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Medical Editor:

Melissa Conrad Stöppler, MD, Chief Medical Editor

Melissa Conrad Stöppler, MD, Chief Medical Editor

Melissa Conrad Stöppler, MD, is a U.S. board-certified Anatomic Pathologist with subspecialty training in the fields of Experimental and Molecular Pathology. Dr. Stöppler's educational background includes a BA with Highest Distinction from the University of Virginia and an MD from the University of North Carolina. She completed residency training in Anatomic Pathology at Georgetown University followed by subspecialty fellowship training in molecular diagnostics and experimental pathology.

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Nonsteroidal anti-inflammatory drugs (NSAIDs): These drugs reduce swelling and pain but do not stop joint damage and alone are not sufficient to treat rheumatoid arthritis. These drugs work by blocking an enzyme called cyclo-oxygenase (COX) that promotes inflammation. There are at least two forms of the enzyme: COX-1 and COX-2. Some people with a history of stomach ulcers or liver problems should not take these drugs. This group includes aspirin, although aspirin is rarely used in rheumatoid arthritis because it is not as safe as other agents.

• COX-2 inhibitors: These agents block only the COX-2 enzyme and are often referred to as selective NSAIDs. They have fewer side effects than the other NSAIDs while still reducing inflammation. Only celecoxib (Celebrex) currently remains on the U.S. market.
• On Sept. 30, 2004, Merck & Co, Inc., announced a voluntary withdrawal of the COX-2 inhibitor rofecoxib (Vioxx) from the U.S. and worldwide market because of its association with an increased rate of cardiovascular events (including heart attacks and strokes) compared to that of placebo. A major U.S. Food and Drug Administration (FDA) study of rofecoxib found an apparent threefold increase in the risk of sudden cardiac death or heart attack among patients who had taken higher doses of the drug compared to the risk of patients who had not recently received similar medication. The report showed that even patients taking the standard starting dose of 12.5 mg or 25 mg of rofecoxib had a 50% greater chance of heart attack or sudden cardiac death than patients on any dose of celecoxib (Celebrex). The large-scale study was conducted after analyzing the medical records of 1.4 million people insured by Kaiser Permanente in Oakland, Calif., between 1999-2001. Note: The study had inherent limitations in that it was observational, rather than randomized and controlled.
• On Apr. 7, 2005, valdecoxib (Bextra, by Pfizer, Inc.) was voluntarily withdrawn from the U.S. market, pending further discussion with the FDA. The association of valdecoxib with potentially life-threatening risks, including myocardial infarction, stroke, and serious skin reactions, initiated an investigation to determine whether the benefits of the drug outweighed the risks. The serious skin reactions are most likely to occur in the first two weeks of treatment, but they can occur any time during therapy. Other COX-2 inhibitors and traditional NSAIDs (for example, naproxen [Aleve, Naprosyn], ibuprofen [Motrin]) also have a risk for these rare, serious skin reactions, but the reported rate of the reaction appears to be greater for valdecoxib. Newer data regarding risks in individuals who take valdecoxib following heart bypass surgery showed an increased risk of heart attack, stroke, deep vein thrombosis (blood clots in the leg), and pulmonary embolism (blood clots in the lungs).
• Nonselective NSAIDs: These drugs block both COX-1 and COX-2. They include ibuprofen (Motrin, Advil, etc.), ketoprofen (Oruvail), naproxen (Naprosyn), piroxicam (Feldene), and diclofenac (Voltaren, Cataflam).

Analgesics: These agents reduce pain but do not affect swelling or joint destruction.

• Acetaminophen (Tylenol, Feverall, Tempra): This drug is often used by people who cannot take NSAIDs because of hypersensitivity, ulcers, liver problems, or interactions with other drugs.
• Tramadol (Ultram)
• Opioids: These drugs may be used to treat moderately severe to severe pain that is not relieved by other analgesics.

For more information on these medications, see Understanding Rheumatoid Arthritis Medications.

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