Invited Speaker

Tocilizumab, a new therapeutic antibody inhibiting IL-6 action, for immune inflammatory diseases including rheumatoid arthritis and juvenile idiopathic arthritis.
- Mechanisms of action and prediction for the clinical efficacy using DNA microarray -
Norihiro Nishimoto
Japan

Tocilizumab is the first IL-6 inhibitor developed as a therapeutic agent for rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). It was approved for RA and JIA at 2008 April in Japan and for RA at 2009 February in the Europe. Tocilizumab, alone or in combination with disease modifying antirheumatic drugs including methotrexate (MTX), not only dramatically improves arthritis but also retards joint destruction. In the Japanese clinical trial SATORI for RA, 43% of the patients achieved remission defined as disease activity score 28 joints (DAS28) <2.6. IL-6 inhibition by tocilizumab improved serum levels of VEGF, a potent angiogenic factor responsible for the angiogenesis necessary for the hypertrophic synovial tissues of RA and for the increased vascular permeability and inflammation. Interestingly, when serum IL-6 levels were monitored, IL-6 transiently increased in the first 4weeks after starting tocilizumab therapy and then decreased into normal range at 24 weeks in a half of the patients. IL-6 levels well correlated with DAS28 remission and those patients could withdraw from tocilizumab therapy without acute flare. Furthermore, DNA microarray analysis revealed that peripheral blood genes expression profile at the baseline well predicted the clinical response and normalization of serum IL-6. The studies from bedside to bench will be discussed.