Study 1 was a Phase 2 study in patients with active, but clinically stable, plaque psoriasis involving ≥ 10% of the body surface area who were ≥ 18 years old. One hundred and twelve (112) patients were randomised to receive a dose of 25 mg of etanercept (n = 57) or placebo (n = 55) twice a week for 24 weeks. Study 2 evaluated 652 patients with chronic plaque psoriasis using the same inclusion criteria as study 1 with the addition of a minimum psoriasis area and severity index (PASI) of 10 at screening. Etanercept was administered at doses of 25 mg once a week, 25 mg twice a week or 50 mg twice a week for 6 consecutive months.
During the first 12 weeks of the double-blind treatment period, patients received placebo or one of the above three etanercept doses. After 12 weeks of treatment, patients in the placebo group began treatment with blinded etanercept (25 mg twice a week); patients in the active treatment groups continued to week 24 on the dose to which they were originally randomised. Study 3 evaluated 583 patients and had the same inclusion criteria as study 2. Patients in this study received a dose of 25 mg or 50 mg etanercept, or placebo twice a week for 12 weeks and then all patients received open-label 25 mg etanercept twice weekly for an additional 24 weeks.
Study 4 evaluated 142 patients and had similar inclusion criteria to studies 2 and 3. Patients in this study received a dose of 50 mg etanercept or placebo once weekly for 12 weeks and then all patients received open-label 50 mg etanercept once weekly for an additional 12 weeks. In study 1, the etanercept-treated group had a significantly higher proportion of patients with a PASI 75 response at week 12 (30%) compared to the placebo-treated group (2%) (p 56% of patients in the etanercept-treated group had achieved the PASI 75 compared to 5% of placebo treated patients. Key results of studies 2, 3 and 4 are shown below.
Responses of patients with psoriasis in studies 2, 3 and 4 *p ≤ 0.0001 compared with placebo a. No statistical comparisons to placebo were made at week 24 in studies 2 and 4 because the original placebo group began receiving etanercept 25 mg BIW or 50 mg once weekly from week 13 to week 24. b. Dermatologist Static Global Assessment. Clear or almost clear defined as 0 or 1 on a 0 to 5 scale. Among patients with plaque psoriasis who received etanercept, significant responses relative to placebo were apparent at the time of the first visit (2 weeks) and were maintained through 24 weeks of therapy.
Study 2 also had a drug withdrawal period during which patients who achieved a PASI improvement of at least 50% at week 24 had treatment stopped. Patients were observed off treatment for the occurrence of rebound (PASI ≥ 150% of baseline) and for the time to relapse (defined as a loss of at least half of the improvement achieved between baseline and week 24). During the withdrawal period, symptoms of psoriasis gradually returned, with a median time to disease relapse of 3 months. No rebound flare of disease and no psoriasis-related serious adverse events were observed. There was some evidence to support a benefit of re-treatment with etanercept in patients initially responding to treatment.
25 Response (%) Study 2 Study 3 Study 4 Placebo n = 166 wk 12 --------Etanercept------- 25 mg 50 mg BIW BIW n = n = n = n = 162 162 164 164 wk wk wk wk 12 24a 12 24a Placebo n = 193 wk 12 -----Etanercept----- 25 mg 50 mg BIW BIW n = 196 n = 196 wk 12 wk 12 Placebo n = 46 wk 12 -----Etanercept----- 50 mg 50 mg QW QW n = 96 n = 90 wk 12 wk 24a PASI 50 14 58* 70 74* 77 9 64* 77* 9 69* 83 PASI 75 4 34* 44 49* 59 3 34* 49* 2 38* 71 DSGAb, clear or almost clear 5 34* 39 49* 55 4 39* 57* 4 39* 64