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The most important recent advance in the treatment of rheumatoid arthritis (RA) has been the development of drugs called biologic response modifiers. They are a subset of the class of drugs known as disease modifying antirheumatic drugs or DMARDs. However, instead of affecting the entire immune system as the traditional DMARDs do, these sophisticated drugs zero in on a specific component of the immune system. As a result of this approach, they have been proven to work faster and without the side effects associated with other DMARDs. They have also been proven to be effective at stopping the progressive joint damage associated with rheumatoid arthritis.

Biologics are derived from living or synthetic organisms. Some of the biologics currently in use to treat rheumatoid arthritis target a specific component of the immune system called cytokines. These proteins play a pivotal role in the inflammatory process. Three of these drugs block a cytokine in the joints called tumor necrosis factor alpha (TNF-alpha), which is a known cause of inflammation, fever, pain, tenderness and swelling—all symptoms common to rheumatoid arthritis and other inflammatory conditions. By blocking TNF-alpha, the drugs help reduce inflammation and the resulting structural damage to the joints. This, in turn, improves patients’ quality of life by improving their mobility and function.

Specific Therapies
The following TNF-alpha blockers are approved for the treatment of rheumatoid arthritis. Enbrel® (entercept) is a synthetic, man-made protein that binds to TNF-alpha and acts like a sponge to remove the TNF-alpha molecules from the joints and blood. It has proven effective at preventing the progressive destruction of the joints in patients with rheumatoid arthritis. It is often prescribed when patients have not responded to other drugs. It is commonly given alone or in combination with methotrexate.

Enbrel is given by self-injection once or twice per week. Studies show it may cause irritation at the injection site. Other common side effects include headache, dizziness and nasal and throat irritation.

Because the drug weakens the immune system, patients with serious infections should not take Enbrel. In addition, research conducted since it was approved by the U.S. Food and Drug Administration in 1998 shows that in rare circumstances the medication has been associated with severe and sometimes fatal blood disorders or the worsening of existing blood disorders.

There have also been reports linking Enbrel to multiple sclerosis and optic neuritis or inflammation of the optical nerve. Reports of an increased risk of congestive heart failure have prompted doctors to use caution if patients have already been diagnosed with the condition.

Remicade® (infliximab) also reduces inflammation in patients with rheumatoid arthritis by blocking the TNF-alpha molecule. It is a monoclonal antibody derived from human and mouse genes. It was approved by the U.S. Food and Drug Administration in 1999.

Remicade is given by intravenous infusion in the doctor's office or hospital. Each infusion takes about 2 hours. The intravenous treatments are given three times during the first six weeks of therapy and after that, every eight weeks. It is typically given alone or in combination with other DMARDs, like methotrexate, to increase the therapeutic benefits and limit the side effects.

Like Enbrel, treatments with Remicade may weaken the body's ability to fight infection. Patients are encouraged to see their doctor if signs of infection such as fever, sweats, chills, skin rash or other symptoms are present.

Research conducted since the U.S. Food and Drug Administration’s approval shows there may be a link between Remicade and an increased risk of cancer or lymphoma. However, since patients with rheumatoid arthritis have a higher risk of lymphoma than the general population, this link has not been confirmed. Patients with congestive heart failure should not use Remicade.

Humira® (adalimumab), the newest TNF-alpha blocker, was approved for the treatment of rheumatoid arthritis in 2002. Like Enbrel, it is a synthetic, man-made protein that slows the progressive destruction of the joints and improves physical function in moderate to severe cases of rheumatoid arthritis. It is a self-administered injection taken once every two weeks and can also be used alone or in combination with other medications.

Doctors have reported rare cases of severe allergic reactions including difficulty with breathing, hives and itching. A weak or rapid pulse and blood cell deficiencies have also occurred. Bruising or bleeding can be a sign of blood cell problems and should be reported to a physician.

Serious infections have been seen in clinical trials when Humira was taken with another rheumatoid arthritis drug named Kineret® (anakinra). It has also been associated with serious infections such as tuberculosis, sepsis and fungal infections. Humira may worsen the symptoms of central nervous system diseases like multiple sclerosis.

Regular Monitoring Is Important
Because biologic medications suppress the immune system, they can make patients more susceptible to other infections and diseases. In fact, the most significant side effect of these medications is an increased risk of all types of infections, including tuberculosis. That is why doctors will administer a tuberculosis test before starting a patient on a TNF-alpha blocker. For the same reason, these medications should be stopped when an active infection is present, or if an antibiotic is required. Similarly, patients should seek immediate medical attention if they develop a persistent fever.

Biologics may cause certain chronic diseases in remission to flare up, and they are often not recommended for people with multiple sclerosis and other conditions. A link has also been suggested between some biologics and cancer. However, since patients with rheumatoid arthritis have a higher rate of cancers than the general population, the connection between cancer remains unclear and under investigation.

Much about these drugs remains under investigation, since they have only been in use for only a few years. Their long-term effects remain unknown, and continue to be reviewed. Regular monitoring by a physician, including periodic blood tests and other tests, may be needed to determine the effectiveness of the treatment and the presence of any side effects.

Biologics Are Not for Everyone
Finally, it is important to remember that biologic medicines are not for everyone. How well they work varies from person to person. In some people, they may not work at all. For others, one biologic may not work but another may be effective. Biologics are also much more expensive than what are considered to be conventional treatments for rheumatoid arthritis. Treatment can cost at least $10,000 and often more per year. Their cost and the lack of insurance reimbursement may limit their availability for some patients.