MONDAY, Nov. 4, 2002 (HealthDayNews) -- Rheumatoid arthritis sufferers who take the drug methotrexate, considered the gold standard of treatment, may find more relief by combining it with a newer drug called leflunomide.
That's the conclusion of a new study that appears in tomorrow's issue of the Annals of Internal Medicine.
"Fifty to sixty percent of patients find methotrexate not totally effective" at relieving the debilitating disease's symptoms, says study author Dr. Joel Kremer, of The Center for Rheumatology in Albany, N.Y. "A significant proportion of patients had good outcomes when leflunomide was added."
Rheumatoid arthritis (RA) is an autoimmune disease in which joints become inflamed, resulting in swelling and pain. The slow disintegration of the joint may eventually lead to immobility. According to the Arthritis Foundation, 2.1 million Americans suffer from RA.
The researchers conducted a 24-week trial at 20 centers in the United States and Canada that included 263 people with rheumatoid arthritis. The study was supported by a grant from Aventis Pharmaceuticals, which manufactures leflunomide.
All participants were given methotrexate. Half the volunteers (130) also received leflunomide, while the remaining 133 received a placebo.
At the end of the 24 weeks, 46 percent of those receiving leflunomide achieved at least a 20 percent improvement in their symptoms, as defined by the American College of Rheumatology criteria. This compared to 19.5 percent of the placebo group.
Many patients on leflunomide had significantly greater relief of symptoms. Slightly more than 26 percent reported a 50 percent improvement in symptoms, and 10 percent reported a 70 percent improvement, compared to 6 percent and 10 percent, respectively, for the placebo group.
Thirty-nine percent of the leflunomide recipients received 10 milligrams a day, 55 percent took 20 milligrams a day, and 6 percent took 10 milligrams every other day. The amount depended on tolerance of the drug and relief of symptoms.
Other drugs have been given with methotrexate before in the treatment of RA. But leflunomide is relatively new, and had not been previously tested with methotrexate, Kremer says.
"Every new drug that comes out must be studied with methotrexate," he says. "I'm pleased with the results. I think it fulfilled our hopes."
There are many unpleasant side effects associated with each drug. But the main concern was that the risk of liver toxicity -- a serious side effect associated with both drugs -- would be heightened by combining them. Only three patients on the combined therapy dropped out of the study due to problems with their liver function tests, Kremer says.
Dr. John Klippel, medical director of the Arthritis Foundation, says, "There's some concern that if you add two drugs, you may increase side effects or see new side effects you wouldn't see with either drug alone. This study does teach us that combining two drugs with risks of liver problems doesn't increase the risk."
Klippel laments the fact that, with all the treatments presently available for RA, "true remission and complete absence of symptoms is very rare."
For years, people have taken methotrexate alone, so it's good to find other drugs, such as leflunomide, that work well with methotrexate, he says.
"The optimal therapy of RA is continually changing. I think combination therapy represents an important advance for the treatment of people with rheumatoid arthritis," he says.
Kremer has just completed another, similar study showing that the benefits of taking methotrexate and leflunomide together is still found at the end of one year. That study has yet to be published.
What To Do
To learn more about rheumatoid arthritis, visit the Arthritis Foundation or the U.S. National Library of Medicine.
