Monoclonal Antibody Treatment for Systemic Lupus Erythematosus

Interleukin-6 (IL-6) levels are elevated in both human and murine systemic lupus erythematosus (SLE). Blocking the action of IL-6 ameliorates disease activity in murine models of SLE. MRA is a humanized monoclonal antibody against the human IL-6 receptor. Data from clinical trials in patients with rheumatoid arthritis suggest that MRA may be a safe agent to block the effect of IL-6 and therefore may be used to evaluate the effects of IL-6 blockade in patients with SLE. In this open label, dose-escalating, Phase I study, up to 27 subjects with moderately active SLE may be enrolled. Subjects will be treated with bi-weekly infusions of one of three doses (2mg/kg, 4 mg/kg or 8 mg/kg) of MRA for 12 weeks and followed for 8 weeks after the last dose. Patients with or without lupus nephritis may be enrolled if they do not require immediate immunosuppressive therapy other than prednisone at doses of less than or equal to 0.3 mg/kg/day. Safety will be evaluated using standard clinical and laboratory parameters. To assess the potential effect of MRA on SLE, clinical and laboratory evaluations and surrogate markers of inflammation and disease activity, such as autoantibody production and lymphocyte subsets, will be compared before and after the treatment. Patients who either do not tolerate the drug or those who have a clinically significant increase in their disease activity that does not respond to moderate doses of corticosteroids will be withdrawn from the protocol. If this regimen is shown to be well tolerated, studies of efficacy will be planned. This agent is expected to be devoid of the most common toxicities of therapies commonly used in the treatment of SLE, such as myelosuppression, amenorrhea and osteoporosis. This study will provide important preliminary information about the safety and possible effect of IL-6 blockade in SLE patients, an intervention that has been successful in animal models but has not yet been studied in humans.