'Biologic' Drug Fights Rheumatoid Arthritis

Rituximab could help patients with no other treatment option, experts say

FRIDAY, April 28, 2006 (HealthDay News) -- A new "biologic" therapy with a unique mechanism of action is proving effective in pushing painful rheumatoid arthritis into remission over the long term, researchers report.

The drug, rituximab (brand name Rituxan), has already proven safe and effective in treating non-Hodgkins lymphomas. But its ability to suppress immune B-cells may make it a valuable new weapon against rheumatoid arthritis as well.

"What rituximab does is give us another tool in our toolbox, particularly for people who have failed other treatments," said Dr. Hayes Wilson, chief of rheumatology at Piedmont Hospital, in Atlanta, and national medical advisor for the Arthritis Foundation.

Wilson was not involved in the study, which appears in the May issue of Arthritis & Rheumatism.

Rheumatoid arthritis is a chronic inflammatory autoimmune disease, in which the body's immune system attacks joint tissues, causing ongoing stiffness and pain. The exact causes of the disease remain unclear, and treatment effectiveness varies widely from patient to patient.

Many rheumatoid arthritis drugs are aimed at suppressing inflammatory T-cells, but experts say that less than half of patients respond to these therapies. Rituximab works on a wholly different mechanism, selectively depleting another immune-system player, the B-cell.

"That's important, because one of the cardinal signs of rheumatoid arthritis is what we call a 'positive rheumatoid factor,' " Wilson explained.

Rheumatoid factor is a kind of antibody long associated with severe rheumatoid arthritis. While most people have a rheumatoid factor level of well under 100, that number can soar in patients affected by the joint disease. "I have a cousin, for instance, who the very first time I saw him had a rheumatoid factor of 853," Wilson said. "He had really diffuse disease in every finger of his hands and every toe."

The key to rituximab's effectiveness is that it depletes B-cells, the major source of antibodies such as rheumatoid factor.

In the study, which was funded by drug makers Genentech, Biogen Idec and Hoffman-La Roche, researchers in Europe and the United States followed the six-month outcomes of 465 rheumatoid arthritis patients receiving either rituximab by infusion or a placebo. All of the patients had shown little response to other treatments.

The patients received two infusions two weeks apart of either 1,000 or 500 milligrams of rituximab, along with intravenous or oral steroids, or a placebo. All participants also received a standard therapy, methotrexate. Doctors checked the patients' progress every four weeks for a total of six months.

The study "confirmed the efficacy of rituximab," said lead researcher Dr. Paul Emery, professor of rheumatology and head of the Academic Unit of Musculoskeletal Disease at Leeds Teaching Hospitals Trust in Leeds, England.

Based on a standard 28-joint assessment of swelling and tenderness, about 55 percent of these tough-to-treat patients achieved real disease improvement after taking rituximab. That compared to just 28 percent of patients taking methotrexate plus a placebo.

Furthermore, rituximab worked just as well at a lower dose as it did at the higher dose. It also didn't seem to make a difference whether patients took long-term steroids along with their rituximab or not.

"Steroids are given along with the medicine to help your body accept this new protein that's coming into the body," Wilson explained. They are also given to help ease arthritic symptoms.

But the study found that patients taking rituximab didn't gain any added benefit from steroids, beyond the dose given at the time of the infusion. That's good news, Emery said, because "there are multiple side effects of steroids, mainly due to cumulative long-term effects rather than short-term actions."

According to Wilson, these heartening results open a new window for patients battling this crippling disease. "This is like everything else in medicine -- if you have something that is very difficult to treat, you want to have as many alternatives as possible," he said.

Wilson likened the doctor's job to a mechanic's as he works on a car: The more tools he has at hand, the better. "If you can have an extra wrench that can help you get deep inside the engine, that's great. And what rituximab can do is go deep inside the immune system and target this one specific nut or bolt -- a specific type of inflammatory cell, the B-cell."

He cautioned, however, that many rheumatologists may wait to use rituximab until its true worth has been proven in a much larger, controlled clinical trial.

That day may come soon, however. According to Emery, "longer trials are planned to optimize the use of this very interesting drug."

More information

For more on rheumatoid arthritis, head to the Arthritis Foundation.

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