Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by
joint pain, swelling, stiffness, and progressive destruction of the small joints of the hands and feet. Treatment of RA has improved over the past decade. With multiple
cytokines well-known now to play a role in the pathogenesis of RA, including
tumor necrosis factor alpha,
interleukin (IL)-1β, and
IL-6, many targeted
biological treatments against these
cytokines have emerged, changing the treatment of this disease.
Tocilizumab (TCZ) is a recombinant humanized
monoclonal antibody against the
IL-6 receptor and has been approved in many countries, including the United States, for the treatment of moderate to severe RA in patients who have not adequately responded to one or more
disease-modifying antirheumatic drugs (DMARDs) or cannot tolerate other approved
drug classes for RA. The aim of this review is to discuss the role of
IL-6 in RA, and to provide an overview of the mode of action, pharmacokinetics, and safety of TCZ. Furthermore, efficacy studies of TCZ as both monotherapy and combination
therapy will be evaluated. There have been several important clinical trials evaluating the efficacy and safety of TCZ in RA patients; this review summarizes this data from 14 key trials with emphasis on Phase III trials. Review of these trials provides strong evidence that its use, both as monotherapy and in combination with
methotrexate or other DMARDs, is an effective treatment in reducing the signs and symptoms of RA. TCZ showed tolerable safety but care is required for its use since there are some important safety concerns including elevated liver
enzymes, elevated
low-density lipoprotein,
infections, and gastrointestinal perforations. Additionally, given the efficacy of TCZ in the treatment of RA, this review discusses how TCZ may be beneficial in the treatment of other
autoimmune diseases,
spinal disease,
cardiovascular disease,
organ transplantation, and
malignancies where elevated levels of
IL-6 may play a role in the pathogenesis of these diseases.