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Cancer Drug Gleevec May Ease Rheumatoid Arthritis

Mouse study suggests it might fight a range of autoimmune illnesses

THURSDAY, Sept. 14, 2006 (HealthDay News) -- The cancer "wonder" drug Gleevec, used to beat back leukemia and certain types of stomach tumors, also shows promise against autoimmune diseases such as rheumatoid arthritis.

"The data are very impressive, as impressive as anything I've ever studied," said study researcher and Stanford University rheumatologist Dr. William H. Robinson.

His team's findings were published online Sept. 14 in advance of their publication in the October print issue of the Journal of Clinical Investigation.

Robinson's group was screening drugs that might possibly help the estimated 50 percent of rheumatoid arthritis patients who do not adequately respond to current therapies.

Intrigued by case reports showing that rheumatoid arthritis symptoms improved in patients who received Gleevec (imatinib) as part of their cancer treatment, the researchers decided to test the drug in a mouse model of rheumatoid arthritis. These mice developed a disease similar to rheumatoid arthritis called collagen-induced arthritis.

Gleevec almost completely prevented the development of collagen-induced arthritis in healthy mice, Robinson's team reported. Compared to results in untreated mice, the drug also stopped disease progression and significantly reduced levels of bone destruction, inflammation, and tumor-like growth in and around the linings of joints.

The researchers also tested Gleevec on cells taken from the joints of humans with rheumatoid arthritis. They found that the drug shut down the cells' production of tumor necrosis factor-alpha (TNFa), a messenger molecule that drives rheumatoid arthritis-associated inflammation.

Gleevec also halted the proliferation of fibroblasts, the cells that cause tumor-like growth in joint linings.

"Gleevec inhibits several types of cells that are critical in rheumatoid arthritis," Robinson said. "But these cells are also critical in other diseases such as scleroderma, psoriasis and inflammatory bowel disease. Our results suggest a need for clinical trials of Gleevec in several human autoimmune diseases to see if it provides a benefit."

Although Gleevec is used in chemotherapy regimens, it's technically not a chemotherapy pill. It was designed to target gene mutations associated with chronic myelogenous leukemia (CLL) and certain types of stomach cancers, for which it has proven very effective.

"Overall, it's very well-tolerated," Robinson added. "Although there are some side effects such as bone-marrow suppression, it's not like conventional chemotherapy that causes hair loss and the sloughing of intestinal linings."

Rheumatoid arthritis is a chronic disease characterized by inflammation of the lining of the joints. It can lead to joint damage, resulting in pain, loss of function and disability, according to the Arthritis Foundation.

Because many rheumatoid arthritis drugs are administered by injection, Robinson said there's also been a "tremendous need" for therapeutic options in pill form. His research suggests that doses of Gleevec lower than those used in cancer treatment would benefit patients with autoimmune disease while causing fewer side effects.

Two case reports -- one involving a leukemia patient and another involving a patient with stomach cancer -- showed that treatment with Gleevec led to dramatic improvements in their rheumatoid arthritis symptoms, Robinson said.

And in an open-label trial of Gleevec, two rheumatoid-arthritis patients showed significant improvement, while a third patient showed only mild improvement, he said.

Because patients in open-label trials know they're receiving an experimental treatment, the results aren't conclusive because improvements may be related to a placebo effect. "You can't draw conclusions about whether or not something will work in human disease without a multi-center, placebo-controlled randomized, double-blinded trial," Robinson said.

Dr. Jonathan Edwards, a professor of connective tissue medicine at University College London, in England, doesn't share Robinson's enthusiasm for Gleevec as a possible treatment for rheumatoid arthritis. He also questioned the study's methodology.

"If we want to know whether or not Gleevec is helpful for rheumatoid arthritis, then the proper scientific approach is to ask the question directly," Edwards said. "You see if people with rheumatoid arthritis get better when given Gleevec."

"Giving Gleevec to mice that have been subjected experimentally to a form of arthritis which looks a bit like rheumatoid arthritis but has a completely different mechanism, is both irrelevant and in my view hard to justify ethically," Edwards added.

Robinson acknowleded that collagen-induced arthritis is not a precise reflection of human disease. "Generally, the mechanisms are similar, but it's far from a perfect model," he said.

Still, he remains hopeful that any forthcoming clinical trial will confirm that Gleevec is as effective in treating arthritic humans as it was in helping arthritic mice.

"It's an exciting time in autoimmunity, because we've had seven-plus drug approvals for rheumatoid arthritis in the past five to 10 years, and it's really changed clinical practice," he said.

"Hopefully, drugs such as Gleevec will take us to the next level where maybe we can treat the disease in people who currently don't adequately respond to other therapies," Robinson said.

More information

There's more on rheumatoid arthritis at the Arthritis Foundation.

SOURCES: William H. Robinson, M.D., Ph.D., Stanford University, Stanford, Calif.; Jonathan Edwards, M.D., professor, Connective Tissue Medicine, University College London, England; Sept. 14, 2006, early online edition, Journal of Clinical Investigation
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