NIH News Release
NATIONAL INSTITUTES OF HEALTH
National Institute of Arthritis and
Musculoskeletal and Skin Diseases

FOR IMMEDIATE RELEASE
Thursday, December 14, 2000
Contact: Kelli Carrington
Office of Communications
and Public Liaison
(301) 496-8190

New Drug Studies Show Promise for Reducing Joint Damage in Rheumatoid Arthritis

Two new research studies in the November 30 issue of The New England Journal of Medicine reflect a rheumatoid arthritis (RA) research effort moving at a breathtaking pace, according to experts in the field. One study has shown that a combination of the drugs infliximab (RemicadeTM) and methotrexate significantly reduced the symptoms of RA and halted progression of joint damage over methotrexate treatment alone in a 54-week trial of 428 patients. The other reveals that etanercept (EnbrelTM), when compared to methotrexate alone, also arrested joint damage and more rapidly decreased symptoms in a 12-month trial of 632 patients.

Peter E. Lipsky, M.D., scientific director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and lead author of the infliximab study, remarked that "in the last 2 years, rheumatoid arthritis research has moved further than in the last 30." There has been much excitement, he said, about the wealth of new treatments now becoming available and the potential to prevent and heal structural damage to the joints of people with RA.

Dr. Lipsky led the infliximab study while at the University of Texas Southwestern Medical Center in Dallas. According to the paper, nearly 52 percent of the patients taking the infliximab/methotrexate combination showed symptom reductions, compared with 17 percent of methotrexate-only patients. X-ray examination showed that joint damage was halted in those given the drug combination, and in 40 to 55 percent of patients, joint damage decreased, implying that some damage had been repaired. Joint damage proceeded in the group given only methotrexate. The combination, which was well-tolerated, also significantly improved quality of life. Dr. Lipsky presented an abstract at this year's American College of Rheumatology meeting showing that benefit of the drug combination was sustained during the second year of the study.

In the second study, led by Joan Bathon, M.D., at Johns Hopkins University, Baltimore, etanercept was compared to methotrexate in patients with early disease. Etanercept acted more rapidly than methotrexate, and also resulted in fewer adverse events. The rate of joint damage, as measured by X-rays, was significantly reduced in the etanercept group compared to the methotrexate-treated group. After one year of treatment, 72 percent of the etanercept patients had no progression in erosions compared to 60 percent of the methotrexate-treated patients. "These results emphasize the importance of early treatment to slow and, in some cases, prevent joint damage," said Dr. Bathon.

Stephen I. Katz, M.D., Ph.D., director of the NIAMS, which has funded much of the basic research contributing to these discoveries, said "These studies represent a milestone in curtailing disease progression in people living with RA. We applaud this new evidence that the severity of joint damage from this debilitating disease can be greatly reduced in many patients."

Infliximab and etanercept belong to a class of drugs called "biological response modifiers" that neutralize the inflammatory protein "tumor necrosis factor-greek symbol alpha" The drugs act by blocking the activity of destructive inflammatory cells that cause the joint damage characteristic of RA.

Methotrexate is a drug that suppresses the immune system, and has been used historically in higher doses for cancer therapy. It was approved over a decade ago for treating certain types of arthritis and skin conditions.

RA is an inflammatory disease that causes pain, swelling, stiffness, and progressive loss of function in the joints. It may also cause fatigue, occasional fever, and a general sense of not feeling well. In some cases, the internal organs and systems can become involved and ultimately damaged. An estimated one percent of the adult U.S. population have the disease, and about two to three times as many women as men.

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) is a component of the National Institutes of Health. The mission of the NIAMS is to support research into the causes, treatment and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and clinical scientists to carry out this research, and the dissemination of information on research progress in these diseases. For more information about NIAMS, call our information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS Web site at http://www.nih.gov/niams.

RemicadeTM is a trademark of Centocor, Inc., Malvern, Pa. EnbrelTM is a trademark of Immunex Corporation, Seattle, Wash.

To interview Dr. Joan Bathon, contact Marjorie Centofanti, director of media relations, Johns Hopkins University School of Medicine, at 410-955-8725.


References:
Lipsky P, Van Der Heijde D, St. Clair E, et al. Infliximab and methotrexate in the treatment of rheumatoid arthritis. NEJM 2000;343(22):1594-1602. Bathon J, Martin R, Fleishmann R, et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. NEJM 2000;343(22):1586-1593.