Major Finding: Serum levels of the inflammatory protein MRP8/14 were elevated in 96% of children with JIA who went on to respond well to methotrexate.
Data Source: Data from a Dutch register of 109 children with JIA.
Disclosures: Dr. Moncrieffe's study was sponsored by Sparks-UK, the Big Lottery Fund, Arthritis Research U.K., and the Great Ormond Street Hospital Children's Charity.
BRUGES, BELGIUM – Blood levels of an inflammatory protein have been found to be strongly predictive of how well a child with juvenile idiopathic arthritis will do on methotrexate, U.K. researchers have learned.
Children with higher serum levels of myeloid-related protein 8/14 (MRP8/14) were seen to respond considerably better.
The MRP8/14 findings came from Sparks CHARMS (Childhood Arthritis Response to Medication Study), which used a cohort of 109 previously untreated children with JIA to assess predictors of success with methotrexate. The findings represent a step toward the “ambitious goal” of personalized medicine for JIA, said Halima Moncrieffe, Ph.D., of University College London (Pediatr. Rheum. 2011;9[Suppl. 1]:O10), who presented the data on MRP8/14. Dr. Moncrieffe noted that serum MRP8/14 is “relatively easy to measure,” and that samples do not require cold storage.
High levels of MRP 8/14 were shown to be the most strongly predictive factor in a JIA patient achieving an American College of Rheumatology score of 50 or higher at 6 months on methotrexate, with the likelihood of achieving ACR50 or better increasing with every 500-ng/mL serum increase. Of patients with MRP8/14 levels above 3,000 ng/mL at baseline, 96% went on to achieve an ACR50 or higher response to methotrexate. High serum levels were predictive of response to methotrexate regardless of the type of JIA or age at onset; however, patients with systemic JIA were excluded from the study.
Dr. Marieke Otten of Erasmus University Medical Center in Rotterdam (the Netherlands) presented data on clinical indicators of treatment success or failure with etanercept in a cohort of JIA patients (Pediatr. Rheum. 2011;9[Suppl 1]:O28). Ongoing research is examining the usefulness of baseline MRP levels as response predictors, she noted.
Dr. Otten and her associates enrolled 262 patients who had never been prescribed a biologic agent to control their disease before starting etanercept. The patients had been enrolled in the Dutch Arthritis and Biologicals in Children register, which since 1999 has kept data on all Dutch JIA patients using etanercept. The register is funded in part by an unconditional grant from Abbott.
They collected baseline clinical data using the physician's global assessment of disease activity and children's health assessment questionnaire scores. The investigators' goal was to identify clinical predictors of poor response to etanercept and which clinical characteristics might predict adverse events during treatment. However, the study failed to show any significant associations for adverse effects.
“It has been proven that etanercept is highly effective in juvenile idiopathic arthritis, and under current treatment strategies inactive disease seems to be a realistic treatment goal,” said Dr. Otten. “However, a still-substantial proportion of patients do not reach the goal of inactive disease.” About a third of the patients in Dr. Otten and colleagues' study (32%, n = 85) reached clinically inactive disease after 15 months on etanercept. Another third had an ACR50 response or better but did not reach inactive disease, and the last third (34%, n = 88) reached a poor response, defined as less than ACR50, or stopped etanercept early because of ineffectiveness or adverse effects, she said.
Children who began etanercept treatment before trying disease-modifying antirheumatic drugs improved more than those who had been on them previously. This finding was “really important,” as it indicated “the earlier and more aggressively we treat, the better the patients get,” she said.