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Title: Dose Adjustment Not Necessary in Patients With Rheumatoid Arthritis Treated With TRU-015: Presented at ACCP
URL: http://www.pslgroup.com/dg/22CE96.htm
Doctor's Guide
September 22, 2008

By Crina Frincu-Mallos, PhD

PHILADELPHIA -- September 22, 2008 -- Dose adjustment of TRU-015 by body weight, age, gender, body surface area, or baseline B-cell counts is not necessary in patients with rheumatoid arthritis (RA), since these parameters do not affect the drug's pharmacokinetics in a clinically significant manner, researchers reported here at the American College of Clinical Pharmacology (ACCP) 37th Annual Meeting.

The investigational drug, which is engineered to bind with high specificity to CD20 on pre-B and mature-B lymphocytes, depletes B cells in RA subjects.

The study was conducted to develop a population pharmacokinetics model of TRU-015 in patients with active RA. The secondary objective was to identify significant covariates that would affect the pharmacokinetics of the drug and the dosing strategy, said investigator Cathye Shu, Translational Development, PhD, Wyeth Research, Collegeville, Pennsylvania, in a poster presentation on September 14.

A total of 62 men and 211 women, a median of 53 years old (range, 20-73 years), were accrued in 2 TRU-015 studies and were pooled for the purpose of this analysis. Their serum TRU-015 concentration data were evaluated using population analysis by the first-order conditional estimates algorithm interaction method in a nonlinear mixed effects modelling approach.

Demographic data and disease-related covariate factors were evaluated with regard to their impact on TRU-015 pharmacokinetics.

The TRU-015 clearance (CL) was 17.4 mL/hr, whereas the volume of distribution (Vz) was estimated at 3.3 L. Both CL and Vz were affected by the patient's body weight.

However, incorporation of body weight as a covariate resulted in a statistically insignificant reduction in interindividual variability in both CL and Vz (<10%). Furthermore, the models indicated that TRU-015 exposures at a fixed dose resulted in only slight differences among RA patients with very different body weight.

Based on these data, the investigators concluded that a 2-compartment structure model describes the PK of TRU-015 in an adequate fashion, with moderate interindividual variability on CL and Vz.

Funding for this study was provided by Trubion Pharmaceuticals.


[Presentation title: Population Pharmacokinetic Analysis of TRU-015 in Patients With Active Rheumatoid Arthritis. Abstract 126]

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