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

• Published in: British journal of dermatology (1951) Vol. 167; no. 3; pp. 649 - 657
• Main Authors: Gottlieb, A.B., Langley, R.G., Strober, B.E., Papp, K.A., Klekotka, P., Creamer, K., Thompson, E.H.Z., Hooper, M., Kricorian, G.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.09.2012; Wiley-Blackwell
• Subjects: Administration, Cutaneous; Biological and medical sciences; Dermatologic Agents - administration & dosage; Dermatologic Agents - adverse effects; Dermatology; Double-Blind Method; Drug Therapy, Combination - methods; Etanercept; Female; Humans; Immunoglobulin G - administration & dosage; Immunoglobulin G - adverse effects; Male; Medical sciences; Methotrexate - administration & dosage; Methotrexate - adverse effects; Middle Aged; Original; Psoriasis - drug therapy; Psoriasis. Parapsoriasis. Lichen; Receptors, Tumor Necrosis Factor - administration & dosage; Treatment Outcome; Antineoplastic agent; Human; Immunomodulator; Skin disease; Etanercept; Psoriasis; Dermatology; Antipsoriatic agent; Double blind study; Antirheumatic agent; Methotrexate
• ISSN: 0007-0963; 1365-2133
• DOI: 10.1111/j.1365-2133.2012.11015.x

Summary 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.