Paediatric plaque psoriasis outcomes at 12 weeks Etanercept 0.8 mg/kg Once Weekly Placebo (N = 105) (N = 106) PASI 75, n (%) 60 (57%) a 12 (11%) PASI 50, n (%) 79 (75%) a 24 (23%) sPGA “clear” or “minimal”, n (%) 56 (53%) a 14 (13%) Abbreviation: sPGA-static Physician Global Assessment a. p After the 12-week double-blind treatment period, all patients received etanercept 0.8 mg/kg (up to 50 mg) once weekly for additional 24 weeks. Responses observed during the open-label period were similar to those observed in the double-blind period.
During a randomised withdrawal period, significantly more patients re-randomised to placebo experienced disease relapse (loss of PASI 75 response) compared with patients re-randomised to etanercept. With continued therapy, responses were maintained up to 48 weeks. The long-term safety and effectiveness of etanercept 0.8 mg/kg (up to 50 mg) once weekly was assessed in an open-label extension study of 181 paediatric subjects with plaque psoriasis for up to 2 years beyond the 48 week study discussed above. Long-term experience with etanercept was generally comparable to the original 48-week study and did not reveal any new safety findings.
5.2 Pharmacokinetic properties Etanercept serum values were determined by an Enzyme-Linked Immunosorbent Assay (ELISA) method, which may detect ELISA-reactive degradation products, as well as the parent compound. Absorption Etanercept is slowly absorbed from the site of subcutaneous injection, reaching maximum concentration approximately 48 hours after a single dose. The absolute bioavailability is 76%. With twice-weekly doses, it is anticipated that steady-state concentrations are approximately twice as high as those observed after single doses.
After a single subcutaneous dose of 25 mg etanercept, the average maximum serum concentration observed in healthy volunteers was 1.65 ± 0.66 µg/ml, and the area under the curve was 235 ± 96.6 µg hr/ml. Mean serum concentration profiles at steady state in treated RA patients were C max of 2.4 mg/l vs. 2.6 mg/l, C min of 1.2 mg/l vs. 1.4 mg/l, and partial AUC of 297 mg hr/l vs. 316 mg hr/l for 50 mg etanercept once weekly (n = 21) vs. 25 mg etanercept twice weekly (n = 16), respectively.
In an open-label, single-dose, two-treatment, crossover study in healthy volunteers, etanercept administered as a single 50 mg/ml injection was found to be bioequivalent to two simultaneous injections of 25 mg/ml. In a population pharmacokinetics analysis in ankylosing spondylitis patients, the etanercept steady state AUCs were 466 µg hr/ml and 474 µg hr/ml for 50 mg etanercept once weekly (N = 154) and 25 mg twice weekly (N = 148), respectively. Distribution A biexponential curve is required to describe the concentration time curve of etanercept. The central volume of distribution of etanercept is 7.6 l, while the volume of distribution at steady-state is 10.4 l. Elimination 28