Doctors investigating what takes place in the body during the progression of psoriatic arthritis (PsA) have discovered that a specific protein called tumor necrosis factor-alpha (TNF-alpha) plays a central role. Tumor necrosis factor-alpha is involved in the body's inflammatory process and has been linked to several chronic inflammatory conditions, including rheumatoid arthritis. In recent years, doctors have found evidence that TNF-alpha is also linked to psoriatic arthritis, and it is presently considered to be an important indicator of the disease. High concentrations of TNF-alpha can be found in the skin, in blister fluid and in the synovial fluid that lines the joints of patients with psoriatic arthritis,. Fortunately, doctors have discovered that the more TNF-alpha present, the more severe the damage from the disease is likely to be.
How the Immune System Works
Tumor necrosis factor-alpha is produced naturally in the body by multiple cells. In a normal immune system, it works together with other cells, tissues and organs to protect the body from infection and disease. The immune system cells do this by identifying and attacking foreign substances, such as bacteria, viruses, parasites and fungi.
When a foreign substance, also known as an antigen, is present, it activates a specific type of white blood cell called a T-cell. These cells, considered by many to be the "generals" of the immune system, are in charge of coordinating the immune response which will neutralize a foreign substance.
One part of this response includes the release of interleukins, which are types of cytokines or nonantibody proteins that the immune system uses to communicate messages. One of these cytokines is TNF-alpha.
A healthy immune system can clear itself of TNF-alpha, but in psoriatic arthritis, something happens to activate the T-cells to work overtime. As a result, they begin acting as if they are fighting off an infection, which in turn, signals the production of an excess amount of TNF-alpha. As TNF-alpha builds up, the messages it communicates create a cascade of events, which send more and more T-cells to the affected area.
In psoriasis, the result is the rapid growth of skin cells. Skin cells can grow up to 10 times faster than normal in people with psoriasis. When this occurs, the cells pile up at the skin's surface and lesions form. In psoriatic arthritis, the overproduction of TNF-alpha and the mixed messages it communicates results in joint inflammation, which usually produces joint pain and stiffness, tissue damage and other symptoms associated with psoriatic arthritis.
New Drugs Inhibit Tumor Necrosis Factor-Alpha
One of the most promising treatment options for psoriatic arthritis is a class of medications called biologic response modifiers, which have been specifically designed to target the TNF-alpha protein. They have been used successfully in the treatment of rheumatoid arthritis, and as rheumatologists become more familiar with biologic response modifiers, they have begun to recommend them for the treatment of psoriasis and psoriatic arthritis.
Health
Biologics, as they are often referred to, are the newest class of drugs on the market designed to treat psoriatic arthritis, and they are considered by many to be the most promising. In addition to halting the inflammation caused by the disease, studies have shown that they can improve quality of life of a patient with psoriatic arthritis. Studies also indicate that they may slow down, and in some cases halt, the progression of both psoriatic arthritis and psoriasis.
Made from animal proteins, biologics work by binding to TNF-alpha and preventing it from communicating with other cells. By blocking the action of the TNF-alpha cells, the drugs halt the inflammatory damage caused by psoriatic arthritis.
There are several biologic medications available now that are approved for the treatment of psoriasis and psoriatic arthritis. They include adalimumab (Humira®), alefacept (Amevive®), efalizumab (Raptiva®), etanercept (Enbrel®) and infliximab recombinant (Remicade®); of these only Humira, Enbrel and Remicade are approved for the treatment of psoriatic arthritis.
These TNF-alpha blocking agents cannot cure psoriasis and psoriatic arthritis, but they have been proven effective, in varying degrees, at treating the conditions. Some of the biologics work by decreasing the number of cells in the skin and blood. Other biologics work by blocking the activation of the immune cells or by blocking the psoriasis-causing chemicals that are released by them. In either event, they are capable of reducing inflammation and other signs and symptoms. Since biologics target the specific mechanism in the immune system that causes inflammation, they are thought to spare the body from the potentially serious side effects that have been associated with other treatments for psoriatic arthritis.
There are, however, several reasons why biologics are not considered an appropriate treatment for everyone. Firstly, they are given by injection, either at home or in a physician's office. Secondly, they are prohibitively expensive due to the complexity of their development—the annual costs can be over $12,000.
These drugs have not been proven effective for all patients, and they carry their own set of risks. Short-term side effects include an allergic reaction at the site of the injection, but the long-term effects can be graver. Recent evidence suggests that biologics may increase a patient's risk for serious infections, such as tuberculosis and cancer, especially of the blood or lymphatic system. For these reasons, care is taken to recommend them for use in patients who have not responded to more conventional treatments or who have experienced side effects as a result of other medications.
