A randomized, double-blind, placebo-controlled study to evaluate the addition of methotrexate to etanercept in patients with moderate to severe plaque psoriasis.

BACKGROUND: Etanercept plus methotrexate combination therapy has not been adequately investigated in psoriasis. OBJECTIVES: To evaluate etanercept plus methotrexate vs. etanercept monotherapy in patients with moderate to severe plaque psoriasis who had not failed prior methotrexate or tumour necrosis factor-inhibitor therapy. METHODS: Patients received etanercept 50 mg twice weekly for 12 weeks followed by 50 mg once weekly for 12 weeks and were randomized 1 : 1 to receive methotrexate (7·5-15 mg weekly) or placebo. The primary endpoint was the proportion of patients achieving ≥75% improvement in Psoriasis Area and Severity Index (PASI 75) at week 24. RESULTS: In total, 239 patients were enrolled in each arm. PASI 75 was significantly higher at week 24 for the combination therapy group compared with the monotherapy group (77·3% vs. 60·3%; P < 0·0001). Other PASI improvement scores at week 12 [PASI 75, 70·2% vs. 54·3% (P = 0·01); PASI 50, 92·4% vs. 83·8% (P = 0·01); and PASI 90, 34·0% vs. 23·1% (P = 0·03)] showed similar results as did week 24 PASI 50 (91·6% vs. 84·6%; P = 0·01) and PASI 90 (53·8% vs. 34·2%; P = 0·01). Significantly more patients receiving combination therapy than monotherapy had static Physician's Global Assessment of clear/almost clear at week 12 (65·5% vs. 47·0%; P = 0·01) and week 24 (71·8% vs. 54·3%; P = 0·01). Adverse events (AEs) were reported in 74·9% and 59·8% of combination therapy and monotherapy groups, respectively; three serious AEs were reported in each arm. CONCLUSIONS: Combination therapy with etanercept plus methotrexate had acceptable tolerability and increased efficacy compared with etanercept monotherapy in patients with moderate to severe psoriasis.