Arthritis and Rheumatic Conditions, Biologic Treatments

by Food and Drug Administration (FDA)

(Page 3 of 5)

Managing Arthritis and Rheumatic Conditions

For years, the pain and inflammation of arthritis have been treated using medications, local steroid injections, and joint replacement — all with varying success. Seldom did the therapies make the pain go away completely or for very long, nor did they affect the underlying joint damage.

Today's researchers are working to improve diagnostic tools and develop treatments to forestall joint erosion. Even people whose joints are already damaged by arthritis can benefit from the knowledge generated by today's research. Patients should consult with their doctors to determine which treatments are the most appropriate for their conditions.

Most arthritis medications fall into three categories: those that relieve pain; those that reduce inflammation or the body process that causes swelling, warmth, and redness; and those that slow the disease process and limit further damage to the joints — so-called disease-modifying agents.

Pain relievers such as Tylenol (acetaminophen) and NSAIDs such as Motrin (ibuprofen) are used to reduce the pain caused by many rheumatic conditions. NSAIDs have the added benefit of decreasing the inflammation associated with arthritis. But a common side effect of NSAIDs is stomach irritation, which can often be reduced by changing the dosage or medication. Even acetaminophen has risks when taken in large doses, Kweder says.

Before safety concerns about Vioxx, Celebrex, and Bextra emerged in December 2004, these newer COX-2 NSAIDs were used primarily to reduce gastrointestinal side effects and offered an additional option for treatment.

Depending on the type of arthritis, a person may use a disease-modifying anti-rheumatic drug (DMARD). This category includes several unrelated medications that are intended to slow or stop disease progress and prevent disability and discomfort. DMARDs include Rheumatrex (methotrexate), Azulfidine (sulfasalazine), and Arava (leflunomide).

Someone diagnosed with RA today is likely to be prescribed a DMARD fairly early in the course of the disease, as doctors have found that starting these drugs early can help prevent irreparable joint damage that might otherwise occur.

Corticosteroids, such as prednisone, cortisone, methylprednisolone, and hydrocortisone, are used to treat many rheumatic conditions because they decrease inflammation and suppress the immune system. The dosage of these medications will vary depending on the diagnosis and the patient. Corticosteroids can be given by mouth or by direct injection into a joint or tendon sheath.

For Shirley, any minor relief he experienced over the 25 years was due to injections of corticosteroid preparations into his joints. The injections would relieve his pain, stiffness, and swelling temporarily. Unfortunately, corticosteroids given orally and for prolonged periods and at higher doses may carry side effects such as brittle bones, cataracts, elevated blood sugar, and an increased susceptibility to infections throughout the body.

Biologic Treatments

Biological products are a relatively new class of drugs used for the treatment of RA. Biologics differ from conventional drugs in that they are derived from living sources, such as cell culture systems. Conventional drugs are chemically synthesized. Of the four currently licensed biologics, three help reduce inflammation and structural damage of the joints by blocking a substance called tumor necrosis factor (TNF), a protein involved in immune system responses. Elevated levels of TNF are found in the synovial fluid of rheumatoid and some other arthritis patients.

The first biologic to receive FDA approval for patients with moderate-to-severe RA was Enbrel (etanercept). Initially, it was taken twice weekly by injection, but a once-weekly preparation is now available. Enbrel has been shown to decrease pain and morning stiffness and improve joint swelling and tenderness. In 2000, the drug's approved uses were expanded to include delaying structural damage. Besides RA, Enbrel now has been approved for two other common forms of arthritis: psoriatic arthritis and ankylosing spondylitis.

The two other TNF-blocking products approved to treat RA are Remicade (infliximab) and Humira (adalimumab), a drug that provided the long-awaited relief for Shirley through a 2002 clinical trial. All three TNF blockers have been demonstrated to improve physical function in studies of at least two years in duration.

"While all three inhibit the action of TNF," says Jeffrey N. Siegel, M.D., team leader for the FDA's Division of Therapeutic Biological Internal Medicine Products, "they do it in somewhat different ways." Remicade and Humira are monoclonal antibodies, laboratory-produced proteins similar to those made by a person's immune system that bind and remove TNF from the body before it can set off the immune reaction responsible for RA.

Enbrel, on the other hand, is a soluble cytokine receptor, which means it is similar in structure to protein molecules found attached to the surface of cells that bind TNF. Enbrel competes with these receptors to inhibit them from binding TNF, thus blocking them from setting off the immune process responsible for RA, psoriatic arthritis, and ankylosing spondylitis.

Siegel warns that caution is important when using these agents as treatments. "All TNF blockers are associated with infection," he says.

Kineret (anakinra), another biologic approved by the FDA for patients with RA, has been shown in clinical trials to improve pain and swelling and slow the progression of structural damage in patients.

About the Author

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