Children on the multi-drug regimen first became symptom-free about five months after starting therapy – a month earlier than the methotrexate-only group. Methotrexate-only patients who still had symptoms after six months were switched to the more-aggressive treatment. Even then, they didn’t have as many periods of clinical inactive disease as those who received the combination therapy from the start.

What’s more, children who by four months improved 70 percent or more had a higher number of symptom-free days (140 days) compared to those who didn’t hit this early benchmark for improvement (79 days).

Among the 12 kids who achieved remission (no symptoms for six continuous months), all of them had hit the early benchmark for improvement. Of those 12, nine were in the aggressive therapy group and three received methotrexate alone.

It’s not known how long children with juvenile arthritis must continue taking powerful medications to stay symptom-free. Dr. Wallace points to research showing that young patients continue to have abnormal immune systems, even when they have no signs of active disease.

The long-term safety of such an aggressive regimen is also not fully known. During the study, some children developed infections that required treatment and others dropped out due to the severity of their disease. Dr. Wallace says a number of patients would also “go in and out of active disease,” with arthritis flaring and then subsiding in a single joint.

Still, she says the evidence shows that early, aggressive treatment offers the best hope for children with JIA.

Thomas Lehman, MD, chief of pediatric rheumatology at Hospital for Special Surgery in New York City, is not so sure.

He says that although the study demonstrates the well-known fact that early aggressive treatment of children with JIA is a “key determinant of outcome,” the study itself is flawed.

“[It utilized] a study arm that included steroids plus an anti-TNF agent [etanercept] plus methotrexate versus methotrexate alone. This study design made it impossible to ascertain whether the rapid improvement was due to early use of steroids or the anti-TNF agent,” he explains. “In addition, a large proportion of pediatric rheumatologists are avoiding the toxicity associated with methotrexate by utilizing an anti-TNF agent alone, but unfortunately, this regimen wasn’t studied.”