A new drug for arthritis

Thousands of people who have been taking the arthritis drug rofecoxib (Vioxx) are now switching to other medications. Vioxx was pulled from pharmacy shelves in September after a colon polyp prevention trial was stopped due to an increased risk of heart attack and stroke among patients randomized to take the drug. The risks emerged after 18 months during that particular trial. And although the US special Food and Drug Administration advisory panel recently said that Vioxx-maker Merck may bring the controversial drug back to pharmacies as long as they have warning labels, some analysts feel that this move may be unlikely.

With choices narrowing, the dilemma now facing people with osteoarthritis (OA) is whether to take traditional nonsteroidal antiinflammatory drugs (NSAIDs), such as ibuprofen (Motrin, Advil) or diclofenac (Voltaren, Cataflam), or other prescription drugs in the same class as Vioxx, celecoxib (Celebrex), valdecoxib (Bextra), and etoricoxib (Arcoxia). None are risk-free. The best choice is determined by your particular medical history and whether the benefits outweigh potential cardiac and gastrointestinal side effects.

Heart Of The Matter

Vioxx, Celebrex, Bextra, and Arcoxia belong to a class of medications called cyclooxygenase –2 (COX-2) inhibitors. The COX-1 enzyme protects the lining of the stomach from acid and is needed for blood clotting; the COX-2 enzyme promotes pain and inflammation, but also helps inhibit clot formation and causes vasodilatation. Aspirin and older NSAIDs affect both COX enzymes, reducing pain and inflammation but also increasing the risk of stomach ulcers and bleeding. COX-2 inhibitors were developed to pose less risk of stomach problems than aspirin, ibuprofen, and naproxen (Naprosyn).

Since COX-2 helps inhibit blood clot formation, blocking its effects could be what increased the risk of heart attack and stroke in the studies of Vioxx, says Sudhir Diwan, MD, director of the Division of Pain Medicine at Weill Cornell Medical Center in New York. "These drugs can also cause fluid retention and raise blood pressure to a certain extent. So several factors may be contributing to the increased cardiovascular risk."

While there was evidence of such risks from observational studies of Vioxx, most studies compared it to other NSAIDs such as naproxen, which may be cardioprotective, notes Mark Fendrick, MD, professor of Internal Medicine at the University of Michigan, who has studied NSAID safety. "The polyp prevention trial (APPROVe) was the first to compare Vioxx to a placebo, and provided definitive evidence that it caused a higher rate of cardiovascular events."

As for Bextra, a clinical study of more than 1,500 bypass patients found an increased risk of heart attack and stroke among those who took the drug orally or intravenously. Thus, in mid-October, Bextra’s manufacturer warned that its drug increased heart attack risk in patients who had coronary artery bypass operations. So far, the same heart risks have not been seen in short-term studies of Celebrex. But the US Food and Drug Administration (FDA) is convening an expert panel soon to discuss the overall safety of COX-2 drugs. One NSAID, meloxicam (Mobic), has a different mechanism of action.

What’s Right For You?

If you are over 65, have a history of ulcers, gastric bleeding, or take blood thinners like Coumadin, literally go with your gut and avoid older NSAIDs (or add a gastroprotective agent) or opt for non-NSAID therapy, advises Dr. Fendrick.

Of the medications to protect your stomach, the best choices are called proton pump inhibitors (PPIs), including omeprazole (Losec), esomeprazole (Nexium), pantoprazole (Ulcepraz, Pantoloc), and rabeprazole (Pariet).

No NSAID is totally risk-free. New safety labeling for ibuprofen warns that higher-than-recommended doses may also cause gastric bleeding. People with heart risks may also consider acetaminophen (Tylenol), which doesn’t irritate the stomach or fight inflammation. But French researchers reported in the September 2004 issue of the Annals of Rheumatic Diseases that 400 mg of ibuprofen was more effective than a 1,000 mg dose of acetaminophen in relieving the pain and stiffness of knee or hip OA. Still, for minor OA pain, some people find acetaminophen effective, says Dr. Fendrick. Taking too much Tylenol can cause liver problems. Talk with your doctor before using ibuprofen if you have high blood pressure, heart, or kidney disease. "With any medication, use the lowest possible dose that relieves your pain," he stresses.

Aspirin For The Heart

A recent study has found that many people who take COX-2 drugs also take aspirin to prevent heart attacks, which could increase the risk of ulcers. "Most patients and many clinicians are not aware that adding aspirin to a COX-2 takes away most, if not all, the gastrointestinal safety benefit," comments Dr. Fendrick.

If you have risk factors for heart attack or stroke, consider taking low-dose (81 mg) aspirin, naproxen, and a PPI. If you have no cardiovascular risk factors, take an NSAID other than aspirin, he adds.

If you use both low-dose aspirin and ibuprofen, take aspirin at least two hours beforehand; a 2001 study found that when the two drugs were taken at the same time, ibuprofen interfered with aspirin’s anti-clotting properties.

Exercise Is Important

Most experts stress that exercise or physical therapy should be your first line of defense against joint pain. The American Academy of Physical Medicine and Rehabilitation calls exercise "joint self-repair," because careful movement helps keep joints well-lubricated, minimizing pain. Exercise also strengthens the muscles and tendons that support the joints. You can find special exercise programs for people with arthritis through the Arthritis Foundation (www.arthritis.org). Couple exercise with weight loss to help lessen the load on your joints.

Supplements

Non-drug remedies include supplements such as glucosamine and chondroitin (either alone or in combination). They have been shown to be helpful in relieving pain and improving joint function. Both nutrients are components of normal cartilage and help retain moisture in the joint; glucosamine is said to help rebuild cartilage. Glucosamine supplements are derived from the shells of shrimp, lobster, and crab, and should be avoided by anyone allergic to shellfish. Chrondroitin is made from bovine cartilage. The dose of glucosamine used in clinical trials is 1,500 mg a day. The generally accepted dose of chondroitin is 800-1,200 mg a day.

Avocado / soybean unsaponifiables (ASU), is a mixture of processed fats from soy and avocado. ASU may reduce inflammation and induce cartilage repair, according to short-term European clinical trials. It has not been clinically tested in other countries. ASU is available in the US as Avosoy.

The supplements S-adenosylmethionine (SAM-e) and methylsulfonylmethane (MSM) are also said to reduce joint pain in OA, but data is limited.

Creams And Ointments

Creams containing salicylates (Oil of Wintergreen) inhibit transmission of pain signals. Creams or ointments containing capsaicin (in the US, capsaicin-P, Zostrix), the active chemical in hot peppers, act as a counterirritant to "distract" pain receptors. Creams and patches that contain menthol or camphor to create the sensation of heat or coolness (BenGay, Icy Hot) also act as counterirritants.

Discuss the severity of your joint pain with your physician and, together, carefully weigh each therapy’s risks in relation to its benefits. Yes, there’s life after Vioxx if you have arthritis!