title: High prevalence of methotrexate intolerance in juvenile idiopathic arthritis: development and validation of a methotrexate intolerance severity score.
abstract: OBJECTIVE
  To design and validate a new questionnaire for identifying patients with methotrexate (MTX) intolerance, and to determine the prevalence of MTX intolerance in patients with juvenile idiopathic arthritis (JIA) using this questionnaire.
  
  
  METHODS
  The MTX Intolerance Severity Score (MISS) questionnaire was constructed, consisting of 5 domains: stomach ache, nausea, vomiting, sore mouth, and behavioral symptoms. The domains each consisted of 3 questions pertaining to the presence of a symptom upon, prior to (anticipatory), and when thinking of (associative) MTX intake. The MISS questionnaire was validated in 86 patients by determining its discriminative power between patients with and those without MTX intolerance, identified as such by a gold standard (physician's opinion). Using the MISS questionnaire, the prevalence of MTX intolerance was determined in 297 JIA patients.
  
  
  RESULTS
  The MISS questionnaire discriminated well between MTX-intolerant and MTX-tolerant patients. A cutoff score of 6 yielded the best sensitivity (88%) and specificity (80%). MTX intolerance was found in 150 (50.5%) of 297 patients. Of 220 patients receiving oral MTX, 98 (44.5%) experienced MTX intolerance, whereas 67.5% of 77 patients receiving parenteral MTX experienced intolerance to the drug (P = 0.001).
  
  
  CONCLUSIONS
  Our findings indicate that the MISS questionnaire is a highly sensitive and specific tool for the diagnosis of MTX intolerance, and that there is a high prevalence of MTX intolerance among JIA patients. The prevalence of intolerance in patients receiving parenteral MTX exceeds that in patients receiving oral MTX. The frequent occurrence of anticipatory and associative symptoms suggests that classic conditioning plays an important role in MTX intolerance.
authors: University Medical Centre Utrecht, Utrecht, The Netherlands.
authors: Maja
authors: M
authors: Bulatović
authors: Marloes W
authors: MW
authors: Heijstek
authors: Marleen
authors: M
authors: Verkaaik
authors: E H Pieter
authors: EH
authors: van Dijkhuizen
authors: Wineke
authors: W
authors: Armbrust
authors: Esther P A
authors: EP
authors: Hoppenreijs
authors: Sylvia
authors: S
authors: Kamphuis
authors: Wietse
authors: W
authors: Kuis
authors: Toine C G
authors: TC
authors: Egberts
authors: Gerben
authors: G
authors: Sinnema
authors: Carin M A
authors: CM
authors: Rademaker
authors: Nico M
authors: NM
authors: Wulffraat
mesh_terms: D000293:Adolescent; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001171:Arthritis, Juvenile / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis* / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000009:adverse effects* / Q000627:therapeutic use; D012372:ROC Curve; D012680:Sensitivity and Specificity; D011795:Surveys and Questionnaires
chemical_list: D018501:Antirheumatic Agents; D008727:Methotrexate