Review of Tumor Necrosis Factor Inhibitors on Rheumatoid Arthritis

Jung-Soo Song

doi:10.4078/jkra.2007.14.1.1

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Song: Review of Tumor Necrosis Factor Inhibitors on Rheumatoid Arthritis

Original Article

J Korean Rheum Assoc 2007;14(1):1-14.

Published online: 23 March 2007

DOI: https://doi.org/10.4078/jkra.2007.14.1.1

Review of Tumor Necrosis Factor Inhibitors on Rheumatoid Arthritis

Jung-Soo Song, M.D., Ph.D.

Division of Rheumatology, Department of Internal Medicine, Chung-Ang University School of Medicine, Seoul, Korea

Received 19 January 200715 April 2007

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Advanced knowledges of cellular and molecular biology led to the development of therapies of rheumatoid arthritis (RA). The introduction of biologic agents into clinical practice has had a profound effect on the current management of RA. These agents can rapidly enhance functional status and inhibit the progression of joint damage from the disease.

Tumor necrosis factor (TNF) inhibitors are the representative biologic agents for the treatment of RA. Their clinical efficacy and safety were revealed through many clinical trails. Novel TNF inhibitors and other biologic agents for the treatment of RA are developing continuously. Promising biologic agents such as TNF inhibitors have become an important part of treatment armamentarium for RA, although they have some side effects and problems to be solved. These agents may contribute to achieve the sustained remission and eventually cure of RA. Currently available TNF inhibitors in Korea include etanercept, infliximab and adalimumab.

This review article introduces past, present, and future of the TNF inhibitors and suggests guidelines for the proper use of them on RA.

Keywords: Rheumatoid arthritis, Treatment, Tumor necrosis factor inhibitors, Biologic agents

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Fig. 1.

Key cytokines in rheumatoid arthritis.

Table 1.

Biological interventions investigated in rheumatoid arthritis

Cell surface-directed therapy

Anti-CD3 mAb, anti-CD4 mAb, anti-CD5 mAb,

anti-CD7 mAb, anti-CD20 mAb (rituximab),

anti-CD25 mAb, anti-CD28 mAb, anti-CD52

mAb, IL2 fusion protein, anti-ICAM-1, CTLA-4Ig

(CD86 binding)

Cytokine targeted therapy

TNF antagonists (mAb, soluble TNF receptor)

IL-1 receptor antagonist

IL-6 antagonist (mAb against IL-6 or IL-6 receptor)

Administration of cytokines (IL-4, IL-10, IFN, and

IFN- β)

Tolerance induction

Application of antigens (collagen II, HCGP-39)

T cell or T cell receptor vaccination

Interference with T cell activation (CTLA-4Ig)

Inhibition of chemokines

Inhibition of complement activation

High dose intravenous immunoglobulins

Plasmapheresis, immunoadsorption column

Autologous bone marrow transplantation

CTLA-4: cytotoxic T lymphocyte antigen-4, ICAM: intracellular adhesion molecule, IFN: interferon, Ig: immunoglobulin, IL: interleukin, mAb: monoclonal antibody, TNF: tumor necrosis factor

Table 2.

Characteristics of TNF inhibitors for treating rheumatoid arthritis

Agent	Specificity	Structure	Mechanism of action	Half-life
Etanercept	Soluble and membrane-bound TNF and lymphotoxin- α	Dimeric fusion protein: human TNF receptor connected to Fc portion of human IgG1	Binds soluble and cell-bound TNF, thereby inhibiting the interaction of TNF with cell-surface TNF receptors	4 days
Infliximab	Soluble and membrane-bound TNF	Chimeric mouse/human monoclonal antibody to TNF	Binds soluble and cell-bound TNF, thereby preventing interaction with cell-surface TNF receptors	8-9.5 days
Adalimumab	Soluble TNF	Human monoclonal antibody to TNF	Binds TNF, thereby preventing interaction with cell-surface TNF receptors	11 —13.7 days

TNF: tumor necrosis factor, Fc: constant region fragment, IgG1: immunoglobulin G1

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