November 8, 2011 (Chicago, Illinois) — Early aggressive treatment of polyarticular juvenile idiopathic arthritis (JIA) improves disease symptoms and the percentage of patients with inactive disease and clinical remission, according to results from the Trial of Early Aggressive Therapy in Polyarticular Juvenile Idiopathic Arthritis (TREAT), which were presented here at the American College of Rheumatology (ACR) 2011 Annual Meeting.
The benefit of early aggressive treatment has been demonstrated in adults with rheumatoid arthritis, but until now, few studies have focused on children. An estimated 300,000 children in the United States have been diagnosed with JIA. Polyarticular JIA is the most severe form of JIA, and accounts for a great deal of associated morbidity.
"This is the first randomized double-blind clinical trial using inactive disease and remission as the main outcomes. It is not enough for treatments to improve JIA, we need to treat with the goal of disease remission," stated lead author Carol Wallace, MD, professor of pediatrics at the Children's Hospital and Regional Medical Center, Seattle, Washington. "This remarkable study demonstrates the importance of early aggressive therapy for children with polyarticular JIA," she noted.
The multicenter, prospective, double-blind, placebo-controlled TREAT randomized 85 children from 15 centers to etanercept plus methotrexate plus prednisolone (combination group, with the etanercept upfront) or to methotrexate plus 2 placebos (methotrexate group) for up to 12 months. At baseline, median age was 11.1 years and median disease duration was 4.1 months. Sixty-nine percent of the patients were antinuclear-antibody-positive and 36% were rheumatoid-factor-positive.
At 4 months, patients who achieved at least a 70% response, assessed by ACR pediatric 70 (70% improvement in symptoms), continued on their blinded treatment; those who did not were switched to open-label combination therapy. At 6 months, patients who reached the primary end point of clinically inactive disease continued on their treatment; those who did not were switched to open-label combination therapy for another 6 months.
At 4 months, ACR pediatric 70 was achieved in 30 of 42 patients (71%) in the combination group and in 19 of 43 patients (44%) in the methotrexate group. At 6 months, clinically inactive disease was achieved in 17 of 42 patients (40%) in the combination group and in 10 of 43 patients (23%) in the methotrexate group.
Dr. Wallace reported that the end point of clinically inactive disease was based on stringent criteria, including no affected joints, no symptoms, no eye involvement, normal sedimentation rate, and physician's global assessment of no active arthritis.
"Nearly one third of patients overall achieved clinical inactive disease after 6 months of therapy, which is a remarkable result," Dr. Wallace said.
Disease duration at baseline was the best predictor of clinically inactive disease at 6 months, she said. The odds of achieving clinically inactive disease increased by 30% for each month earlier that treatment was initiated after the onset of symptoms (P = .011).
At 6 months, patients in both groups had significantly improved physician's global assessment of disease activity, parent's global assessment of wellbeing, number of joints with arthritis, and number of joints with limited motion.
At 12 months, clinical remission (defined as 6 months of inactive disease) was achieved in 21% of the combination group and 7% of the methotrexate group.
Safety and tolerability were similar in both groups, as were grade 3 or higher adverse events. Three serious adverse events resolved without sequelae.
"This study sets a new standard for treatment, response, and outcomes for children with polyarticular JIA. Achieving 70% improvement by 4 months and inactive disease by 6 months are achievable goals. One of the most remarkable findings is the importance of early treatment. There does appear to be a window of opportunity for JIA, as there is for rheumatic arthritis," Dr. Wallace said.
Stacy Ardoin, MD, from Ohio State University Medical Center in Columbus, told Medscape Medical News that "we need more data on optimal therapy for JIA. We know that early aggressive treatment improves outcomes in adults, but this hadn't been studied in children. It isn't clear whether it is best to initiate treatment with less-intensive therapy and then add biologics, or to start with our strongest therapies."
"Although this study did not meet its primary end point in terms of achieving complete remission and clinically inactive disease at the set timepoint of 6 months, the signals were for improved response in the [combination group]. We await radiographic outcomes," she said.
The fact that there was no increase in infections in the combination group "gives me more confidence in using this aggressive treatment upfront in children," Dr. Ardoin noted.
The take-away point from this study, according to Dr. Ardoin, is that the data do not add up to a definite mandate for treating all children with polyarticular JIA with early aggressive therapy. However, "physicians who choose this approach can be reassured by the trend toward improved disease control and the safety data so far," she said.
Dr. Wallace reports receiving financial support from Amgen, Pfizer, and Bristol-Myers Squibb. Dr. Ardoin has disclosed no relevant financial relationships.
American College of Rheumatology (ACR) 2011 Annual Meeting; Abstract 721. Presented November 8, 2011.
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