New approaches to treating autoimmune disease are producing some of the most promising results in patients with rheumatoid arthritis. Dr. Edward Keystone, director of the Centre for Advanced Therapeutics at Mount Sinai Hospital in Toronto, has played an important role in examining the use in Canada of a number of genetically engineered drugs that appear to work faster, show as much improvement (if not more) and appear to make patients less susceptible to infection than traditional immunosuppressive drugs, such as methotrexate and cortisone. “The patients have shown significant improvement in the early studies. There is less pain, less stiffness and less swelling. On average, patients improve within a few weeks and are substantially better within three months,” says Dr. Keystone.
Rheumatoid arthritis is the most common of the destructive autoimmune diseases, affecting about 300,000 Canadians, of whom about 70 percent are women. The disease, which is generally more dangerous and debilitating than osteoarthritis, causes the joints and connective tissue to become inflamed and deteriorate. “Patients with rheumatoid arthritis die 12 years sooner on average than the normal population,” says Dr. Keystone, also a professor of medicine at the University of Toronto.
The new therapies, which are currently being tested in clinical trials in Canada, the U.S. and Europe, are much more precise and selective than traditional treatments that globally suppress the entire immune system. They selectively target a specific hormone. One is known as TNF (tumor necrosis factor), which contributes to inflammation of the joints leading to arthritis. “People who have the disease produce too much of the TNF hormone in the joints,” explains Dr. Keystone.
Two of the most promising new therapies use different compounds to block the harmful action of TNE In the first, patients receive a monthly intravenous injection of genetically engineered antibodies that stop the TNF hormone from reaching the lining cells in the joints and causing inflammation. In the second, patients are injected twice a week with genetically engineered proteins known as soluble TNF receptors, which intercept the hormone before it can attach to the lining cells and cause damage. “By using these test-tube-produced TNF receptors, we are reproducing the body’s own defences against inflammation,” says Dr. Keystone.
Some rheumatoid arthritis patients take as many as 16 prescription drugs a day to keep symptoms in check and deal with the side effects of traditional drugs. The hope is that the new therapies may help patients like those with a severe form of the disease reduce their treatment regimens to just one drug.
Because the selective therapies are so new, only about 50 to 100 patients in Canada have been given these treatments to date. “I expect that the intravenous and soluble TNF receptors will be on the market within a year,” says Dr. Keystone. “More than half the patients with rheumatoid arthritis could be candidates for these new therapies.” The potential benefits aren’t limited to rheumatoid arthritis. Inflammation of body tissues is characteristic of most autoimmune diseases, so TNF blockers are now being tested on Crohn’s disease and other autoimmune disorders.