Rheumatoid Arthritis Added to Gleevec Targets -- in Mice

STANFORD, Calif., Sept. 14 -- Gleevec (imatinib), the targeted leukemia drug, appears to prevent and reverse rheumatoid arthritis in a mouse model, researchers here reported, apparently by inhibiting proteins involved in inflammation.

The finding hints that the tyrosine kinase inhibitor - approved for the treatment of chronic myelogenous leukemia and for gastrointestinal stromal tumors - might also be beneficial for a range of human autoimmune diseases, according to William Robinson, M.D., Ph.D., of Stanford.

But Dr. Robinson said that researchers still must discover which of the kinases blocked by Gleevec are key to the clinical benefit seen in the mice and even more importantly must test whether the same effect will be seen in humans.

"A lot of things work in animal models that don't work in the clinic," he noted.

But in mice, treatment with Gleevec prevented the onset of collagen-induced arthritis (CIA), he and colleagues reported online today in the Journal of Clinical Investigation. The study will appear in the October print edition of the journal.

In a series of experiments, mice were treated with two different doses of Gleevec or placebo, starting before injections of bovine collagen to induce arthritis. In the placebo group, more than 90% of the mice developed CIA, compared with 50% of animals getting low-dose Gleevec and 20% of those getting a high dose. The low and high doses were 33 and 100 mg/kg, respectively.

While the prevention was interesting scientifically, "it's not the real world," Dr. Robinson said. "People don't come to you until they have established arthritis."

And when the researchers induced CIA and then followed up with Gleevec treatment, they found significant treatment benefits, based on a visual scoring system and measurements of the thickness of the animals' paws.

"In all three measures, (Gleevec) came out very robustly providing benefit," Dr. Robinson said.

Specifically:

• Mice with established clinical arthritis - with an average visual score of four and a paw thickness of 2.4 millimeters -- were randomized to low- or high-dose Gleevec or placebo.
• Ten days after the start of treatment, placebo mice had an average visual score of seven, but the mice on either dose of Gleevec remained at about four. The difference was significant at P