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.
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