Rheumatoid Arthritis

by Food and Drug Administration (FDA)

(Page 2 of 3)

Typical treatments for rheumatoid arthritis have relied on a combination of NSAIDs, such as ibuprofen or aspirin (which reduce swelling and alleviate pain but do not change the course of the disease) and disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate and sulfasalazine, also called slow-acting drugs. DMARDs work to slow inflammation and can, in many cases, alter the course of the disease. Until recently, most doctors reserved the use of DMARDs for patients who failed to respond to other therapies. Now, most physicians use DMARDs early and aggresively in the hope of slowing disease progression and damage to joints and internal organs.

The most recently approved treatment regimen for rheumatoid arthritis is one that combines the genetically engineered biological drug Remicade (infliximab) with the drug methotrexate. (Not all patients with rheumatoid arthritis can tolerate or respond to methotrexate alone, a standard treatment for the disease.) Remicade is the second in a new class of drugs known as biologic response modifiers, which bind to and block the action of a naturally occurring protein called tumor necrosis factor (TNF), believed to play a role in joint inflammation and damage. Elevated levels of TNF are found in the synovial fluid of rheumatoid arthritis patients.

Remicade, which is administered intravenously by a health-care professional in a two-hour outpatient procedure, was approved by the FDA in 1999 to reduce the signs and symptoms in patients who have not experienced significant relief from methotrexate alone.

Approved in 1996, Enbrel (etanercept) is the first biologic response modifier to receive FDA approval for patients with moderate to severe rheumatoid arthritis. Taken twice weekly by injection, Enbrel was shown to decrease pain and morning stiffness and improve joint swelling and tenderness. In 2000, the drug's uses were expanded to include delaying structural damage.

Jeffrey N. Siegel, M.D., a medical officer with FDA's Center for Biologics Evaluation and Research, says that Enbrel is an exciting breakthrough because it helps a majority of patients who have not responded to any of the other commonly used therapies. Although it is injected, the treatment can be administered at home. In addition, Enbrel has been shown to be effective for children with the juvenile form of rheumatoid arthritis. In clinical trials, Enbrel was generally well tolerated, and one of the most common side effects was an injection site reaction.

Both Remicade and Enbrel show promise in treating rheumatoid arthritis, although the long-term risks and benefits of these agents are unknown. In post-marketing reports, serious infections, including fatalities, have been reported with these agents. Caution should be used in patients with a history of recurring infections or with underling conditions that may predispose patients to infections.

Arava (leflunomide) is the first oral treatment approved for slowing the progression of rheumatoid arthritis. Although its effects are similar to those of methotrexate, this drug works by a different chemical mechanism that blocks at least one enzyme in certain immune cells called lymphocytes (a type of white blood cell that is part of the immune system), and thereby retards the progression of the disease.

However, Arava is not a cure for rheumatoid arthritis. It may cause birth defects, and the label carries a special warning for pregnant women and those planning to become pregnant. Liver damage, including deaths, also have been reported. The drug is not recommended for patients with severe immunodeficiency, bone marrow dysplasia, or severe, uncontrolled infections.

The first non-drug alternative for adult patients with moderate to severe rheumatoid arthritis and longstanding disease was approved by the FDA in 1999. The Prosorba column, which was initially approved in 1987 to treat an immune blood disorder, is a single-use medical device, about the size of a coffee mug, containing a material that binds antibodies and antigen-antibody complexes.

In a two-hour process performed in a hospital or specialized treatment center, a patient's blood is removed and passed through a machine that separates the blood cells from the plasma (the liquid portion of the blood). The plasma is then passed through the Prosorba column, recombined with the blood cells, and returned to the patient. Although this filtering process is believed to remove proteins that may inadvertently attack the joint cells, the mechanism of action of the Prosorba column is not well understood. The treatment is given once a week for 12 weeks. The most common side effects include joint pain and/or swelling, fatigue, hypotension (low blood pressure), and anemia.

"For those patients who have failed or are intolerant to DMARDs, including Arava and the anti-TNF agents," says Sahar M. Dawisha, M.D., a medical officer in the FDA's Center for Devices and Radiological Health, "the Prosorba column may be an additional treatment option."

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