Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: A randomized, controlled trial

Abstract

Objective: To compare the benefits of initiating treatment with methotrexate (MTX) and infliximab (anti–tumor necrosis factor α [anti‐TNFα] monoclonal antibody) with those of MTX treatment alone in patients with rheumatoid arthritis (RA) of ≤3 years' duration. Methods: RA patients were eligible if they had active disease and no prior treatment with MTX or a TNFα inhibitor. One thousand forty‐nine patients were randomly assigned in a 4:5:5 ratio to 3 treatment groups: MTX–placebo, MTX–3 mg/kg infliximab, and MTX–6 mg/kg infliximab. MTX dosages were rapidly escalated to 20 mg/week, and infliximab or placebo infusions were given at weeks 0, 2, and 6, and every 8 weeks thereafter through week 46. Results: At week 54, the median percentage of American College of Rheumatology improvement (ACR‐N) was higher for the MTX–3 mg/kg infliximab and MTX–6 mg/kg infliximab groups than for the MTX–placebo group (38.9% and 46.7% versus 26.4%, respectively; P < 0.001 for both comparisons). Patients in the MTX–3 mg/kg infliximab and MTX–6 mg/kg infliximab groups also showed less radiographic progression than those receiving MTX alone (mean ± SD changes in van der Heijde modification of the total Sharp score at week 54: 0.4 ± 5.8 and 0.5 ± 5.6 versus 3.7 ± 9.6, respectively; P < 0.001 for each comparison). In addition, physical function improved significantly more in the MTX–3 mg/kg infliximab and MTX–6 mg/kg infliximab groups than in the MTX–placebo group. Infliximab therapy was associated with a significantly higher incidence of serious infections, especially pneumonia. Conclusion: For patients with active RA in its early stages, combination therapy with MTX and infliximab provides greater clinical, radiographic, and functional benefits than treatment with MTX alone.