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 ␣ [anti-TNF␣] monoclonalantibody) 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 TNF␣ 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.

Infliximab treatment maintains employability in patients with early rheumatoid arthritis

“…Details of the design of ASPIRE have been reported previously (19). Briefly, patients who were methotrexate (MTX) naive, had active RA, and had a history of persistent synovitis (for at least 3 months but no longer than 3 years from the date of diagnosis) began receiving MTX therapy with rapid dose escalation to 20 mg/week and were randomly assigned in a 5:5:4 ratio to receive either infliximab 3 mg/kg, infliximab 6 mg/kg, or placebo infusions at weeks 0, 2, and 6 and then every 8 weeks through week 46.…”

“…signs and symptoms of disease, slow the rate of radiographic progression, and improve functional capacity (13)(14)(15)(16)(17)(18)(19). Although biologic agents are expensive and thus increase the direct costs of RA, their inhibitory effects on joint destruction may reduce the need for joint surgery and ultimately offset at least some of the increased direct costs.…”

“…Therefore, we evaluated the impact of TNF blockade on the employability of patients with early-stage RA who participated in the Active-Controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset (ASPIRE) (19).…”

TNFα blockade in human diseases: An overview of efficacy and safety

“…Subsequent clinical trials evaluated whether the combination of a DMARD and an anti-TNFα agent was superior to either agent alone [11,12] or compared an anti-TNF agent with placebo [13,14]. Emboldened by the positive results of these trials, investigators probed a window of opportunity by asking whether treating patients with an anti-TNF agent in early stages (less than 3 years) of disease could 'wipe out' the disease and provide long-lasting remissions [12,[15][16][17].…”

Health Economic Modelling of Treatment Sequences for Rheumatoid Arthritis: A Systematic Review

“…[4] Newer 'biologic' DMARDs (bDMARDs) have had a substantial impact on patient care. The effectiveness of tumor necrosis factor-(TNF-) inhibitors -infliximab, adalimumab and etanercept -has been established in randomised controlled trials (RCTs) [5][6][7][8][9][10][11][12] and confirmed in meta analyses. [13][14][15] More recently, bDMARDs with alternative mechanisms such as rituximab, tocilizumab, and abatacept, along with new TNF-inhibitors -certolizumab pegol and golimumab -have come to market.…”