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Spinal Disorder Therapy Identified

Study: German team says infliximab, an immune blocker, is first effective treatment for anklyosing spondylitis.


German researchers have identified the first effective therapy for anklyosing spondylitis, a degenerative spinal disorder that affects more than 300,000 Americans.

The team found that the immune blocker infliximab--already used for treating rheumatoid arthritis and Crohn's disease--sharply reduced disease symptoms in 53% of patients with the disorder and produced at least some improvement in 80%.

The only current treatments for AS, as it is known, are aspirin and similar drugs and physical therapy, said Dr. Jurgen Braun of the German Rheumatism Research Centre in Berlin. "We would just watch the patient getting stiffer all the time. Now there seems to be something really working strongly."

AS varies in severity from intermittent episodes of back pain to a severe chronic disease that attacks the spine, peripheral joints and other organs, resulting in severe stiffness, loss of motion and deformity.

The discovery, reported in this week's issue of Lancet, "is important because people don't often do studies with this disease," said Dr. Jack Klippel, medical director of the Arthritis Foundation. "This is a major form of arthritis for which there are no officially approved therapies."

In a separate study in the same journal, a team from the University of Kansas School of Medicine reported that the arthritis drug methotrexate can prevent premature death in patients with rheumatoid arthritis, which afflicts about 1% of the population.

"Now we can begin to think of drug therapy in several realms," Klippel said. "It improves the signs and symptoms of arthritis, it prevents damage to joints and limits disability, and now for the first time we have evidence that it can prolong life."

Both anklyosing spondylitis and rheumatoid arthritis are autoimmune diseases in which, for reasons that are not fully explained, the immune system attacks a person's body. In AS, the disease attacks primarily the spine and the sacroiliac. In rheumatoid arthritis, it attacks joints throughout the body. Both disorders can cause damage to other organs as well, especially the heart, and people with rheumatoid arthritis tend to die about 10 years earlier than their healthy peers.

Rheumatoid arthritis is more likely to affect females than males, by a ratio of about 3 to 1, while AS strikes males in about the same ratio. Rheumatoid arthritis strikes in middle age, while AS hits men at around age 26.

In the last few years, researchers have identified a common thread in several arthritic diseases: the role of an immune system chemical called tumor necrosis factor, or TNF-alpha. Overproduction of TNF-alpha leads to inflammation, producing many of the symptoms of the disorders.

Infliximab, trade-named Remicade, is designed to bind to TNF-alpha in the bloodstream and remove it from circulation. A combination of infliximab and methotrexate, which also suppresses inflammation, is now the most common treatment for advanced rheumatoid arthritis. A similar drug called etanercept, trade-named Enbrel, works in the same way.

Braun and his colleagues studied 34 AS patients who received infliximab and 35 who received a placebo. Improvement in patients receiving the drug became apparent in as little as two weeks and was obvious after a month, even though they didn't know which patients were receiving the drug, Braun said.

At the end of three months, 18 of the patients receiving infliximab had at least a 50% reduction in symptoms, compared with only three of those receiving the placebo.

About 30% of the patients also suffered from peripheral arthritis, a complication of AS, he said. Among those receiving the drug, "that went away very quickly."

Braun conceded that "we still don't know how this will work in the long term. But in the short term, we now have data for some patients for one year, and we think this is a very good therapy."

In the rheumatoid arthritis study, Dr. Frederick Wolfe and his Kansas colleagues studied 1,240 people who were seen at an arthritis clinic between January 1981 and December 1999. Of those, 588 of the sickest received treatment with methotrexate. (Infliximab was not approved until 1998.)

Over the follow-up period, 72 of the patients receiving methotrexate died, as did 119 of those not receiving the drug. Taking into account that those receiving methotrexate were sicker to begin with, Wolfe concluded that those receiving the drug were 60% less likely to die prematurely than those not receiving it. They were 70% less likely to die of heart disease.

Experts said that the findings were suggestive but not conclusive because other factors might have played a role in the drug group's survival. A more definitive study would randomly assign patients to receive either the drug or a placebo, and that was not done in this case.

Nonetheless, Klippel said, there has not been any previous study that asked whether treatment can prolong survival. "Now the answer is clearly yes."

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