Abstract
Tumor necrosis factor (TNF)-α is a potent pro-inflammatory and pathological cytokines in inflammatory diseases such as rheumatoid arthritis and inflammatory bowel diseases. Anti-TNF-α therapy has been established as an efficacious therapeutic strategy in these diseases. In clinical settings, three monoclonal anti-TNF-α full IgG1 antibodies infliximab, adalimumab, and golimumab, PEGylated Fab' fragment of anti-TNF-α antibody certolizumab pegol, extracellular domain of TNF receptor 2/IgG1-Fc fusion protein etanercept, are almost equally effective for rheumatoid arthritis. Although monoclonal full IgG1 antibodies are able to induce clinical and endoscopic remission in inflammatory bowel diseases, certolizumab pegol without Fc portion has been shown to be less effective for inflammatory bowel diseases compared to full IgG1 antibodies. In addition, there are no evidences that etanercept leads clinical remission in inflammatory bowel diseases. Besides the common effect of anti-TNF-α agents on neutralization of soluble TNF-α, each anti-TNF-α agent has its own distinctive pharmacological properties which cause the difference in clinical efficacies. Here we focus on the distinctions of action of anti-TNF-α agents especially in following points; (1) blocking ability against ligands, transmembrane TNF-α and lymphotoxin, (2) effects toward transmembrane TNF-α-expressing cells, (3) effects toward Fcγ receptor-expressing cells, (4) degradation and distribution in inflamed tissue. Accumulating evidence will give us the idea how to modify anti-TNF-α agents to enhance the clinical efficacy in inflammatory diseases.
Keywords:
Anti-TNF-α therapy; Inflammatory bowel disease; Rheumatoid arthritis; Tumor necrosis factor-α.
Copyright © 2016 Elsevier Ltd. All rights reserved.
MeSH terms
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Adalimumab / adverse effects
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Adalimumab / genetics
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Adalimumab / therapeutic use
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Animals
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Anti-Inflammatory Agents / administration & dosage
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Anti-Inflammatory Agents / adverse effects
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Anti-Inflammatory Agents / therapeutic use
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Antibodies, Monoclonal / adverse effects
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Antibodies, Monoclonal / genetics
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Antibodies, Monoclonal / therapeutic use
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Antibodies, Monoclonal, Humanized / administration & dosage
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Antibodies, Monoclonal, Humanized / adverse effects*
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Antibodies, Monoclonal, Humanized / genetics*
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Antibodies, Monoclonal, Humanized / therapeutic use
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Antirheumatic Agents / administration & dosage
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Antirheumatic Agents / adverse effects
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Antirheumatic Agents / therapeutic use
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Arthritis, Rheumatoid / drug therapy*
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Arthritis, Rheumatoid / immunology
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Certolizumab Pegol / adverse effects
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Certolizumab Pegol / genetics
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Certolizumab Pegol / therapeutic use
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Disease Models, Animal
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Etanercept / adverse effects
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Etanercept / therapeutic use
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Humans
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Immunoglobulin Fab Fragments / adverse effects
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Immunoglobulin Fab Fragments / genetics
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Immunoglobulin Fab Fragments / therapeutic use
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Immunoglobulin G / adverse effects
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Immunoglobulin G / genetics
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Immunoglobulin G / therapeutic use*
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Immunologic Factors / adverse effects
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Immunologic Factors / genetics
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Immunologic Factors / therapeutic use
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Immunosuppressive Agents / administration & dosage
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Immunosuppressive Agents / adverse effects
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Immunosuppressive Agents / therapeutic use
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Inflammatory Bowel Diseases / drug therapy*
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Inflammatory Bowel Diseases / immunology
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Infliximab / adverse effects
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Infliximab / genetics
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Infliximab / therapeutic use
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Mice
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Polyethylene Glycols / therapeutic use
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Tumor Necrosis Factor-alpha / antagonists & inhibitors*
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Tumor Necrosis Factor-alpha / immunology
Substances
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Anti-Inflammatory Agents
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Humanized
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Antirheumatic Agents
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Immunoglobulin Fab Fragments
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Immunoglobulin G
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Immunologic Factors
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Immunosuppressive Agents
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Tumor Necrosis Factor-alpha
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Polyethylene Glycols
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golimumab
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Infliximab
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Adalimumab
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Etanercept
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Certolizumab Pegol