The safety and efficacy of infliximab in adult patients with RA were assessed in 2 multicenter, randomized, double-blind, pivotal trials: ATTRACT (Study RA I) and ASPIRE (Study RA II). Concurrent use of stable doses of folic acid, oral corticosteroids (≤ 10 mg/day) and/or non-steroidal anti-inflammatory drugs (NSAIDs) was permitted.

Study RA I was a placebo-controlled study of 428 patients with active RA despite treatment with MTX. Patients enrolled had a median age of 54 years, median disease duration of 8.4 years, median swollen and tender joint count of 20 and 31 respectively, and were on a median dose of 15 mg/wk of MTX. Patients received either placebo+MTX or one of 4 doses/schedules of infliximab+MTX: 3 mg/kg or 10 mg/kg of infliximab by IV infusion at Weeks 0, 2 and 6 followed by additional infusions every 4 or 8 weeks in combination with MTX.

Study RA II was a placebo-controlled study of 3 active treatment arms in 1004 MTX naive patients of 3 or fewer years' duration active RA. Patients enrolled had a median age of 51 years with a median disease duration of 0.6 years, median swollen and tender joint count of 19 and 31, respectively, and >80% of patients had baseline joint erosions. At randomization, all patients received MTX (optimized to 20 mg/wk by Week 8) and either placebo, 3 mg/kg or 6 mg/kg infliximab at Weeks 0, 2, and 6 and every 8 weeks thereafter.

Data on use of infliximab products without concurrent MTX are limited [see Adverse Reactions (6.1)].

Clinical Response

In Study RA I, all doses/schedules of infliximab+MTX resulted in improvement in signs and symptoms as measured by the American College of Rheumatology response criteria (ACR 20) with a higher percentage of patients achieving an ACR 20, 50 and 70 compared to placebo+MTX (Table 7). This improvement was observed at Week 2 and maintained through Week 102. Greater effects on each component of the ACR 20 were observed in all patients treated with infliximab+MTX compared to placebo+MTX (Table 8). More patients treated with infliximab reached a major clinical response than placebo-treated patients (Table 7).

In Study RA II, after 54 weeks of treatment, both doses of infliximab+MTX resulted in statistically significantly greater response in signs and symptoms compared to MTX alone as measured by the proportion of patients achieving ACR 20, 50 and 70 responses (Table 7). More patients treated with infliximab reached a major clinical response than placebo-treated patients (Table 7).

Radiographic Response

Structural damage in both hands and feet was assessed radiographically at Week 54 by the change from baseline in the van der Heijde-modified Sharp (vdH-S) score, a composite score of structural damage that measures the number and size of joint erosions and the degree of joint space narrowing in hands/wrists and feet.

In Study RA I, approximately 80% of patients had paired X-ray data at 54 weeks and approximately 70% at 102 weeks. The inhibition of progression of structural damage was observed at 54 weeks (Table 9) and maintained through 102 weeks.

In Study RA II, >90% of patients had at least 2 evaluable X-rays. Inhibition of progression of structural damage was observed at Weeks 30 and 54 (Table 9) in the infliximab+MTX groups compared to MTX alone. Patients treated with infliximab+MTX demonstrated less progression of structural damage compared to MTX alone, whether baseline acute-phase reactants (ESR and CRP) were normal or elevated: patients with elevated baseline acute-phase reactants treated with MTX alone demonstrated a mean progression in vdH-S score of 4.2 units compared to patients treated with infliximab+MTX who demonstrated 0.5 units of progression; patients with normal baseline acute phase reactants treated with MTX alone demonstrated a mean progression in vdH-S score of 1.8 units compared to infliximab+MTX who demonstrated 0.2 units of progression. Of patients receiving infliximab+MTX, 59% had no progression (vdH-S score ≤ 0 unit) of structural damage compared to 45% of patients receiving MTX alone. In a subset of patients who began the study without erosions, infliximab+MTX maintained an erosion-free state at 1 year in a greater proportion of patients than MTX alone, 79% (77/98) vs. 58% (23/40), respectively (P<0.01). Fewer patients in the infliximab+MTX groups (47%) developed erosions in uninvolved joints compared to MTX alone (59%).

Physical Function Response

Physical function and disability were assessed using the Health Assessment Questionnaire (HAQ-DI) and the general health-related quality of life questionnaire SF-36.

In Study RA I, all doses/schedules of infliximab+MTX showed significantly greater improvement from baseline in HAQ-DI and SF-36 physical component summary score averaged over time through Week 54 compared to placebo+MTX, and no worsening in the SF-36 mental component summary score. The median (interquartile range) improvement from baseline to Week 54 in HAQ-DI was 0.1 (-0.1, 0.5) for the placebo+MTX group and 0.4 (0.1, 0.9) for infliximab+MTX (p<0.001). Both HAQ-DI and SF-36 effects were maintained through Week 102. Approximately 80% of patients in all doses/schedules of infliximab+MTX remained in the trial through 102 weeks.

In Study RA II, both infliximab treatment groups showed greater improvement in HAQ-DI from baseline averaged over time through Week 54 compared to MTX alone; 0.7 for infliximab+MTX vs. 0.6 for MTX alone (P ≤ 0.001). No worsening in the SF-36 mental component summary score was observed.