Again, childhood data show similar findings. A study reported at the 2009 ACR annual meeting randomized 60 DMARD-naive JIA patients with just 6 weeks’ disease duration to methotrexate, methotrexate plus infliximab, or a combo of methotrexate, sulfasalazine, and hydroxychloroquine. At 6 months, an ACR Pedi 75 response occurred in 100% of the double therapy group, 65% of the triple therapy group, and 10% of the methotrexate-only group. By 54 weeks, 68% of the double therapy, 40% of the triple therapy, and 25% of the methotrexate groups had inactive disease.
All of these encouraging data lead to the TREAT (Trial of Early Aggressive Therapy) in JIA trial, the results of which Dr. Carol Wallace is eagerly awaiting. The yearlong study randomized 85 children with polyarticular or extended oligoarticular JIA to one of two aggressive treatment regimens. Because all of the subjects had a disease duration of less than 12 months, TREAT may provide answers about optimal timing as well as optimal therapy.
The study is being conducted by CARRA (Childhood Arthritis and Rheumatology Research Alliance). Founded by researchers, CARRA conducts investigator-initiated clinical trials not only for JIA, but also for other childhood rheumatic diseases (www.carragroup.org). CARRA now comprises 92 pediatric rheumatology centers and more than 300 clinician members all over North America.
TREAT was conducted at 15 CARRA sites. Both weekly treatment arms included subcutaneous methotrexate at 0.5 mg/kg. Group A also received placebo etanercept, folate, NSAIDs as necessary, and a placebo prednisone taper. Group B received, in addition to methotrexate, weekly subcutaneous injections of etanercept at 0.8 mg/kg; folate; NSAIDs as needed; and a 4-month prednisone taper that started at 0.5 mg/kg.
The study’s primary end point is the rate of inactive disease at 6 months. Secondary end points include the rate of ACR Pedi 70 by 4 months; clinical remission on medication by 12 months; safety of the treatment, and MRI of the knee to show potential biologic changes associated with active and inactive disease.
The children’s mean age was 11 years and their mean disease duration was just over 4 months. They had a mean of 22 active joints and a mean erythrocyte sedimentation rate of 37. Their mean Physician Global Assessment score was nearly 7. Most of the children (69%) were positive for antinuclear antibodies; 36% were rheumatoid factor positive.
The last subject visits have just occurred, and so full data analysis has not been completed. Dr. Wallace said that 77 patients finished out the pivotal first 6 months of the trial. At that point, those who achieved a state of inactive disease continued on their assigned treatment arm until the end of the trial, or until they had a flare. Those who still had active disease at 6 months could opt for up to 6 months of open-label etanercept plus methotrexate and a prednisone taper, or up to two intra-articular injections while continuing on their blinded treatment. If they then experienced a flare, they discontinued the trial.
By the end of October, 67 patients (77%) had completed 12 months of the trial. Dr. Wallace and her coinvestigators expect to release the results in the first quarter of 2011.
Despite its relatively small size, she said, TREAT could be practice transforming. "Whatever the result, we plan to deploy this treatment as quickly as we can in clinical practice. That’s actually the beauty of the CARRA network. We can, through our members, make a standard of care based on data. And that’s what this study is all about – finding evidence. We must continue to look for evidence that supports the best way to treat JIA."
Although Amgen supplied the etanercept for TREAT, the study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health. Dr. Wallace has no financial disclosures with regard to the study.