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Arthritis: Timely Treatments for an Ageless Disease

MYTH: Arthritis affects only older people.

FACT: Arthritis affects any age, including children. There's no question that the incidence of arthritis increases with age, but nearly three of every five sufferers are under age 65.

MYTH: Arthritis is just minor aches and pains.

FACT: Arthritis can be permanently debilitating.

MYTH: Arthritis cannot be treated.

FACT: The FDA recently approved several new treatments for osteoarthritis and rheumatoid arthritis.

The fact is, these myths keep people from seeking a doctor's help against the number one cause of disability in the United States, according to the national Centers for Disease Control and Prevention. Arthritis disables more Americans than heart disease and stroke, and the CDC says it's what Americans don't know about the disease that can hurt them.

"People ignore arthritis both as public and personal health problems because it doesn't kill you," says Chad Helmick, a medical epidemiologist at the CDC. "But what they don't realize is that as Americans work and live longer, arthritis can affect their quality of life and eventually lead to disability." Current costs to the U.S. economy total nearly $65 billion annually-an impact equal to a moderate recession.

And the extent of the suffering is going to get worse. Arthritis already affects more than 42 million Americans in its chronic form, including 300,000 children. By 2020, CDC estimates that 60 million people will be affected, and that more than 12 million will be disabled.

The Arthritis Foundation and the American College of Rheumatology agree that awareness, early diagnosis, and an aggressive treatment plan developed by a doctor are key to stopping arthritis from taking over your life.
What Is Arthritis?

Although the term literally means joint inflammation, arthritis really refers to a group of more than 100 rheumatic diseases and conditions that can cause pain, stiffness and swelling in the joints. Certain conditions may affect other parts of the body-such as the muscles, bones, and some internal organs-and can result in debilitating, and sometimes life-threatening, complications. If left undiagnosed and untreated, arthritis can cause irreversible damage to the joints.

The two most common forms of the disease, osteoarthritis and rheumatoid arthritis, have the greatest public health implications, according to the Arthritis Foundation. (For more on other causes of joint pain, see "Other Forms of Arthritis and Related Conditions.")

Osteoarthritis, previously known as "degenerative joint disease," results from the wear and tear of life. The pressure of gravity-the load of living-causes physical damage to the joints and surrounding tissues, leading to pain, tenderness, swelling, and decreased function. Initially, osteoarthritis is noninflammatory and its onset is subtle and gradual, usually involving one or only a few joints. The joints most often affected are the knee, hip and hand. Pain is the earliest symptom, usually made worse by repetitive use. Osteoarthritis affects 21 million people, and the risk of getting it increases with age. Other risk factors include joint trauma, obesity, and repetitive joint use.

Rheumatoid arthritis is an autoimmune disease that occurs when the body's own immune system mistakenly attacks the synovium (cell lining inside the joint). This chronic, potentially disabling disease causes pain, stiffness, swelling, and loss of function in the joints.

To see an illustration of the cross section of a normal knee joint and the effects of osteoarthritis and rheumatoid arthritis, select the
graphic at right.

While the cause remains elusive, doctors suspect that genetic factors are important in rheumatoid arthritis. Recent studies have begun to tease out the genetic characteristics that can be passed from generation to generation. However, the inherited trait alone does not cause the illness. Researchers think this trait, along with some other unknown factor-probably in the environment-triggers the disease.

But rheumatoid arthritis can be difficult to diagnose early because it may begin gradually with subtle symptoms. According to the CDC, this form of arthritis affects more than 2 million people in the United States, and two to three times more women are affected than men.
Finding Effective Treatments

For years, the pain and inflammation of arthritis have been treated with varying success, using medications, local steroid injections, and joint replacement. Seldom did the therapies make the pain go away completely or for very long, nor did they affect the underlying joint damage. Just ask Jo Ellen Gluscevich, who has tried more drugs and treatments than she can remember, to no avail.

