Anti-interleukin-6 receptor antibody treatment in inflammatory autoimmune diseases.
Tocilizumab (namely MRA), a humanized anti-interleukin (IL)-6 receptor monoclonal antibody, is under development by Roche for the treatment of inflammatory autoimmune diseases such as rheumatoid arthritis (RA), systemic onset juvenile idiopathic arthritis (JIA), adult-onset Still's disease, Castleman's disease and Crohn's disease. Tocilizumab has a long plasma half-life, so it can be administered intravenously biweekly or monthly. Phase I and II clinical trials showed that tocilizumab (2, 4, 5, 8 or 10 mg/kg) reduced disease activity significantly in a dose-dependent manner. Tocilizumab not only improved signs and symptoms, but also normalized inflammatory markers such as C-reactive protein, erythrocyte sedimentation rate (ESR), fibrinogen and serum amyloid A, and reversed joint damage of RA. The efficacy of tocilizumab in the treatment of RA was at least as good as methotrexate. Tocilizumab was generally safe and well tolerated. Some adverse events such as significant rises in total cholesterol and triglyceride levels, liver function disorders, decreases in white blood cell counts, diarrhoea and infection were observed. In summary, preliminary clinical results suggest that tocilizumab is effective and generally well tolerated in the treatment of IL-6-related inflammatory autoimmune diseases. Like other anti-cytokine immunotherapies, caution and close monitoring for the adverse events, especially infection, are necessary in subsequent clinical trials.
Ding
Changhai
C
Menzies Research Institute, Hobart, Tasmania, Australia. changhai.ding@utas.edu.au
Jones
Graeme
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001171:Arthritis, Juvenile / Q000188:drug therapy; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D005871:Castleman Disease / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D003424:Crohn Disease / Q000188:drug therapy; D004195:Disease Models, Animal; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy; D016706:Still's Disease, Adult-Onset / Q000188:drug therapy; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015850:Interleukin-6; C502936:tocilizumab