Rheumatoid arthritis - MRA
Rheumatoid arthritis is an autoimmune disorder affecting an estimated 6m people around the world. It is characterised by symmetric joint inflammation with erosive synovitis, and its cause is unknown.
Most sufferers experience a chronic fluctuating course of disease, with pain and joint swelling, particularly in the fingers, wrists, ankles and feet, and also the hips, neck, knees and shoulders as the disease progresses. Even if treated, there is often progressive joint destruction, ultimately resulting in a loss in function of the joints.
Standard drug therapy is with NSAIDs, steroids and methotrexate, and surgical intervention can be required as the disease progresses. A new treatment being developed by Chugai, and licensed to Roche, is the monoclonal antibody MRA. It is a humanised antihuman interleukin-6 receptor monoclonal antibody, and has been developed in conjunction with Osaka University in Japan.
Interleukin-6 (IL-6) is a pleiotropic cytokine that has a broad range of biological actions. A continuous overproduction of IL-6 is seen in patients with immune inflammatory diseases such as rheumatoid arthritis, and successful treatment of model animals for immune inflammatory diseases with anti IL-6 receptor antibodies suggested that it might be a successful strategy for treating humans.1
To investigate the safety and efficiency of MRA, a randomised double blind placebo-controlled dose escalation trial was carried out in 45 patients with active rheumatoid arthritis.2 The patients were sequentially allocated to receive a single intravenous dose of 0.1, 1, 5 or 10mg/kg of MRA, or placebo. After two weeks, a significant treatment difference was seen between those given 5mg/kg of the active and the placebo, with over half of those given MRA seeing at least 20% improvement in their symptoms. There were no serious adverse events that were believed to be related to the drug. And fewer patients given the higher doses needed corticosteroid or disease modifying antirheumatic drug treatment because of active disease before the end of the study.
Phase III studies are due to start soon. The antibody is also being investigated for other autoimmune disorders, including Castleman's disease, juvenile idiopathic arthritis, Crohn's disease, and multiple myeloma.