von Hoff; E K Rowinsky Journal: J Clin Oncol Date: 1999-04 Impact factor: 44.544
Authors: E N van Roon; J P Yska; J Raemaekers; T L Th A Jansen; M van Wanrooy; J R B J Brouwers Journal: J Pharm Biomed Anal Date: 2004-09-21 Impact factor: 3.935
Authors: V Mladenovic; Z Domljan; B Rozman; I Jajic; D Mihajlovic; J Dordevic; M Popovic; M Dimitrijevic; M Zivkovic; G Campion Journal: Arthritis Rheum Date: 1995-11
Authors: J M van Woerkom; A A Kruize; R Geenen; E N van Roon; R Goldschmeding; S M M Verstappen; J A G van Roon; J W J Bijlsma Journal: Ann Rheum Dis Date: 2007-01-12 Impact factor: 19.103
Authors: Ashley M Hopkins; Michael D Wiese; Susanna M Proudman; Catherine E O'Doherty; Richard N Upton; David J R Foster Journal: Br J Clin Pharmacol Date: 2015-10-28 Impact factor: 4.335
Authors: Michael D Wiese; Matthew Schnabl; Catherine O'Doherty; Llewellyn D Spargo; Michael J Sorich; Leslie G Cleland; Susanna M Proudman Journal: Arthritis Res Ther Date: 2012-07-12 Impact factor: 5.156