INTRAVENOUS IMMUNOGLOBULIN IN THE TREATMENT OF POLYARTICULAR JUVENILERHEUMATOID-ARTHRITIS - A PHASE I II STUDY/

Objective. To obtain preliminary information about the safety and effi cacy of intravenous immune globulin (IVIG: Iveegam (R), Immune AG, Vie nna) in the treatment of polyarticular juvenile rheumatoid arthritis ( poly-JRA) resistant to other forms of therapy. Methods. We used a mult icentered, phase I/II blinded-withdrawal design with stratified entry. All patients began by receiving open infusions of IVIG at a dose betw een 1.5 and 2.0 g/kg/infusion (100 g maximum) bimonthly for the first 2 months, then monthly for up to 6 months. Beginning at Month 3, those who met the criteria for ''clinically important improvement'' were ra ndomized to receive monthly infusions for 4 months of either placebo o r IVIG in a double blind (DB) phase. Patients were permitted nonsteroi dal antiinflammatory drugs, slow acting antirheumatic drugs, and low d ose (< 10 mg/day) prednisone at constant doses. An ''early escape'' pr ovision in the DB allowed those who showed ''clinically important wors ening'' to again receive IVIG (if taking placebo) or a higher dose of IVIG (if taking the lower dose of IVIG). Results. Efficacy Twenty-five children entered the trial and 19 (76%) met the criteria for ''clinic al ly important improvement'' during the open phase (OP) and entered t he DB. Three patients completed the OP but failed to meet the criteria for response, and 3 patients dropped out of the OP, none of whom show ed benefit from IVIG. Treatment effect sizes produced by IVIG were; mo derate to large for all variables in the OP. Patients who continued IV IG in the DB continued to show improve ment over that achieved in the OP. Those given placebo showed a rapid loss of efficacy, suggesting IV IG has a limited duration of effect after discontinuation. Safely. No patient developed serious or unexpected adverse side effects in the op en or DB phases, and none dropped out of the study due to toxicity or side effects. Conclusion. Substantial clinical improvement from IVIG i s produced in about three-fourths of patients with poly-JRA during ope n administration, but the duration of the beneficial effect is short a fter discontinuation. Those with disease < 3 years' duration may be mo re likely to respond than those who have had their disease for > 5 yea rs. Short term safety is excellent.