Study Shows Low Doses of Rituxan as Effective as Higher Doses
By Salynn Boyles
WebMD Medical News
Reviewed By Ann Edmundson, MD
on Friday, April 28, 2006
Rituxan is the first drug to target a specific B immune cell, believed to play a role in inflammation in rheumatoid arthritis (RA) patients. It was approved two months ago by the FDA for use by rheumatoid arthritis patients who have failed other biologic treatments. Rituxan is administered as an infusion into a vein.
Patients taking low doses of Rituxan responded as well as those given higher doses, and the addition of steroids during treatment did not appear to improve outcomes.
All of the patients in the study had previously failed treatment with methotrexate or other DMARDs. About a third had been treated with biologic agents that work via a different pathway, such as the drugs Enbrel, Humira, and Remicade.
The findings suggest that patients may do equally as well on low doses of the drug as on high doses. But researcher Roy Fleischmann, MD, of the University of Texas Southwest Medical Center, says it is still too early to say this for sure.
"We don't yet know if responses last longer with higher doses or if the depth of response is better with different dosing," Fleischmann tells WebMD. "Studies involving larger numbers of patients are being done to answer these questions."
An estimated 3 million adults in the U.S. have rheumatoid arthritis, a progressive autoimmune disease that involves inflammation of the joints and surrounding tissues. Over the years, RA can destroy joints, ligaments, tendons, and even bone.
Biologic drugs that suppress inflammation-causing immune system cells, or cytokines, are new to the treatment of rheumatoid arthritis. While very expensive -- costing between $16,000 and $20,000 a year, according to one cost analysis -- they hold the promise of eliciting better outcomes than traditional RA treatments with fewer side effects.
The study of Rituxan included 465 patients with moderate to severe RA treated with Rituxan or placebo plus methotrexate -- with and without steroids.
The study is published in the May issue of the journal Arthritis and Rheumatism. It was funded by drug makers Genentech, Biogen, and Hoffmann-La Roche, which market the drug jointly. Genentech and Biogen are WebMD sponsors.
There were nine different treatment groups, designed to better understand which doses of drugs were most effective and whether adding steroids improved outcomes.
A total of 55% of the patients treated with the higher-dose Rituxan regimen showed a 20% or better improvement after six months, compared with 54% of patients on the low-dose regimen and 28% of patients taking a placebo.
Steroids, whether given in the vein or by mouth, didn't add any further improvement than Rituxan and methotrexate alone. But intravenous steroids given prior to Rituxan made the drug more tolerable.
Lower Doses, Fewer Steroids?
These finding suggest that high doses of steroids, which have many side effects when used long term, may not be needed in these patients.
Rheumatologist Simon Helfgott, MD, tells WebMD that this comes as no surprise. Helfgott treats rheumatoid arthritis patients at Brigham and Women's Hospital in Boston; he says about 40% of his patients are on biologics.
"Those of us who have been using this drug and following this understand that you don't need to give the whopping doses of steroids that were used in the early trials," he says.
He says Rituxan is emerging as a useful therapy for patients who fail treatment with the tumor necrosis factor (TNF)-targeting biologics, such as Enbrel, Humira and Remicade.
"The difference in its mode of action is intriguing," he says. "Some patients strike out on all of the anti-TNF agents. It will be interesting to see how they respond to this drug.""
SOURCES: Emery, P. Arthritis and Rheumatism, May 2006; vol 54: pp 1390-1400. Roy Fleischmann, MD, clinical professor of medicine, University of Texas Southwestern Medical Center, Dallas. Nermohamed et al., Drugs, 2005; vol 65: pp 661-694. Simon Helfgott, MD, rheumatologist, Brigham and Women's Hospital, Boston; associate professor of medicine, Harvard Medical School.
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