Remicade - Clinical Pharmacology

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CLINICAL STUDIES

Rheumatoid Arthritis

The safety and efficacy of infliximab were assessed in two 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 was permitted.

Study RA I was a placebo-controlled study of 428 patients with active rheumatoid arthritis 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 REMICADE + MTX: 3 mg/kg or 10 mg/kg of REMICADE 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 three active treatment arms in 1004 MTX naive patients of 3 or fewer years duration active rheumatoid arthritis. 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 REMICADE at weeks 0, 2, and 6 and every 8 weeks thereafter.

Data on use of REMICADE without concurrent MTX are limited (see ADVERSE REACTIONS, Immunogenicity).

for IV Injection Clinical response

In Study RA I, all doses/schedules of REMICADE + 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 1). 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 REMICADE + MTX compared to placebo + MTX (Table 2). More patients treated with REMICADE reached a major clinical response than placebo-treated patients