Clinical and associated inflammatory biomarker features predictive of short-term outcomes in non-systemic juvenile idiopathic arthritis

Rheumatology (Oxford). 2020 Sep 1;59(9):2402-2411. doi: 10.1093/rheumatology/kez615.

Abstract

Objective: To identify early predictors of disease activity at 18 months in JIA using clinical and biomarker profiling.

Methods: Clinical and biomarker data were collected at JIA diagnosis in a prospective longitudinal inception cohort of 82 children with non-systemic JIA, and their ability to predict an active joint count of 0, a physician global assessment of disease activity of ≤1 cm, and inactive disease by Wallace 2004 criteria 18 months later was assessed. Correlation-based feature selection and ReliefF were used to shortlist predictors and random forest models were trained to predict outcomes.

Results: From the original 112 features, 13 effectively predicted 18-month outcomes. They included age, number of active/effused joints, wrist, ankle and/or knee involvement, ESR, ANA positivity and plasma levels of five inflammatory biomarkers (IL-10, IL-17, IL-12p70, soluble low-density lipoprotein receptor-related protein 1 and vitamin D), at enrolment. The clinical plus biomarker panel predicted active joint count = 0, physician global assessment ≤ 1, and inactive disease after 18 months with 0.79, 0.80 and 0.83 accuracy and 0.84, 0.83, 0.88 area under the curve, respectively. Using clinical features alone resulted in 0.75, 0.72 and 0.80 accuracy, and area under the curve values of 0.81, 0.78 and 0.83, respectively.

Conclusion: A panel of five plasma biomarkers combined with clinical features at the time of diagnosis more accurately predicted short-term disease activity in JIA than clinical characteristics alone. If validated in external cohorts, such a panel may guide more rationally conceived, biologically based, personalized treatment strategies in early JIA.

Keywords: JIA; arthritis; childhood arthritis; classification; cytokines; machine learning; predictors.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Ankle Joint / pathology
  • Area Under Curve
  • Arthritis, Juvenile / blood
  • Arthritis, Juvenile / diagnosis*
  • Arthritis, Juvenile / pathology
  • Biomarkers / blood
  • Canada
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Interleukin-10 / blood
  • Interleukin-12 / blood
  • Interleukin-17 / blood
  • Interleukins / blood*
  • Knee Joint / pathology
  • Longitudinal Studies
  • Low Density Lipoprotein Receptor-Related Protein-1 / blood*
  • Male
  • Predictive Value of Tests
  • Prospective Studies
  • Severity of Illness Index*
  • Vitamin D / blood*
  • Wrist Joint / pathology

Substances

  • Biomarkers
  • IL10 protein, human
  • Interleukin-17
  • Interleukins
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Interleukin-10
  • Vitamin D
  • Interleukin-12

Grants and funding