Pharmacokinetics of subcutaneously administered etanercept in subjects with psoriasis

Abstract

Aims: To present the results of the pharmacokinetic analysis of the concentration-time profiles of etanercept, a soluble receptor tumour necrosis factor (TNF) antagonist, in more than 1300 subjects with psoriasis.

Methods: Pharmacokinetic samples were collected in one phase-2 and two phase-3 placebo-controlled, randomized clinical trials. Study 1 evaluated a 25-mg twice weekly (BIW) etanercept dosing regimen administered by subcutaneous (s.c.) injection for 24 weeks. Study 2 evaluated 25-mg BIW and 50-mg BIW s.c. doses for 12 weeks. Study 3 evaluated 25 mg once weekly (QW), 25 mg BIW and 50 mg BIW s.c. doses for 24 weeks.

Results: The mean +/- SD steady-state predose serum concentrations of etanercept for the 25-mg BIW arm at 12 weeks in study 1 were 1590 +/- 885 ng ml(-1). In study 2, mean +/- SD etanercept steady-state concentrations at 12 weeks were 1900 +/- 1110 ng ml(-1) in the 25-mg BIW group and 3830 +/- 1870 ng ml(-1) in the 50-mg BIW group. The mean +/- SD steady-state predose serum concentrations of etanercept at 12 weeks in study 3 were 768 +/- 475 ng ml(-1) for the 25-mg QW regimen, 1990 +/- 1030 ng ml(-1) for the 25-mg BIW regimen and 4020 +/- 2100 ng ml(-1) for the 50-mg BIW regimen.

Conclusions: Pharmacokinetic results were highly consistent across clinical trials. The concentration-time profiles displayed dose proportionality. Etanercept concentrations in subjects with psoriasis are similar to the concentrations in subjects with rheumatoid arthritis.

Figure 1

Mean (± SD) etanercept serum trough concentration–time profiles for the active dosing arms during the blinded period of study 2. 25 mg BIW (□), 50 mg BIW (♦)

Figure 2

Mean (± SD) etanercept serum trough concentration–time profiles for all dosing arms during the blinded period of study 3. ¹Week 24 after receiving active 25 mg BIW for 12 weeks

Figure 3

Mean (± SD) etanercept serum concentration–time profiles at week 1 (a), week 12 (b) and week 24 (c) of the subjects from the PK subset of study 3. ¹Week 24 after receiving active 25 mg BIW for 12 weeks

Figure 4

Mean (± SD) etanercept trough serum concentration–time profiles for the various dosing arms in all studies. (a) study 1 (•), study 2 (▾), study 3 (○); (b) study 2 (▾), study 3 (○)