Infliximab is a monoclonal antibody that is administered intravenously to treat patients with chronic inflammatory diseases including Crohn’s disease, ulcerative colitis, rheumatoid arthritis, plaque psoriasis, psoriatic arthritis, and a form of arthritis that affects the spine called ankylosing spondylitis.
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Treatment with infliximab
The intravenous (IV) infusion of infliximab is administered over a two-hour period, followed by additional infusions two and six weeks later. Depending on the condition being treated and how well a patient responds, infliximab is then administered as a part of a maintenance program, at intervals of six to eight weeks.
Clinical indications
In arthritic conditions, infliximab reduces the movement of inflammatory cells into inflamed parts of the joints, which reduces the signs and symptoms of the condition, improves physical function, decreases joint damage, and reduces the level of other inflammatory markers.
In the case of Crohn’s disease and ulcerative colitis, infliximab decreases the movement of inflammatory cells into inflamed parts of the intestine. When used for the treatment of ulcerative colitis, this drug also promotes the healing of ulcers in the intestinal wall.
Comparatively, when infliximab is used to treat plaque psoriasis, it reduces inflammation of the skin and the thick scaly skin plaques the condition causes.
Infliximab and TNF-α
Monoclonal antibodies are specifically designed to bind to unique proteins in the body. Infliximab works by specifically binding to and inhibiting the activity of a protein called TNF-α (tumor necrosis factor-alpha).
TNF-α is an important protein made by cells as part of the body’s immune response to infection. In the case of inflammatory diseases, excessive production of TNF-α can lead to inflammation that damages the bones, cartilage, and other tissues. Infliximab blocks the action of TNF-α, which suppresses the immune system, thereby reducing inflammation and related symptoms.
Mechanism
Infliximab inhibits TNF-α activity by binding to transmembrane and soluble forms of the protein, as well as by preventing TNF-α from binding to its receptor. The biological activities of TNF-α include the induction of the cytokines involved in inflammation such as interleukin-1 (IL-1) and IL-6, promotion of leukocyte migration, induction of eosinophil and neutrophil activity, as well as the stimulation of acute-phase reactants and tissue degrading enzymes.
Treatment with infliximab neutralizes these functional activities of TNF-α, leading to an overall reduction in inflammation. Infliximab therapy reduces the production of IL-1 and IL-6, thus limiting leukocyte migration and reducing adhesion molecule expression by leukocytes and endothelial cells.
Infliximab also limits the biological activity of eosinophils and neutrophils, as well as reduces the production of degrading enzymes made by chondrocytes and synoviocytes. Infliximab decreases synovitis and joint damage in arthritis and promotes the healing of eroded joints.
Adverse effects
The use of anti-TNF therapy is associated with a range of side effects, which are usually the result of the drug’s immunosuppressant activity. TNF is an important cytokine in the immune response to tuberculosis; therefore, TNF inhibitors can lead to the reactivation of a latent TB infection.
Other adverse effects can include histoplasmosis and other fungal infections, neurological events, congestive heart failure, cancer, and autoimmunity.
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