TNF Inhibitor Therapy for Rheumatoid Arthritis

Abstract

Immunotherapy has improved considerably the treatment outcomes in rheumatoid arthritis (RA). Tumor necrosis factor (TNF)- antagonists have been widely used for the treatment of RA such as infliximab, etanercept, adalimumab and the recent two new TNF- inhibitors -certolizumab pegol and golimumab. Infliximab, a chimeric monoclonal antibody, binds with high affinity and specificity to human TNF and cancels out its biologic activity. Etanercept is also monoclonal antibody, but it is a solute protein. Adalimumab is a recombinant human IgG monoclonal antibody specific for human TNF-. Infliximab, when used in combination with methotrexate (MTX), provides significant, clinically relevant improvement in physical function and quality of life, inhibits the progressive joint damage, and sustains improvement in the signs and symptoms of patients with RA. Etanercept monotherapy is effective and safe for patients with RA. Combination therapy with etanercept and MTX reduces disease activity, decreases total joint score progression, slows the pace of joint destruction, and improves function more effectively than does either monotherapy. Adalimumab with or without MTX also relieves the signs and symptoms of RA. Certolizumab pegol and golimumab expand the therapeutic schedule for patients with RA. All the TNF- inhibitors have similar efficacy in clinical treatment, but they have distinct clinical pharmacokinetic and pharmacodynamic properties that must be considered when selecting a drug for therapy. The common adverse events of these TNF- antagonists include adverse reactions, infections, injection-site reaction and so on. And these adverse events are mostly mild or moderate and the incidence is low. Some patients show a lack of response to anti-TNF- therapies, either due to the lack of drug efficacy or following the development of adverse events. These patients may discontinue the first drug and switch to a second anti-TNF- agent. The shortage of clinical response to one agent may not predict deficiency of response to another. This review mainly addresses the latest development of these biological agents in the treatment of RA, including clinical efficacy, physical function, radiographic progression and adverse events.