R08 Real-life use of MRP8/14 serum level measurement in clinical practice as a predictor of outcome after stopping methotrexate in patients with juvenile idiopathic arthritis

Abstract

Background: Many patients with JIA who reach clinical remission on treatment harbour residual inflammation that is not detectable by standard measures. MTX remains the first line DMARD for JIA, but is frequently poorly tolerated due to gastrointestinal side effects. After stopping MTX there is a significant risk of disease flare. Myeloid related protein (MRP) 8/14 has been shown as a marker of subclinical disease activity and a predictor of patients with risk of disease flare after stopping MTX. This study reviewed the impact of measuring serum MRP8/14 concentration in clinical practice, to identify patients who have reduced risk of disease flare if they stop MTX therapy. Methods: MRP8/14 tests performed at a single paediatric centre using a commercially available assay (Bü hlmann) were analysed. Patients included all subtypes of JIA, treated by MTX monotherapy at time of test and had not previously been on a biologic or other diseasemodifying drug. All were considering stopping MTX. Clinically inactive disease (CID) was defined by Wallace criteria. JIA subtype, gender, age at diagnosis, disease duration, age at sample and disease activity variables were recorded at time of test and over time. Disease flare in those off MTX was defined as a patient that no longer met Wallace criteria and required new intervention. Patients who met the inclusion criteria were divided into those who did or did not meet Wallace criteria,and whether they stopped, weaned or did not stop MTX . Statistical analyses were performed using Prism Graphpad, Version 7. Results: A total of 72 serum MRP8/14 concentrations from 72 patients were analysed. In patients who met Wallace criteria, comparison of serum MRP8/14 concentration values in those who stopped versus those who didn't stop MTX, demonstrated statistically significant difference (Mann-Whitney test). In the group who stopped MTX (n=18), sensitivity (high MRP8/14 indicating flare) was 86%, specificity (low MRP8/14 indicating no flare) was 18% and the positive predictive value (percentage of patients with a high MRP8/14 result who went on to flare) was 40%. Flares in patients who met Wallace criteria and stopped MTX treatment were plotted over time, split by the MRP8/14 result; low (<4000ng/ml), n=6 and high (>4000ng/ml), n=1. Statistical analysis showed no significant difference between groups, likely due to small numbers in the analysis, however the trend matched previous data. Conclusion: Measurement of serum MRP8/14 can be used in clinical practice to assist therapy decisions and as a predictor of flare post stopping MTX therapy in JIA patients who have achieved CID. However, biomarkers providing greater predictive power are needed to enable more accurate tailoring of treatment.