title: A subgroup of juvenile idiopathic arthritis patients who respond well to methotrexate are identified by the serum biomarker MRP8/14 protein.
abstract: OBJECTIVE
  In JIA there is an unmet need for biomarkers with which to identify patients who will respond well to MTX. The aim of this study was to define the prognostic value of baseline serum proteins and clinical variables in response to MTX to help inform the clinician at time of diagnosis whether the patient is likely to respond well to MTX.
  
  
  METHODS
  JIA patients were recruited into the Childhood Arthritis Response to Medication Study (CHARMS). Clinical data and venous blood were collected before administration of MTX and at follow-up. MRP8/14 and inflammatory cytokines were measured by ELISA and multiplex immunoassay, respectively. CRP and ESR were measured as part of routine clinical assessment. To explore which baseline factors might predict successful treatment, binary logistic regression models were fitted for outcome.
  
  
  RESULTS
  High disease activity (high serum MRP8/14, active joint count or physician's score) pre-MTX was observed in a subgroup of patients with a better response to therapy. In a multivariable analysis, after accounting for MRP8/14 at baseline, no other factors were independently significantly associated with outcome. Patients with baseline MRP8/14 >3000 ng/ml were more likely to respond to MTX at ACR50 or better: odds ratio 16.07 (95% CI 2.00, 129.3).
  
  
  CONCLUSIONS
  We have demonstrated that high levels of baseline serum MRP8/14 have prognostic value in predicting a subgroup of patients whose arthritis will improve on MTX. Routine collection of serum prior to the start of medication would be a valuable step in collaborative validation of such biomarkers.
authors.affiliation: Rheumatology Unit, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK. h.moncrieffe@ucl.ac.uk
authors.forename: Halima
authors.initials: H
authors.lastname: Moncrieffe
authors.forename: Simona
authors.initials: S
authors.lastname: Ursu
authors.forename: Dirk
authors.initials: D
authors.lastname: Holzinger
authors.forename: Fiona
authors.initials: F
authors.lastname: Patrick
authors.forename: Laura
authors.initials: L
authors.lastname: Kassoumeri
authors.forename: Angie
authors.initials: A
authors.lastname: Wade
authors.forename: Johannes
authors.initials: J
authors.lastname: Roth
authors.forename: Lucy R
authors.initials: LR
authors.lastname: Wedderburn
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000704:Analysis of Variance; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001171:Arthritis, Juvenile / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000378:metabolism; D040501:Calgranulin A / Q000097:blood*; D002648:Child; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016015:Logistic Models; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D040501:Calgranulin A; D002097:C-Reactive Protein; D008727:Methotrexate
keywords: CHARM study; biomarker; disease outcome; juvenile idiopathic arthritis; methotrexate; paediatric; response to treatment; rheumatology