"It seems I've tried them all," says the 50-year-old from Frederick, Md., who was diagnosed with rheumatoid arthritis 10 years ago. "Every year continues to be a challenge for me medically."

But now there are some new treatments available, and patients should consult with their doctors to determine which are the most appropriate for their conditions.
Osteoarthritis

When taken regularly and at high doses, traditional nonsteroidal anti-inflammatory drugs (NSAIDs) used for pain relief can cause gastrointestinal (GI) bleeding or ulcers. But a new type of NSAID, cyclooxygenase-2 inhibitors, better known as COX-2 inhibitors, has joined the old standbys. These drugs help suppress arthritis with less stomach irritation.

Cyclooxygenases are enzymes needed for the synthesis of hormone-like substances called prostaglandins. There are two types of cyclooxygenases: the COX-2 enzyme that mediates inflammation and pain, and the COX-1 enzyme that helps maintain other physiological functions in the body. Traditional NSAIDs inhibit both enzymes. The new NSAIDs, however, block mostly the COX-2 enzyme, offering a new treatment option for people who have had difficulty tolerating the old NSAIDs.

"COX-2 inhibitors are just as effective in treating osteoarthritis as other NSAIDs," says Maria Villalba, M.D., a medical officer with the Food and Drug Administration's Center for Drug Evaluation and Research.

The FDA approved the first COX-2 inhibitor, Celebrex (celecoxib), in 1998 to treat rheumatoid arthritis and osteoarthritis. Vioxx (refecoxib) became the second COX-2 inhibitor to receive approval, in 1999, for the treatment of osteoarthritis, dysmenorrhea (pain with menstrual periods), and the relief of acute pain in adults, such as that caused by dental surgery.

Both drugs, taken orally, were found to substantially lower the risk of stomach and upper intestinal ulcers detected by endoscopy in clinical trials, compared with some of the other NSAIDs tested. However, two recently completed large clinical studies of approximately one-year duraton did not support removal of the standard NSAID warning of the risk of serious gastrointestinal events from the Celebrex and Vioxx labels. These large studies did not show an advantage in overall safety (as measured by the total number of deaths, serious adverse events, discontinuations and hospitalizations due to adverse events) favoring the selective COX-2 inhibitors campared to the other NSAIDs tested.

Two non-drug alternatives for the treatment of pain in osteoarthritis of the knee were approved by the FDA's Center for Devices and Radiological Health in 1997 for patients who have failed to respond adequately to simple analgesics, such as acetaminophen, and to conservative nonpharmacologic therapy. Hyalgan and Synvisc are viscous solutions composed of hyaluronan (hyaluronic acid, a lubricant found naturally in the joints), and are injected directly into the knee joint. Both are believed to increase the quality of synovial fluid, although the mechanism of action for these products is not well understood. The most common side effects reported from these treatments-injection site pain and knee pain and/or swelling-were found to be temporary. For patients who cannot tolerate oral medications and who are not candidates for surgical knee replacement, these treatments may be an ideal option.
Rheumatoid Arthritis

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."
Exercise and Arthritis

Proper exercises performed on a regular basis are an important part of arthritis treatment, according to the Arthritis Foundation. Twenty years ago, doctors advised exactly the opposite, fearing that activity would cause more damage and inflammation. Not exercising causes weak muscles, stiff joints, reduced mobility, and lost vitality, say rheumatologists, who now routinely advise a balance of physical activity and rest.

According to the 1996 Surgeon General's Report on Physical Activity and Health, regular, moderate physical activity is beneficial in decreasing fatigue, strengthening muscles and bones, increasing flexibility and stamina, and improving the general sense of well-being. The National Institutes of Health (NIH) advises that the amount and form of exercise should depend on which joints are involved, the amount of inflammation, how stable the joints are, and whether a joint replacement procedure has been done. A skilled physician who is knowledgeable about the medical and rehabilitation needs of people with arthritis, working with a physical therapist, can design an exercise plan for each patient.