RESEARCH - Monitoring of A77 1726, the active metabolite of Arava: serum concentrations predict response to treatment in patients with RA

[Guest guest]

Ann Rheum Dis. 2004 Sep 2 [Epub ahead of print]

Therapeutic drug monitoring of A77 1726, the active metabolite of

leflunomide: serum concentrations predict response to treatment in

patients with rheumatoid arthritis.

Van Roon EN, Jansen TL, Van De Laar MA, Janssen M, Yska JP, Keuper R,

Houtman PM, Brouwers JR.

Medisch Centrum Leeuwarden, The Netherlands.

OBJECTIVES: Leflunomide is the prodrug of the disease-modifying

antirheumatic metabolite A77 1726. Over 50% of patients withdraw from

leflunomide therapy within 1 year after start of treatment, mainly

because of adverse drug reactions. Therapeutic drug monitoring of A77

1726 may be useful to predict efficacy of leflunomide treatment. We have

studied the relationship between A77 1726 steady state serum

concentrations and disease activity using 28 joints (DAS28),

respectively DAS28 response. METHODS: Outpatients with rheumatoid

arthritis on a stable leflunomide dose > 4 months were included. DAS28

parameters and adverse drug reactions were registered. Blood samples

were drawn for determination of the A77 1726 concentration. RESULTS: In

fifty-two patients A77 1726 serum concentrations were determined.

Concerning the primary end point, the relation of A77 1726 serum

concentrations with DAS28-response category, the Receiver Operating

Characteristics (ROC) curve shows an area under the curve (AUC) of 0.73

(95% confidence interval (CI95) 0.54- 0.93; p<0.05), sensitivity

exceeding 99% at concentrations below 16 mg/L. Concerning the secondary

end point, DAS28 values at the moment of sampling show no relationship

between A77 1726 concentrations, with AUC of the ROC-curve 0.50 (CI95

0.33-0.67; NS).

CONCLUSIONS: A77 1726 steady state serum concentrations show a

relationship with DAS28 response. Determination of A77 1726 serum

concentrations for patients with insufficient response to therapy may

offer clinically relevant information for decisions on treatment

continuation or dose adjustment.

PMID: 15345501

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

5345501 & dopt=Abstract

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org