Tocilizumab: The First Interleukin-6-Receptor Inhibitor

Anthony Sebba, M.D.


Am J Health Syst Pharm. 2008;65(15):1413-1418. 

In This Article

Abstract and Introduction

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.

Rheumatoid arthritis (RA) is an autoimmune disease characterized clinically by bilateral symmetrical inflammation of the small joints of the hands, feet, and other peripheral joints, with potential for joint destruction.[1,2] RA is also associated with systemic symptoms such as fatigue,[3] heart disease,[4,5] anemia,[6] and elevation of acute-phase reactants, such as C-reactive protein (CRP).[7] In the past decade, there have been several therapeutic advances in the treatment of RA, as biological therapies targeting specific elements of the immune response have become increasingly available ( Table 1 ).[14,15] Tocilizumab is a humanized anti-interleukin-6-receptor (IL-6R) monoclonal antibody (mAb) that inhibits interleukin-6 (IL-6) signaling.[16] This new biological agent is in clinical development for the treatment of inflammatory autoimmune diseases such as RA and systemic onset juvenile idiopathic arthritis, in which IL-6 inhibition appears to provide both local and systemic benefits.

This article reviews the concept of IL-6R inhibition with tocilizumab to acquaint pharmacists with the properties of this new agent.


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