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 previously untreated children with juvenile idiopathic arthritis (JIA) (n = 109) 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. Using a blood sample, clinicians might be able to know "whether or not, when a child walks in, is methotrexate going to be appropriate," she noted.
Dr. Moncrieffe noted that serum MRP8/14 is "relatively easy to measure" and that samples do not require cold storage, making laboratory transport and processing easier. High levels of MRP8/14 were shown to be the most strongly predictive factor in a JIA patient achieving an ACR score of 50 or higher at 6 months on methotrexate, the researchers found, with likelihood of achieving ACR 50 or better seen 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 ACR 50 or higher response to methotrexate. High serum levels were predictive of methotrexate success regardless of the type of JIA or age at onset; however, patients with systemic JIA were excluded from the study.
Investigator Dr. Marieke Otten of Erasmus University Medical Center in Rotterdam 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 colleagues enrolled 262 patients who had never been prescribed a biological agent to control their disease before starting etanercept. The patients had been enrolled as the Dutch Arthritis and Biologicals in Children register, which has since 1999 kept data on all Dutch JIA patients using etanercept. The register is funded in part by an unconditional grant from Abbott.
They then 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 be predictive of 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," Dr. Otten said at the conference. "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 ACR 50 response or better but did not reach inactive disease, and the last third (34%, n = 88) reached a poor response, defined as less than ACR 50, or stopped etanercept early because of ineffectiveness or adverse effects, she said.
Children who began treatment with etanercept before trying disease-modifying anti-rheumatic drugs (DMARDs) saw more improvement than those who had been on them previously, the investigators learned. The finding that children who had taken fewer DMARDS did better was "really important," as it indicated "the earlier and more aggressively we treat, the better the patients get," she said.
Girls and children with systemic-onset JIA were more likely to fare poorly on etanercept, Dr. Otten and her colleagues found. However, about a quarter of children with systemic onset were able to achieve inactive disease after 15 months of treatment.
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. University College London has filed a patent relating to methods for predicting effectiveness of drug treatment for arthritis. Dr Moncrieffe is an inventor on this patent application.
Some funding for the study came from Abbott and Pfizer, Dr. Otten disclosed.