WEDNESDAY, June 16, 2004 (HealthDayNews) -- Long-term relief from the pain of rheumatoid arthritis may soon be a reality.
In the June 17 issue of the New England Journal of Medicine, researchers from University College London report that the cancer drug rituximab, when taken alone or in combination with other rheumatoid arthritis drugs in a single course of two infusions, provided relief from the symptoms of rheumatoid arthritis for as long as 48 weeks.
"I think rituximab is going to be a promising addition to the treatments we have available for people with rheumatoid arthritis," said Dr. Leonard Serebro, a senior staff rheumatologist at the Ochsner Clinic Foundation Hospital in New Orleans.
Dr. Jonathan Edwards, lead author of the study and a professor of connective tissue medicine at University College London, said what's most exciting about this work is that it "completely changes our understanding of the cause of rheumatoid arthritis in that it shows that B cells are critically involved in the underlying process."
B cells, which are also known as lymphocytes, are an integral part of the body's immune system. When working properly, the immune system is only supposed to attack foreign matter, such as invading bacteria or viruses. In autoimmune diseases like rheumatoid arthritis, the body's immune system mistakenly turns against itself and begins attacking healthy tissue.
"The cycle underlying autoimmune diseases such as rheumatoid arthritis may be similar to a bug in a computer that makes it loop and crash," Edwards said in a statement. "B-cell targeted therapy is like rebooting the computer of your immune system to sidestep the bug."
More than 2 million people in the United States have rheumatoid arthritis, according to the Arthritis Foundation. Symptoms of the disease include joint pain and stiffness, fever, fatigue, limited range of motion, and redness of the skin.
Rituximab, sold under the brand name Rituxan, is what's known as a monoclonal antibody, which is a drug that targets a specific cell that's causing trouble. It is typically used to treat non-Hodgkin's lymphoma.
For the new study, Edwards and his colleagues randomly assigned 161 people with active rheumatoid arthritis to one of four treatments: oral methotrexate; rituximab; rituximab plus cyclophosphamide; or rituximab plus methotrexate. All of the study volunteers had taken methotrexate, a common rheumatoid arthritis medication, but had not achieved relief from their symptoms. Also, all were given a 17-day course of corticosteroids.
The researchers found that rituximab, when taken alone or in combination, provided greater relief of symptoms than methotrexate alone at both 24 and 48 weeks. For example, after 24 weeks, 43 percent of those on the rituximab-methotrexate combination and 41 percent on the rituximab-cyclophosphamide combination reported at least a 50 percent improvement in their symptoms compared to only 13 percent of the methotrexate group.
Edwards said the biggest benefit from this treatment was the long-lasting relief without a need for repeated treatments, which is standard with current therapies.
"On average, our patients need treatment every 15 months. For the most successful responders, it is every two to three years. Continued treatment in the sense of regular re-dosing is what this approach is designed to avoid."
Rituximab was well-tolerated. The only serious side effect was respiratory infection, but Serebro said that people with rheumatoid arthritis already have an elevated risk of infection because of the disease.
"The responses that were seen and the duration of the responses, coupled with the low side effects that were seen, were extremely encouraging," said Dr. Clifton O. Bingham III, a rheumatologist and director of the Seligman Center for Advanced Therapeutics at NYU-Hospital for Joint Disease. "In general, there's a lot of excitement surrounding rituximab for rheumatoid arthritis."
The experts caution, however, that this treatment needs more study. Serebro also noted that until it is FDA-approved for the treatment of rheumatoid arthritis, many insurance companies likely won't pay for the medication, which is expensive.
Bingham said the new study left several questions unanswered. First, he pointed out that fairly high doses of corticosteroids were given in this study. He said another trial needs to be done to see if rituximab needs to be given in combination with corticosteroids to be so effective, or if it could be given without the additional medication. Also, he said that while the people in this study achieved symptom relief, no objective measure, such as X-rays, were taken to assure that the disease was not continuing to progress.
Bingham and Serebro pointed out another exciting aspect of this therapy -- its potential for treating other autoimmune diseases, such as lupus.
"This has tremendous promise for all autoimmune diseases," said Bingham.
More information
To learn more about rheumatoid arthritis and its treatment, visit the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
