BRIGHTON, ENGLAND – The pretreatment measurement of a serum protein could help determine if young children with juvenile idiopathic arthritis are likely to respond to methotrexate.
Data from the ongoing SPARKS–Childhood Arthritis Response to Medication Study (CHARMS) show that the pretreatment serum levels of myeloid-related protein (MRP) 8/14 are higher in children who will respond well to treatment with the disease-modifying antirheumatic drug, but levels are lower in those who are less likely to benefit.
The finding holds promise for the development of a simple predictive test that could be used to avoid giving unnecessary and prolonged methotrexate treatment to the estimated 30% of children who are unlikely to respond to the DMARD.
“Essentially what we are trying to do is give effective treatment at clinical presentation,” said Halima Moncrieffe, Ph.D., a research fellow at University College of London (UCL) Institute of Child Health. Dr. Moncrieffe noted that giving methotrexate to all children at diagnosis possibly represents a missed opportunity, as children who wre unlikely to respond face worsening arthritisanefore it is recognized that the disease-modifying antirheumatic drug has no great effect.
SPARKS-CHARMS thus is looking for biologic, genetic, or psychological factors that could help predict and explain the response to treatments for JIA. The overall study involves more than 800 children who are being treated at the Great Ormond Street Hospital in London. At enrollment, and before any treatment, standard assessments are made and a blood sample is taken for analysis. Assessments are then repeated 6 months after treatment.
Dr. Moncrieffe presented findings on 109 study participants who had been treated with methotrexate from a mean age of 5.2 years and had a mean disease duration of 0.9 years before treatment initiation; 70% were female.
After the researchers excluded children with systemic disease because they had higher inflammatory protein levels than did other JIA subtypes, the results showed higher pretreatment concentrations of MRP8/14, also known as calprotectin or S100A8/A9, in the blood samples of children who achieved an ACR70 response to methotrexate at 6 months than in those who did not respond.
The difference was not initially significant, but a comparison of samples from children who achieved an ACR50 or an ACR70 response with those who had an ACR30 or no response did show a statistical benefit (P = .008).
“MRP8/14 is a very stable protein,” Dr. Moncrieffe said. It can be measured in a simple serum sample, left on a bench, and even sent through the post before being analyzed at a later date. It could therefore lend itself to the development of a routine predictive test and, together with the genetic findings from SPARKS-CHARMS, help physicians make clinical decisions based on a child's likelihood of responding to treatment.
Dr. Lucy Wedderburn, professor of pediatric rheumatology at UCL Institute of Child Health and an honorary consultant in rheumatology at Great Ormond Street Hospital, said, “MRP8/14 is a protein we already knew to be important.”
Dr. Wedderburn, lead investigator of the study, added: “Levels of this protein are very high in the serum of children with JIA and in those who respond well to treatment. Higher levels have also been found in children who are in remission when compared to children without JIA.”
The study was funded by SPARKS UK, The Big Lottery Fund, Arthritis Research UK, and Great Ormond Street Hospital Children's Charity. Dr. Moncrieffe and Dr. Wedderburn declared that they had no conflicts of interest.
Giving methotrexate to all children at diagnosis possibly represents a missed opportunity.
Source DR. MONCRIEFFE