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Prediction of methotrexate intolerance in juvenile idiopathic arthritis: a prospective, observational cohort study

Evert Hendrik Pieter van Dijkhuizen1, Maja Bulatović Ćalasan2, Saskia M F Pluijm3

  • 1Department of Paediatric Immunology, University Medical Centre Utrecht, Wilhelmina Children's Hospital, Utrecht, The Netherlands ; Pediatria II, Reumatologia, IRCCS G. Gaslini, Largo Gaslini 5, 16147 Genova, Italy.

Pediatric Rheumatology Online Journal
|March 7, 2015
PubMed
Abstract

Insights

A new risk model can predict methotrexate intolerance in juvenile idiopathic arthritis patients, aiding early intervention. This tool helps identify individuals at risk, improving treatment adherence and outcomes.

Area of Science:

  • Pediatric Rheumatology
  • Pharmacogenomics

Background:

  • Methotrexate (MTX) is a key treatment for juvenile idiopathic arthritis (JIA).
  • MTX intolerance, characterized by gastrointestinal adverse effects, frequently leads to poor treatment adherence.
  • Predicting MTX intolerance is crucial for optimizing JIA management.

Purpose of the Study:

  • To develop and validate a clinical prediction model for MTX intolerance in JIA patients.
  • To identify key predictors of MTX intolerance for early risk assessment.

Main Methods:

  • A prospective JIA cohort study involving 152 patients.
  • Clinical variables and single nucleotide polymorphisms were assessed at MTX initiation.
  • Multivariable logistic regression and bootstrapping were used for model development and internal validation.

Main Results:

  • The prediction model incorporated JIA category, antinuclear antibody status, pain assessment, disease activity score, thrombocytes, alanine aminotransferase, and creatinine.
  • The model achieved 77.5% accuracy upon initial development and 66.7% after internal validation.
  • A risk score (0-17) was developed, with a cut-off of ≥6 showing 82.0% sensitivity and 56.1% specificity for MTX intolerance.

Conclusions:

  • The developed clinical prediction model demonstrates moderate ability to identify patients at risk of MTX intolerance.
  • Further validation in independent cohorts and inclusion of additional predictors are necessary for clinical utility.
  • This tool could enable timely interventions to prevent MTX intolerance and improve JIA patient outcomes.
Keywords:
Adverse eventsJuvenile idiopathic arthritisMethotrexateMethotrexate intolerancePrediction modelPredictor

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