A Pilot Dose-Finding Study of Etanercept in Rheumatoid Arthritis.

A randomized, parallel-dose study assessed the pharmacokinetics (PK) and pharmacodynamics (PD) of etanercept in 61patients with rheumatoid arthritis (RA) who received doses from 10 mg once-weekly to 50mg twice-weekly for 4 weeks. Empiric application of a maximal-effect (E-max) model to pooled steady-state concentrations (C-ss) and PD markers provided half-maximal-effect concentration estimates of 567, 573, 465, 87, and 159 ng/mL for change from baseline in number of swollen joints, number of painful joints, erythrocyte sedimentation rate, interleukin-6, and matrix metalloproteinase-3, respectively. C-ss >approximate to 2,000 ng/mL did not appear to offer additional benefit. It was concluded that the middle doses, 10mg twice-weekly, 50mg every 2 weeks, and 50mg once-weekly, would provide C-ss in the target range of 500-2,000ng/mL. The revised US Food and Drug Administration guideline for development of medicines for treatment of RA encourages a study design incorporating PK/PD assessment to inform later studies.