This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.This protocol describes a multicenter, randomized clinical trial of two drug regimens in the treatment of polyarticular Juvenile Idiopathic Arthritis (JIA; formerly known as Juvenile Rheumatoid Arthritis, or JRA). This multicenter study of children with JIA, will be carried out at 15 centers (the PI is at Seattle Children's Hospital). There will be 86 subjects nation wide; it is anticipated that there will be 5-8 subjects enrolled at the MMC/Einstein site. Eligible subjects will be those with a diagnosis of JIA by standard criteria. These are new diagnoses: less than 6 months, and no prior biologic or steroid treatment. Patients with significant complicating conditions are excluded, including malignancy, active GI disease, hepatitis.Subjects are randomized to one of 2 treatment arms: methotrexate alone (with placebo etanercept and placebo prednisolone), or methotrexate, etanercept, and prednisolone. Both methotrexate and etanercept are administered through weekly SQ injections; prednisolone is taken orally. All these medications have been in clinical use; they have significant but well-known side effects, and these will be monitored.Children will be screened, informed consent will be obtained (from parents, with appropriate child assent), and they will be seen approximately monthly for a comprehensive evaluation. The evaluations include detailed history, physical exams (including blinded joint exams), routine blood and urine tests, and standardized questionnaires (e.g., QOL measures). They will be carefully assessed for adverse events attributable to study drugs. In addition, a subset of patients (at a subset of centers) will have MRIs of one knee at baseline and at 6 months, for studies to correlate clinical and radiographic findings.Subjects will be evaluated for clinical response after 4 months. Adequate response will be defined as those achieving ACR Pedi 70 - meaning a greater than 70% improvement on at least 3 of 6 key clinical features. Those who do not achieve this outcome will be treated with open label 'triple therapy.' Those who do will continue in the blinded treatment groups until 6 months, when the outcome will be 'Inactive Disease' (ID, as defined by the investigators). Those who achieve on ID continue to the end of the trial; those who do not move to open label therapy. Primary outcomes for analysis include achievement of ID (hypothesis: greater in triple therapy than monotherapy); and differences in safety profile (hypothesis: no difference). There are secondary analyses focused on the outcome of Clinical Remission on Therapy (CRM) and on MRI findings.
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