Trial of Anti-IL-6 Receptor Antibody for Children with So-JIA

Children with the systemic onset form of juvenile idiopathic arthritis (So-JIA) have disease complicated by fever, rash and growth failure. The disease can be extremely hard to bring under satisfactory control in a significant number of these children. Many have had to be kept on very high doses of corticosteroids, which produce profound serious side effects. The disease sometimes progresses to a fatal illness with macrophage activation syndrome.

Studies have shown these children have elevated levels of serum interleukin 6 (IL-6), which may play an important role in causing the clinical symptoms and signs. IL-6 levels rise when the children have severe fever and go down when fever abates.

Yokota, et al, sought to investigate the safety and efficacy of an anti-IL-6 receptor antibody (MRA) that was recently developed. MRA prevents the formation of the IL-6/IL-6R complex and inhibits the function of IL-6 in children with So-JIA. They undertook a preliminary dosing phase II trial of humanized monoclonal antibody to the IL-6 receptor to block So-JIA in 11 children. IV doses, starting at 2 mg/kg per week were adjusted to 2 to 8 mg/kg per week or every other week[1].

In this study of 11 patients, blocking the IL-6 receptor caused prompt reduction in fever and rash and many of the laboratory markers of inflammation improved as well. The 70% JIA core set response was achieved in 7 children by two weeks after the first dose. Others achieved significant improvement as their dose was raised. These results were very exciting, demonstrating the ability of MRA to control symptoms of So-JIA.

Although no child withdrew because of disease flare or adverse events, infections were a major concern. Dr. Yokota emphasized that 6 of the 11 patients had infections, and that 3 of 6 patients in his previously reported phase 1 study also developed infections. This high level of infectious complications may prove very troublesome in attempting to make this an appropriate therapy to be routinely used in the treatment of patients.

Nonetheless, the children in these studies had already failed methotrexate and cyclosporine. Other investigators have been using thalidomide, adalimumab, and cyclophosphamide to treat severe So-JIA with varying results. Until we find one therapy that works for all these children, it's important to try to find the safest effective therapy on many fronts..