Inpharma 1510 - 22 Oct 2005

Individualised dosing ofleflunomide in RA?

Greater concentrations of leflunomide’s activemetabolite (A77 1726) indicate greater control ofdisease in patients with rheumatoid arthritis (RA),according to investigators from Australia.

In a cross-sectional study, they compared plasmaconcentrations of A77 1726 with disease activityvariables in 23 patients with RA.

Plasma concentrations of A77 1726 were significantlygreater for patients with < 5 swollen joints, comparedwith patients with > 5 swollen joints (52 mg/L vs30 mg/L). A similar correlation was found whencomparing Short-Form 36 mental summary scores of> 45 with scores < 45 (50 mg/L vs 30 mg/L). Positivetrends towards higher plasma concentrations ofA77 1726 also existed in patients with milder morningstiffness, shorter duration of morning stiffness, superiorphysician global assessments, less tender joints andlower erythrocyte sedimentation rates. There was nosignificant link between plasma concentrations ofA77 1726 and the reporting of adverse reactions.

A population estimate for clearance of A77 1726(0.0184 L/h) was derived by use of a pharmacokineticmodel, but there was considerable interindividualvariability (50.2%) associated with this result. Theinvestigators suggest that their findings could indicate aplace for more flexible dosing of leflunomide.Chan V, et al. Population pharmacokinetics and association between A77 1726plasma concentrations and disease activity measures following administration ofleflunomide to people with rheumatoid arthritis. British Journal of ClinicalPharmacology 60: 257-264, No. 3, Sep 2005 801021140

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Inpharma 22 Oct 2005 No. 15101173-8324/10/1510-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved