Anti-TNF drugs bring relief from rheumatoid arthritis

DEAR READER:

Rheumatoid arthritis (RA) is a chronic autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in the joints. Our immune systems are not supposed to attack our own tissues; they're supposed to attack foreign things that enter our body, particularly germs. In autoimmune diseases, however, something goes haywire.

When the immune system attacks anything -- a foreign germ or the body's own tissue -- it acts like an army. There are immune system cells that are like the generals: They direct the troops. They do so by sending chemical signals that tell other cells to attack or to stop attacking.

One of these chemical signals is a molecule called tumor necrosis factor, or TNF. It's one of the "attack" signals. TNF binds to normal joint tissues and increases inflammation. Anti-TNF drugs bind to the receptor sites on the joint tissue cells, blocking the TNF from causing destructive

inflammation. (There's an illustration of how anti-TNF drugs work on my website, AskDoctorK.com.) In rheumatoid arthritis, the inflammation begins in the synovium, a thin membrane that lines the joints. There, something (we don't yet know what) triggers an inflammatory reaction. As a result, joint cells produce harmful substances that attack the joints themselves. Synovial cells also proliferate, forming a rough, grainy tissue that grows into the joint cavity and eats away at cartilage.

These changes cause a number of uncomfortable symptoms:

-- Constant or recurring pain or tenderness in joints

-- Stiffness and difficulty using or moving joints normally

-- Swelling in and around joints

-- Warmth and redness in joints

-- Weight loss

-- Low-grade fever

-- Fatigue

-- Prolonged morning stiffness

The goals in treating RA are to prevent or control joint damage, prevent loss of function and reduce pain. Joint damage begins early in the course of the disease. To prevent permanent damage, the disease is often treated aggressively from the start.

Anti-TNF agents are among a newer generation of drugs. They can dramatically improve the symptoms of rheumatoid arthritis and slow the progressive damage to the joints that often occurs. Five anti-TNF agents are now available:

-- adalimumab (Humira)

-- certolizumab (Cimzia)

-- etanercept (Enbrel)

-- infliximab (Remicade)

-- golimumab (Simponi)

Anti-TNF drugs are potent and expensive, and they can have serious side effects. But they appear to do what other drugs have failed to do: stop the rate of joint deterioration. In fact, in a number of people with RA, these drugs have induced something close to remission.

For this reason, the discovery of anti-TNF drugs has been honored with some of medicine's biggest prizes. They are just another example of how government investment in basic medical research, followed by drug development by the private sector, can improve people's lives.

(Dr. Komaroff is a physician and professor at Harvard Medical School. To send questions, go to AskDoctorK.com, or write: Ask Doctor K, 10 Shattuck St., Second Floor, Boston, MA 02115.)

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