WEDNESDAY, Nov. 12, 2003 (HealthDayNews) -- An experimental drug that blindfolds immune system cells that attack the body is better than conventional care for rheumatoid arthritis, new research finds.
The drug, a protein that goes by the alphabetical mouthful CTLA4Ig, prevents T-cells from "seeing" and going after their targets in joint tissue. People who took CTLA4Ig in addition to the conventional therapy for rheumatoid arthritis (RA) were nearly twice as likely to show a 20 percent reduction in joint pain and swelling, among other symptoms, as those on the usual treatment alone.
Those on the drug -- which prevents T-cells from binding with one of two molecules that activate them -- were also more likely to experience more dramatic improvement, though the number of patients who did so was small.
Dr. Anne Davidson, an arthritis expert at Albert Einstein College of Medicine in the Bronx, calls the effect of the new drug "pretty good" and says it comes close to that of RA drugs that have recently come to market. These drugs, which include Enbrel, block an inflammatory signaling molecule called tumor necrosis factor, or TNF.
While the principal effect of CTLA4Ig is to keep T-cells inactive, Davidson says the drug also squelches inflammation in other ways, such as by preventing immune cells from migrating to sites of inflammation.
The drug is being developed by Bristol-Myers Squibb Co., which funded the latest research. It has not yet been approved for sale in the United States or abroad. Results of the new study appear in the Nov. 13 issue of the New England Journal of Medicine.
Study coauthor Dr. Larry Moreland, a joint specialist at the University of Alabama, Birmingham, says CTLA4Ig will have to go head-to-head against other RA therapies before its real value is clear. "In a placebo-controlled trial this was much better than placebo and it appears to be an effective agent," he says. Additional research on the drug is now under way.
Rheumatoid arthritis is a potentially debilitating disease in which the immune system turns on cartilage in the joints and tissue in other organs. The condition, which causes pain, fatigue, swelling and other symptoms, affects an estimated 2.1 million Americans, most of whom are women, according to the Arthritis Foundation. What triggers RA is unknown.
RA often responds well to drug therapy, most commonly steroids such as prednisone and the immune-suppressing drug methotrexate, also prescribed for certain cancers. Patients frequently use painkillers and nonsteroidal anti-inflammatory drugs (NSAIDs) in combination with the stronger medications.
While these regimens can be extremely effective, they don't work in many patients and may lead to serious side effects, including infections and cancers. Many times, patients stop responding to the standard drugs after a promising start. In most cases, full remission of symptoms never occurs, Moreland says.
In the latest study, an international team of researchers gave CTLA4Ig or sugar pills to 339 men and women with RA. Some of the patients, all of whom were taking methotrexate, received a low dose of 2 milligrams a day per kilogram of body weight, while others took a much higher dose of 10 milligrams/kilogram.
After six months, patients on the highest dose showed significantly more improvement in arthritis symptoms than those on methotrexate alone. Between 16 percent and 17 percent of patients on the highest dose had a 70 percent improvement in symptoms, compared with about 11 percent of those on the small dose and just 1.7 percent of those on methotrexate only. Moreland says that's a rough estimate of how many patients might expect to experience full remission of symptoms, although that figure must be established in future studies.
People who took CTLA4Ig had markedly lower blood levels of a molecule called C-reactive protein than those who didn't receive the drug, suggesting a significant suppression of inflammation. "We really need and expect to see a decrease in inflammation," says Moreland, who has been a paid consultant for Bristol-Myers Squibb.
Patients on CTLA4Ig reported improvements in a variety of daily activities, from physical function and general health to social and emotional well-being. The drug didn't seem to cause any serious side effects.
The new medication, and other novel treatments now being tested, "may enable patients who fail one class of drugs to utilize another," Dr. David Karp, a medical advisor to the Arthritis Foundation, says in a statement.
"It may also be possible to use combinations of drugs to achieve greater effect with fewer side effects. The biggest challenge," Karp adds, "will be to determine if there is a preferential order to use these drugs or certain beneficial combinations."
More information
Try the Arthritis Foundation or the National Institutes of Health.
