Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial

Background Not all patients with rheumatoid arthritis can tolerate or respo nd to methotrexate, a standard treatment for this disease. There is evidenc e that antitumour necrosis factor alpha (TNF alpha) is efficacious in relie f of signs and symptoms. We therefore investigated whether infliximab, a ch imeric human-mouse anti-TNF alpha monoclonal antibody would provide additio nal clinical benefit to patients who had active rheumatoid arthritis despit e receiving methotrexate. Methods In an international double-blind placebo-controlled phase III clini cal trial, 428 patients who had active rheumatoid arthritis, who had receiv ed continuous methotrexate for at least 3 months and at a stable dose for a t least 4 weeks, were randomised to placebo (n=88) or one of four regimens of infliximab at weeks 0, 2, and 6. Additional infusions of the same dose w ere given every 4 or 8 weeks thereafter on a background of a stable dose of methotrexate (median 15 mg/week for greater than or equal to 6 months; ran ge 10-35 mg/wk). Patients were assessed every 4 weeks for 30 weeks. Findings At 30 weeks, the American College of Rheumatology (20) response cr iteria, representing a 20% improvement from baseline, were achieved in 53, 50, 58, and 52% of patients receiving 3 mg/kg every 4 or 8 weeks or 10 mg/k g every 4 or 8 weeks, respectively, compared with 20% of patients receiving placebo plus methotrexate (p<0.001 for each of the four infliximab regimen s vs placebo). A 50% improvement was achieved in 29, 27, 26, and 31% of inf liximab plus methotrexate in the same treatment groups, compared with 5% of patients on placebo plus methotrexate (p<0.001). Infliximab was well-toler ated; withdrawals for adverse events as well as the occurrence of serious a dverse events or serious infections did not exceed those in the placebo gro up. Interpretation During 30 weeks, treatment with infliximab plus methotrexate was more efficacious than methotrexate alone in patients with active rheum atoid arthritis not previously responding to methotrexate.