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Targeting of Interleukin-6 for the Treatment of Rheumatoid Arthritis: A Review and Update

Toshio Tanaka, Atsushi Ogata and Tadamitsu Kishimoto

Rheumatoid Arthritis (RA) is a chronic inflammatory disease, characterized by persistent joint inflammation, systemic inflammation and immunological abnormalities. Since IL-6 plays a major role in the development of these characteristics, its targeting could reasonably be expected to constitute a novel therapeutic strategy for the treatment of RA. Tocilizumab, a humanized anti-human IL-6 receptor monoclonal antibody, has demonstrated its outstanding clinical efficacy and tolerable safety profile in phase III clinical trials for RA patients, resulting in its worldwide approval for moderate-to-severe active RA. Post-marketing clinical trials have confirmed its efficacy. This success led to the development of various other IL-6 inhibitors. Further clinical studies including head-to-head comparative studies, and clarification of the mechanisms through which tocilizumab exerts its clinical effects can be expected to identify RA patients who should be treated with tocilizumab as a first-line biologic. In addition, recent case reports and pilot studies indicate that therapies targeting IL-6 will be widely applicable to the treatment of various intractable immune-mediated diseases.