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ANTHONY SEBBA, M.D., is Assistant Clinical Professor, University of South Florida, 36338 U.S. Highway 19 North, Palm Harbor, FL 34684-1528 (asebba{at}tampabay.rr.com).

Purpose. The pharmacology, pharmacokinetics, clinical efficacy, safety, and role of tocilizumab in rheumatoid arthritis (RA) are reviewed. Summary. Tocilizumab is a novel monoclonal antibody that competitively inhibits the binding of interleukin-6 (IL-6) to its receptor (IL-6R). Inhibiting the entire receptor complex prevents IL-6 signal transduction to inflammatory mediators that summon B and T cells. Tocilizumab has a nonlinear pharmacokinetic profile. The hypothesis that targeting and inhibiting IL-6R with tocilizumab can result in significant improvement of the signs and symptoms of RA appears to have been substantiated in one Phase III and two Phase II clinical trials, which have demonstrated a marked reduction in disease activity and the acute-phase response. The results of these studies indicate that tocilizumab treatment, both as a combination with methotrexate and as monotherapy, has a safety profile consistent with that of other biological and immunosuppressive therapies. In general, tocilizumab as monotherapy and in combination with methotrexate appears to be well tolerated. Adverse events were not dose dependent and were of similar frequency in all groups. Tocilizumab appears to provide an additional option for those patients who do not respond sufficiently to methotrexate. Since IL-6R inhibition has a distinct mechanism of action, some patients who do not respond to antitumor necrosis factor agents or who have a partial response may respond to tocilizumab. Conclusion. Tocilizumab, a novel IL-6R inhibitor, may be beneficial for the treatment of RA in patients who do not respond to methotrexate or disease-modifying antirheumatic drugs. A large clinical trial is needed to confirm tocilizumab’s clinical efficacy and safety. Index terms: Antibodies; Arthritis; Mechanism of action; Pharmacokinetics; Tocilizumab; Toxicity