Methotrexate Best for Juvenile Arthritis

Methotrexate still appears to be best for treating juvenile rheumatoid arthritis, but a newer medication, Arava, is a very good second choice.

In an international study involving kids and teens with a particularly severe form of juvenile rheumatoid arthritis, almost 90 percent showed significant improvement with high doses of methotrexate for 16 weeks.

Similar responses were seen in about 70 percent of children treated with Arava. Sanofi-Aventis, which markets Arava, paid for the study, which is published in the April 21 issue of The New EnglandJournal of Medicine.

"A higher percentage of patients responded to methotrexate, so this would be the medication to try first in children, but [Arava] is a good alternative for patients where methotrexate doesn't work or isn't tolerated," says rheumatologist and researcher Earl Silverman, MD, of The Hospital for Sick Children in Toronto.

Activities Improve

Between one and four children out of every 1,000 have juvenile rheumatoid arthritis. In those with a milder form of the disease symptoms often go away with minimal treatment over time. But in those with a particularly aggressive form, known as polyarticular juvenile rheumatoid arthritis, pain is often severe and long lasting and can lead to joint deformity.

Standard anti-inflammatory pain relievers are often not enough for those with severe juvenile rheumatoid arthritis. Methotrexate is often prescribed for these children.

In this study, Silverman and colleagues compared children with polyarticular juvenile rheumatoid arthritis who took either Arava or higher-than-normal doses of methotrexate for almost a year.

The methotrexate dose -- given weekly -- was 0.5 milligrams per kilogram of body weight. The maximum dose was 25 milligrams. So for a 70 pound child, the starting dose would be about 15 milligrams.

After four months, 89 percent of the children treated with high-dose methotrexate showed improvements in activities, such as walking, dressing, and eating, compared with 68 percent of the children taking Arava.

Better Response Than Seen in Adults

The responses were greater than those seen in adult studies. Improvements were maintained among patients who kept taking the drugs for eight more months.

"We found that the higher dose of methotrexate was as safe as lower doses, so it makes sense to start patients off with higher doses," Silverman tells WebMD.

Children who fail to respond to methotrexate are put on treatments called biologics like Remicade and Enbrel. But the study indicated that these nonrespondent patients may benefit from treatment with Arava.

"It has changed my practice, because I now start patients on higher doses of methotrexate and I am also inclined to try Arava before going on the biologics," Silverman says.

Early Treatment Important

The findings also suggest that early, aggressive treatment is important. Most of the patients in the study had been diagnosed for only a few months.

Pediatric rheumatologist Norman Ilowite, MD, tells WebMD that doctors in the field have gotten the message, and most now use methotrexate early in the treatment of children with polyarticular juvenile rheumatoid arthritis.

He adds that the newly published study does not convince him that methotrexate is more effective than Arava because the researchers used such high doses of methotrexate. Ilowite is chief of the division of pediatric rheumatology at Schneider Children's Hospital in New York and a professor of pediatrics at Albert Einstein College of Medicine.

"I think the jury is still out as to which one is better," he says.

By Salynn Boyles, reviewed by Michael W. Smith, MD

SOURCES: Silverman, E. The New England Journal of Medicine, April 21, 2005; vol 352: pp 1655-1666. Earl Silverman, MD, departments of pediatrics and immunology, University of Toronto. Norman Ilowite, MD, chief of the division of pediatric rheumatology, Schneider Children's Hospital; professor of pediatrics, Albert Einstein College of Medicine, New York.