A subgroup of juvenile idiopathic arthritis patients who respond well to methotrexate are identified by the serum biomarker MRP8/14 protein

Rheumatology (Oxford). 2013 Aug;52(8):1467-76. doi: 10.1093/rheumatology/ket152. Epub 2013 Apr 25.


Objectives: 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).

Conclusion: 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.

Keywords: CHARM study; biomarker; disease outcome; juvenile idiopathic arthritis; methotrexate; paediatric; response to treatment; rheumatology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Analysis of Variance
  • Antirheumatic Agents / administration & dosage*
  • Arthritis, Juvenile / blood*
  • Arthritis, Juvenile / diagnosis
  • Arthritis, Juvenile / drug therapy*
  • Biomarkers / blood
  • Blood Sedimentation
  • C-Reactive Protein / metabolism
  • Calgranulin A / blood*
  • Child
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Humans
  • Logistic Models
  • Male
  • Methotrexate / administration & dosage*
  • Predictive Value of Tests
  • Risk Assessment
  • Severity of Illness Index
  • Treatment Outcome
  • Young Adult


  • Antirheumatic Agents
  • Biomarkers
  • Calgranulin A
  • C-Reactive Protein
  • Methotrexate