TNF-α blocking agents

TNF-α blocking agents

TNF-α (tumor necrosis factor) is an important cytokine in the inflammatory reaction of rheumatoid arthritis and is produced by a number of inflammatory cells (monocytes, macrophages, B and T cells, and fibroblasts). Levels of tumor necrosis factor, as well as tumor necrosis factor receptors, are elevated in the synovial fluid of rheumatoid arthritis patients. Binding of TNF-α to its receptor results in damage to the cartilage and bone, invasion of lymphocytes from the small blood vessels, and secretion of inflammatory factors by many cell types. Until now, three drugs which inhibit the biological activity of TNF-α has been developed and are prescribed to treat RA. They are expensive and their long term effects are not yet known.

Etanercept is a human TNF-α receptor p 75 Fc fusion protein produced via recombinant DNA technology. It binds with high specificity to TNF-α and thus prevents its biological activity. Etanercept is given twice a week in fixed dose by subcutaneous injection. General side effects have included fever, headache, flu syndrome, and weight gain. Other side effects of etanercept include skin reactions at the site of injection and increased susceptibility to infections such as tuberculosis.

Adalimumab is a fully human monoclonal antibody which is given by subcutaneous injections once in 2 weeks in a fixed dose. Side effects are very much the same as in etanercept.


Infliximab is a chimeric human-mouse monoclonal antibody with high affinity for TNF-α. By binding TNF-α, infliximab prevents its stimulatory action at the receptor site and subsequent activity in the inflammatory reaction. Infliximab is given by intravenous infusion and the dosage varies between 3-10 mg/kg every 2 months. Infliximab is mostly used in combination with methotrexate to prevent the formation of antibodies to infliximab, which can diminish the effectivity. Side effects resemble those of etanercept. Since infliximab is an antibody derived from a mouse, allergic reactions can occur directly after infusion.

Close monitoring of the effects and side effects of TNF-α blocking agents is necessary. Patients should be asked for infections, and if present, these must be treated aggressively and the anti-TNF treatment should sometimes be discontinued for a while. Furthermore, bone marrow function and liver enzymes need to be monitored.




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