Interleukin-6: a new therapeutic target

Abstract

The therapeutic success of biological agents, especially the tumour necrosis factor (TNF) inhibitors, has opened a new chapter in the book of therapies for rheumatoid arthritis. Nevertheless, more than 50% of patients may not respond by > 50% improvement. New compounds have recently entered the treatment arena. One of these is rituximab, which depletes B cells, and another, abatacept, interferes with T-cell co-stimulation. However, although these agents may be effective in a number of patients who fail to respond to TNF blockade, they only rarely induce remission and overall 50% response rates do not exceed those with the TNF inhibitors. Among the major proinflammatory cytokines, IL-6 plays a pleiotropic role both in terms of activating the inflammatory response and osteoclastogenesis. Here, we review recent phase II trials of tocilizumab, a humanized anti-IL-6 receptor antibody that achieves a significant therapeutic response rate.

Figure 1

CHARISMA study design. Four week stabilization on a fixed dose of methotrexate was followed by randomization into seven parallel arms [13]. Intravenous infusions were administered at weeks 0, 4, 8 and 12, and observations were recorded every other week through to 20 weeks. MTX, methotrexate; MRA, tocilizumab. Reproduced, with permission, from [13]. Copyright ^© 2006 American College of Rheumatology.