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 61 patients with rheumatoid arthritis (RA) who received doses from 10 mg once‐weekly to 50 mg 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) >∼2,000 ng/mL did not appear to offer additional benefit. It was concluded that the middle doses, 10 mg twice‐weekly, 50 mg every 2 weeks, and 50 mg once‐weekly, would provide C(ss) in the target range of 500–2,000 ng/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.