SAN DIEGO — For children with juvenile idiopathic arthritis, early treatment with a combination of methotrexate and etanercept leads to sustained clinically inactive disease more often than methotrexate alone, new research suggests.
"This ground-breaking study is the first to use clinically inactive disease as an end point," said lead investigator Carol Wallace, MD, from the University of Washington in Seattle. "It showed that clinically inactive disease is achievable if you treat early and aggressively."
Dr. Wallace presented an exploratory analysis of data from the Trial of Early Aggressive Therapy in Polyarticular Juvenile Idiopathic Arthritis (TREAT) here at the American College of Rheumatology (ACR) 2013 Annual Meeting.
TREAT was a double-blind placebo-controlled trial of 85 patients 2 to 17 years of age who had juvenile arthritis for less than a year.
The children were randomized to more aggressive treatment with methotrexate and etanercept, or to less aggressive treatment with methotrexate and placebo. All children received prednisolone tapered to 0 by week 17. The primary end point was clinically inactive disease at 6 months.
Dr. Wallace and her team evaluated time to achieve clinically inactive disease and how long it was sustained. They defined it as no joints with active arthritis, no elevated sedimentation rate, no uveitis, a Physician Global Assessment score of 0, and no fever, lymphadenopathy, or rash.
Patients were assessed using the Wallace criteria, at intervals of 1, 2, 4, 5, 6, 7, 8, 10, and 12 months. Participants in the less aggressive group who failed to achieve at least a 70% improvement in the signs and symptoms of juvenile arthritis (ACR Pedi 70) at 4 months and those who failed to reach clinically inactive disease at 6 months were switched to open-label treatment with the more aggressive regimen.
Median clinically inactive disease duration was longer in the more aggressive group than in the less aggressive group (139.5 vs 79.0 days; P = .016).
Clinically Inactive Disease
More patients who began therapy with the more aggressive than with the less aggressive regimen achieved clinically inactive disease at least once (71% vs 65%). However, 17 of the 28 who began therapy with the less aggressive regimen only achieved clinically inactive disease after switching to the more aggressive regimen.
"This is a phenomenal result in these children with a high burden of disease," Dr. Wallace said. Typically, about 5% of children with juvenile arthritis are rheumatoid-factor-positive, but in this study, 35% to 40% were, she explained.
Patients who started with the more aggressive therapy achieved clinically inactive disease a full month earlier than those who started with the less aggressive regimen. "Although 1 month may not seem like a long time, it is significant in a child's life," she noted.
The second important finding from the exploratory analysis was the number of follow-up visits during which clinically inactive disease was observed. Patients who started with the more aggressive regimen had more visits with clinically inactive disease than those who started with the less aggressive, even though they eventually switched to the more aggressive approach (32% vs 21%).
Children who had achieved ACR Pedi 70 at 4 months were more likely to attain clinically inactive disease than those who did not achieve an early response (86% vs 44%; P = .0001).
"The major predictor of achieving ACR Pedi 70 or clinically inactive disease was time to treatment. The earlier patients were treated, the more time they spent in clinically inactive disease," Dr. Wallace said.
Adverse events were not different than those reported in the parent study. In addition, there was no difference between treatment groups in serious adverse events, grade 3 and higher adverse events, or infections requiring systemic therapy.
The TREAT investigators plan to study whether these children can safety discontinue medications. Other studies suggest that at least 50% will flare when antirheumatic medications are stopped, Dr. Wallace pointed out.
"This is an exciting study that emphasizes the importance of early aggressive treatment," said news conference moderator Kam Nola, PharmD, MS, from the Lipscomb University College of Pharmacy in Nashville, Tennessee.
She noted that it is one of several studies that bring home the message that early aggressive therapy makes longer-term differences.
Timothy Beukelman, MD, from the University of Alabama at Birmingham, told Medscape Medical News he agrees.
"This study strongly suggests that all children with polyarthritis should be treated at the time of diagnosis with methotrexate at a minimum. A delay of even a few months appears to dramatically worsen short-term outcomes. The long-term benefits of the early use of TNF inhibitors remains to be seen," Dr. Beukelman said, "but these short-term results are encouraging."
This study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Wallace reports financial relationships with Amgen, Pfizer, and Novartis. Dr. Nola has disclosed no relevant financial relationships. Dr. Beukelman reports financial ties with Genentech and Pfizer.
ACR 2013 Annual Meeting: Abstract 790. Presented October 27, 2013.
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Cite this: Early Aggressive Therapy Succeeds in Children With Arthritis - Medscape - Nov 12, 2013.