Efficacy and safety of infliximab vs. methotrexate in patients with moderate-to-severe plaque psoriasis: results of an open-label, active-controlled, randomized trial (RESTORE1)

Background Infliximab is indicated for treatment of moderate-to-severe plaque psoriasis in adults whose disease cannot be controlled with other systemic therapies, including methotrexate (MTX). To date, no studies have directly compared the efficacy and safety of infliximab and MTX. Objectives To compare the efficacy and safety of infliximab vs. MTX in adults with moderate-to-severe plaque psoriasis. Methods MTX-naive patients (n = 868) were randomized 3 : 1 to receive infliximab 5 mg kg(-1) at weeks 0, 2, 6, 14 and 22 or MTX 15 mg weekly with a dose increase to 20 mg weekly at week 6 if the Psoriasis Area and Severity Index (PASI) response was < 25%. At week 16, patients with < PASI 50 response could switch treatment groups. The primary efficacy endpoint was PASI 75 response at week 16. Major secondary efficacy endpoints were PASI 75 response at week 26, and the proportion of patients achieving a Physician's Global Assessment (PGA) score of cleared (0) or minimal (1) at weeks 16 and 26. Others included Dermatology Life Quality Index, 36-Item Short Form Health Survey, and PGA, PASI 50, PASI 75 and PASI 90 responses over time. Results The primary endpoint was achieved by a significantly greater proportion of infliximab-treated patients (508/653, 78%) than MTX-treated patients (90/215, 42%; P < 0.001). Key secondary endpoints also were achieved by a greater proportion of infliximab-treated patients. Similar responses were observed at week 26 in patients who switched from MTX to infliximab at week 16. Overall adverse event (AE) incidence was comparable between groups, but incidence of serious and severe AEs was slightly higher in the infliximab group. Conclusions Infliximab was well tolerated and more efficacious than MTX in patients with moderate-to-severe plaque psoriasis. Infliximab also was efficacious in patients who failed MTX and switched to infliximab.