ACR: Aggressive Initial Therapy Can Send Rheumatoid Arthritis Into Remission

WASHINGTON, Nov. 14 -- Early aggressive treatment with a combination of drugs can drive rheumatoid arthritis into drug-free remission in some patients, Dutch researchers said here.

"Hit them early and hit them hard," advised Cornelia Allaart, M.D., of Leiden University Medical Center.

Given the right combination of drugs in initial therapy, about one in eight patients appears to be able to stop the medications entirely within three years, Dr. Allaart reported at the American College of Rheumatology meeting.

The finding comes from the long-running BeSt study, whose name comes from the Dutch words for treatment strategies. In the study, 508 patients were randomized to one of four treatment paradigms -- sequential monotherapy with standard drugs, monotherapy escalating to combination treatment in the event of failure, initial combination therapy using prednisone and another medication, or initial combination therapy with Remicade (infliximab) and methotrexate.

The initial combination therapies proved superior in terms of improvement in functional ability and slowed progression of joint damage, Dr. Allaart said. But it was patients in the fourth arm who were able to stop therapy with no penalty.

After two years of the study, Dr. Allaart said, 67/120 patients (56%) were able to stop the Remicade and begin tapering methotrexate to "maintenance levels" of 10 mg/week. After another year, she said, 15% of the patients had also stopped methotrexate.

"They are now without any drug and also without any clinical signs or symptoms," Dr. Allaart said. "This is a very new approach to therapy," she said, adding the study still needs longer follow-up.

Only four of the original 67 responders in the arm had to increase methotrexate after a disease flare, she reported.

It is possible that joint damage could be progressing despite the lack of symptoms, Dr. Allaart said, but x-rays of the patients in remission show no sign of that "even though at baseline more than half had some damage on x-rays (59% had erosive disease)."

Dr. Allaart said the finding should be translated into clinical practice. The study had a "very large body of patients and they had very active disease," she said, so that the finding is relatively robust.

"If you see that these patients are reacting so well, (the approach) should be considered in daily practice," she said.

On the other hand, she said, financial constraints -- even in countries with government-supported drug plans -- are likely to mean the approach will not be put into wide practice. She said doctors need to press governments to improve reimbursement programs.

"It's a very interesting trial, but I'm not as convinced as they are that by giving infliximab and methotrexate you induce 15% at the end of three years who don't have any active disease," commented Stanley Cohen, M.D., of the University of Texas Southwestern Medical Center at Dallas, who was not involved with the study.

It's also possible that the patients who went into remission would have done so anyway, even if treated just with methotrexate, he said.

Like Dr. Allaart, he also sounded a financial warning: "I don't think around the world we have the resources to treat all patients with a biologic and methotrexate."

On the other hand, Dr. Cohen said, if delaying symptoms is shown to make a difference in the eventual outcome of the disease, doctors will have little choice: "We're going to intervene sooner rather than later."