Immunobiology of IL-6 — Tocilizumab (humanised anti-IL-6 receptor antibody) for the treatment of rheumatoid arthritis

Yoshiyuki Ohsugi and Tadamitsu Kishimoto

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Abstract

The cloning of IL-6 cDNA in 1986 revealed that IL-6 is a multifunctional cytokine that plays important roles in the immunopathogenesis of rheumatoid arthritis (RA). A close relationship was observed between IL-6 levels in the synovial compartment and disease activity in RA patients, and overproduction of IL-6 could readily explain the abnormal laboratory findings and clinical symptoms seen in these patients. IL-6 therefore appeared to be a worthwhile and attractive therapeutic target for RA. In practice, blockage of IL-6 signalling by a humanised anti-IL-6 receptor antibody [tocilizumab (TCZ); also known as MRA] has been found to be very effective in the treatment of patients with RA. In recent Japanese Phase III clinical studies in RA patients, TCZ clearly prevented radiographic progression of joint destruction and greatly improved signs and symptoms. Very interestingly and importantly, this therapy has also proved quite effective at improving fever, fatigue and anaemia. No serious adverse events have been reported. At present, several international clinical studies of TCZ are ongoing in more than 4000 patients with active RA in 41 countries. The results are continuing to confirm the efficacy and safety of TCZ in the treatment of patients with RA.

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