Treatments for Rheumatoid Arthritis: NSAIDs and Cox-2 Inhibitors

For many years, nonsteroidal inflammatory drugs (NSAIDs) have been the first choice of doctors to control the joint swelling and inflammation associated with rheumatoid arthritis (RA). Almost everyone with the condition has taken or is taking one of these drugs.

Although the medicines cannot cure the disease, NSAIDs have been successful at alleviating the inflammation associated with rheumatoid arthritis. The drugs appear to help pain, morning stiffness and range of motion in the joints. Also, they have been able to reduce the limitations on daily activities often caused by rheumatoid arthritis.

NSAIDs are available in a wide variety of strengths and formats. Less powerful strengths can be purchased over the counter, while more potent versions are sold only by prescription. They are available as oral tablets, capsules or liquids. Typical NSAIDs include ibuprofen (Advil®, Motrin®), naproxen (Anaprox®, Naprosyn®), tolmetin (Tolectin®), diclofenac (Voltaren®), nabumetone (Relafen®), indomethacin (Indocin®), ketoprofen (Orudis®, Oruvail®) and even aspirin. Your doctor can help you decide which NSAID is right for you and your condition.

How NSAIDs Work
NSAIDs work by preventing the body from producing prostaglandins. Prostaglandins are hormone-like substances that have been identified as a cause of pain, inflammation and fever in the body. They are produced within the body's cells by cyclo-oxygenase (Cox) enzymes called Cox-1 and Cox-2.

Prostaglandins are important, because they are involved in the function of the platelets that cause blood to clot. They also aid in the production of the natural mucus lining that protects the stomach lining from the damaging effects of acid. Cox-1 and Cox-2 enzymes produce prostaglandins that promote inflammation, pain and fever. However, only the Cox-1 enzyme produces prostaglandins that support blood clotting platelets and protect the stomach.

Since NSAIDs block both Cox enzymes, they do more than just reduce the responses of inflammation, pain and fever. By also inhibiting the Cox-1 enzyme, there is evidence that NSAIDs may cause problems in the stomach, since it is the Cox-1 enzyme that protects the stomach lining.

NSAID Side Effects
Research shows that about 15 percent of patients on long-term NSAID treatment develop stomach ulcers. Many of these patients have no symptoms and are unaware of their ulcers. However, they are at risk for developing serious and potentially life-threatening ulcer complications, such as bleeding or perforations of the stomach.

However, gastric problems aren't the only side effects associated with NSAIDs. Some side effects are mild and go away on their own or go away after a reduction in dosage. Others are more serious and may require medical attention. They include an increased tendency to bleed, headaches and dizziness, a ringing in the ears, allergic reactions such as rashes, wheezing and throat swelling and liver or kidney problems. Additional problems that may arise include high blood pressure and swelling in the legs.

When NSAIDs are needed for prolonged periods, these side effects can be controlled with blood tests and regular monitoring by a physician. Gastric problems can be averted or at least kept to a minimum, by taking the drugs in low doses for brief periods. When NSAIDs are needed for longer periods of time, a variety of medicines may be recommended to prevent the gastric side effects. Antacids, for example, prevent the production of excess stomach acid. Drugs like sucralfate (Carafate®) help coat and protect the stomach. Medications like misoprostol (Cytotec®) help restore the lost mucus.

A New Class of NSAIDs: Cox-2 Inhibitors
A newer class of NSAIDs known as Cox-2 inhibitors (COXIBs) suppresses only Cox-2, the enzyme that is involved in the inflammation but not in the protection of the stomach. Because of this, Cox-2 inhibitors, such as celecoxib (Celebrex®), allegedly reduce the risk of the gastrointestinal complications associated with traditional NSAID therapy. Cox-2 inhibitors are more expensive than older NSAIDs, but they are not considered more effective at reducing the pain and inflammation of rheumatoid arthritis.

They also carry their own set of risks. In fact, in 2005, the makers of two Cox-2 inhibitors, rofecoxib (Vioxx®) and valdecoxib (Bextra®), voluntarily pulled the drugs from the market because of reports that they may increase the risk of heart attack, heart failure and stroke, especially in people who are known to already have heart disease. Studies have found that these drugs may also cause fluid retention and high blood pressure or that they may exacerbate an existing high blood pressure condition.

Now, Celebrex, the only Cox-2 inhibitor still available, carries a prominent "black box warning" on its packaging—the U.S. Food and Drug Administration's strongest warning—that it may be linked to an increased risk of cardiovascular events.

In 2005, the FDA also announced new label requirements for prescription and nonprescription NSAIDs. Now, their packaging includes the same black box warning as the Cox-2 inhibitors. The warning highlights the increased risk of heart attack and stroke, as well as the potential for gastrointestinal bleeding. Manufacturers of Celebrex and all other prescription NSAIDs have since revised their labeling to include a medication guide for patients to ensure they use these drugs properly.

Take Precautions With NSAIDs
To ensure that NSAIDs are taken safely, patients should use them with a doctor's supervision. They carry certain risks and may cause or worsen medical problems if taken at the same time as other medications or if certain health conditions are present. For example, individuals who are taking anticoagulants, such as warfarin sodium (Coumadin®), should be monitored for the potential of increased bleeding. A doctor's supervision is also necessary because NSAIDs may cause fluid retention, which can decrease the effectiveness of high blood pressure medication and diuretics.

Many patients with rheumatoid arthritis take methotrexate, and its toxicity may increase when NSAIDs are used. Because corticosteroids and high doses of aspirin may increase the risk of developing peptic ulcers or gastrointestinal bleeding, a condition which can be aggravated by NSAID use, caution is advised. Some NSAIDs can also interfere with aspirin, which is sometimes taken to prevent heart disease.

People with certain health conditions should not take NSAIDs. Those conditions include an allergy to NSAIDs, peptic ulcer disease, bleeding disorders and kidney function impairment. Pregnant women are also told to avoid using NSAIDs during the last three months of their pregnancy.

Finally, patients should call their health professional if they experience severe stomach pain, bloody vomit, bloody or black tar-like stools, bloody or cloudy urine, unexplained bruising or bleeding, wheezing or breathing troubles, swelling in the face or around the eyes, severe rash or red, itchy skin. These conditions require immediate medical consultation.

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