Lower Doses of Rheumatoid Arthritis Drugs May Work for Some

Some people in the early stages of rheumatoid arthritis may be able to safely lower their medication doses once their symptoms are well under control, a new study suggests.

In a clinical trial, British researchers found that many patients were able to remain in remission for months after their doctors lowered their doses of the drugs methotrexate and Enbrel (etanercept).

What's more, some continued to do well when they were taken off the drugs altogether, the researchers said in the Nov. 6 issue of the New England Journal of Medicine.

The findings suggest it's "reasonable" to lower, or even stop, certain patients' medication doses, wrote the researchers, led by Dr. Paul Emery of the University of Leeds.

But experts not involved in the study stressed that there are some big unknowns.

For one, it's not clear which patients would likely do well if their drug doses were cut, and which ones might see their symptoms flare again, said Dr. David Borenstein, a rheumatologist and professor of medicine at George Washington University in Washington, D.C.

Those are questions researchers are actively trying to answer, Borenstein said. There could, for instance, be indicators (so-called "biomarkers") -- such as proteins in the blood -- that would help predict a patient's likelihood of doing well with a treatment change.

"We're trying to fine-tune individual patients' care, and figure out who can, in fact, go without a medication and who needs to continue it," Borenstein said.

But for now, he said, people whose rheumatoid arthritis is well-controlled should probably stick with their treatment plan, unless there's a "compelling reason" to change it.

"My feeling is, don't mess with success," Borenstein said.

Rheumatoid arthritis arises when the immune system mistakenly attacks and inflames the lining of joints throughout the body, leading to pain, swelling and stiffness. Over time, that inflammation can cause irreversible damage to the joints.

Because of that, early treatment is key, Borenstein said.

Patients in the current study were all in the early stages of the disease. Initially, 222 patients spent a year on weekly injections of Enbrel, along with the oral drug methotrexate. Of that group, 193 saw their symptoms go into remission by the one-year mark, and they entered the next phase of the study.

At that point, Emery's team randomly assigned them to one of three groups: One had their drug doses lowered, one stopped taking Enbrel, and one stopped both medications.

After about eight months, the investigators found that 63 percent of patients on the lowered doses were still in remission. That compared with 40 percent of those on methotrexate alone, and 23 percent of those taking neither drug.

In a final step, Emery's team had patients who were still in remission stop all treatment. About six months later, some remained in remission; those who'd been on lower doses of Enbrel and methotrexate fared the best -- with 44 percent still in remission.

Enbrel is one of a group of rheumatoid arthritis drugs that block an immune system protein called TNF, which helps curb inflammation and prevent joint damage. Methotrexate is an older drug that also fights inflammation.

There are good reasons to figure out whether patients can take breaks from the drugs, or cut the doses, according to Borenstein.

TNF blockers are very expensive, he pointed out, and both medications can have significant side effects.

"But," Borenstein said, "the concern is, that could lead to structural damage [in the joints], and there's no way for us to reverse that."

Another rheumatologist who reviewed the study agreed that important questions remain.

"This doesn't give us enough guidance to make broad-based recommendations," said Dr. Diane Horowitz, of North Shore University Hospital in Manhasset, N.Y. "This is a first step."

"I'm not saying we should never lower patients' doses," she added. And in certain cases -- such as when a patient can't tolerate the medications' side effects -- the current findings offer useful information.

But, she said, longer-term studies are needed before any general recommendations could be made.

Enbrel maker, Pfizer Inc., funded the study, and several of the researchers work for the company.

More information

The U.S. National Institute of Arthritis and Musculoskeletal and Skin Diseases has more on rheumatoid arthritis.