Infliximab to Treat Children With Juvenile Rheumatoid Arthritis

Infliximab, a murine chimeric monoclonal antibody targeted against TNF-alpha has recently been licensed for the treatment of adult patients with established rheumatoid arthritis (RA). A double blind placebo controlled trial in children with juvenile rheumatoid arthritis (JRA) using a single dose fixed infusion regimen is currently ongoing. This dose finding study is designed to determine whether a clinically guided intravenous (iv) infusion regimen allowing for intra-patient dose escalation is superior in achieving a 70% clinical response to fixed dose administration of infliximab in children with a polyarticular course of JRA. We will model the pharmacokinetic profile in both phases of the study. We plan to enroll a maximum of 48 patients to allow for 36 patients to be randomized into the two treatment arms. In the first phase of the study all patients will receive a fixed dose of 5mg/kg/dose for a total of 3 infusions over 6 weeks (weeks 0, 2, 6). In the second phase at week 14, patients who have not achieved a 70% improvement will be randomized at a 2:1 ratio to either receive intra-patient dose escalation capped at 15mg/kg/dose every 8 weeks or continue to receive 5mg/kg/dose every 8 weeks in a blinded fashion. After 6 additional IV doses, patients will again be evaluated clinically, radiographically and serologically for clinical response. Patients who achieved a 70% response by week 14 will be kept on 5mg/kg/dose every 8 weeks for the trial duration of 62 weeks, but will not be included in the primary endpoint analysis. We also plan to evaluate patients endocrinologically and metabolically to determine the effect of TNF blockade on these systems.