Mode of action

Etanercept is a "designer drug" specifically designed to lower levels of the tumor necrosis factor (TNF), a protein produced by the immune system, which seems to play a major role in causing inflammation as well as joint damage among rheumatoid arthritis patients. It has been discovered that TNF also has a role in causing other chronic health problems, including inflammatory bowel disease and congestive heart failure. Etanercept targets the most common form of the protein, INF-alpha.
In small doses, TNF plays a beneficial role in the immune response by helping the body's cellular repair. However, with rheumatoid arthritis and other disorders of the immune system, too much TNF is produced and it eventually destroys healthy tissue such as the cardiac muscle (congestive heart failure) or the cartilage and bones (rheumatoid arthritis).

In order to damage the cell, TNF must first attach itself to special molecules on the surface of the cell, called TNF-a receptors. Etanercept essentially consists of millions of artificially derived TNF-a receptors. When etanercept is injected into the bloodstream, these TNF-a receptors pick up the INF-alpha which prevents this protein from attaching itself to the cells and therefore prevents the inflammatory reaction.

Help where it is most needed

Etanercept is considered to be a major advance in treating rheumatoid arthritis because it helps the majority of patients who did not benefit from any of the other treatments. It has also shown to be effective in children suffering from the juvenile form of this condition.

Although etanercept is given via injection, it can be taken at home. It is sold in pre-filled syringes (it should be kept in the refrigerator because it is a natural protein that may decompose at room temperature.) At a cost of approximately 85.000 kn ($15.200) a year, etanercept therapy is currently the most expensive of all rheumatoid arthritis treatments.

Side effects

Some patients reported mild injection site reactions and upper respiratory tract infections. Etanercept has showed very few side effects during clinical trials. Nevertheless, some experts have expressed concern that the drug, since it actually shuts down a part of the immune response, may increase the risk of lymphoma and other forms of cancer.

Infliximab

This "designer drug" which has been approved for treating rheumatoid arthritis in 1999, also blocks the action of the tumor necrosis factor, but it works differently than etanercept. Infliximab is composed of millions of identical antibodies, called monoclonal antibodies, which are synthesized in order to target TNF-alpha. Like etanercept, infliximab may lead to significant improvements in patients with rheumatoid arthritis who have not responded to other forms of treatment.

Mode of action

Just as our natural antibodies attach themselves to viruses and bacteria and destroy them, infliximab antibodies attach themselves to the TNF-alpha and deactivate it. This significantly reduces the amount of free TNF-alpha which causes inflammation and joint damage.
Infliximab is given intravenously, by a professional medical worker during a procedure that lasts about 2 hours. It is given every four or eight weeks. One year of infliximab treatment costs about 80.000 kn ($14.300).

According to a study published in April 2000 in the U.S. Journal of Rheumatology, multiple doses of infliximab taken together with methotrexate can achieve long-term suppression of rheumatoid arthritis. In one study conducted on patients in three medical centers, the combination treatment stopped the progression of the disease lasting up to 40 weeks. Most patients showed significant improvement after one or two weeks.

Leflunomide - The tradition of oral medication

If you do not like injections, you will like leflunomide, a DMARD which can be taken orally, usually in tablets of 10, 20 or 100 mg. In fact, it is usually prescribed in an initial "shock" dose of 100 mg per day for the first three days, and after that it is reduced to 20 mg every day. For patients who suffer from side effects the dosage can be reduced to 10 mg per day.

Mode of action

Instead of targeting TNF-alpha, as is the case with the most recent DMARDs, etanercept and infliximab, leflunomide disables lymphocytes, white blood cells that play a role in the immune system's attack on the joints. It accomplishes this by neutralizing an enzyme found in the white blood cells. Research shows that leflunomide is at least as effective as methotrexate in slowing the progress of joint deterioration for patients suffering from rheumatoid arthritis. Equally promising is the fact that 40 to 60 percent of patients respond to the treatment.

Side effects

Since leflunomide is fairly new, there is no data concerning possible long term side effects. Your doctor should conduct frequent tests to monitor its effects on your body, at least during the beginning period of the treatment.

Source: Excerpt from the book "Living with Arthritis"