title: Methotrexate intolerance in oral and subcutaneous administration in patients with juvenile idiopathic arthritis: a cross-sectional, observational study.
abstract: OBJECTIVE
  Methotrexate (MTX) is the cornerstone disease-modifying anti-rheumatic drug (DMARD) in juvenile idiopathic arthritis (JIA). In Dutch patients, MTX intolerance occurred frequently and was associated with subcutaneous (SC) administration. The aim of this study was to assess the prevalence of MTX intolerance and its association with the route of administration in a German cohort of JIA patients.
  
  
  METHODS
  A cross-sectional study of JIA patients on MTX was performed. Primary outcome was MTX intolerance, which was determined using the validated Methotrexate Intolerance Severity Score (MISS) questionnaire. The prevalence of gastrointestinal adverse effects and MTX intolerance was compared between patients on MTX SC and MTX administered orally (PO).
  
  
  RESULTS
  Of 179 JIA patients on MTX, 73 (40.8%) were intolerant. The odds of MTX intolerance were higher in patients using MTX exclusively SC compared to exclusively PO (adjusted odds ratio 3.37 [95% confidence interval 1.19-10.0]). There was strong evidence that the former experienced more behavioural complaints (76.1% vs. 47.4%, p=0.001) and weak evidence that they experienced more abdominal pain after MTX intake (43.5% vs. 27.4%, p=0.056).
  
  
  CONCLUSIONS
  The prevalence of MTX intolerance was high and exclusively SC administration of MTX was associated with MTX intolerance and behavioural adverse effects. The prevalence of gastrointestinal adverse effects was at least as high as in patients on MTX PO. The frequently held assumption that SC causes fewer side effects than PO seems unwarranted. Definite answers about the differences between SC and PO administration with respect to safety and efficacy should be obtained by randomised trials.
authors: University Medical Center Utrecht, The Netherlands; and IRCCS G. Gaslini, Genoa, Italy. e.h.p.dijkhuizen@umcutrecht.nl.
authors: E H Pieter
authors: EH
authors: van Dijkhuizen
authors: University Medical Center Utrecht, The Netherlands.
authors: Juliëtte N
authors: JN
authors: Pouw
authors: German Center for Paediatric and Adolescent Rheumatology, Garmisch-Partenkirchen, Germany.
authors: Andrea
authors: A
authors: Scheuern
authors: German Center for Paediatric and Adolescent Rheumatology, Garmisch-Partenkirchen, Germany.
authors: Boris
authors: B
authors: Hügle
authors: St. Josef-Stift, Sendenhorst, Germany.
authors: Sven
authors: S
authors: Hardt
authors: St. Josef-Stift, Sendenhorst, Germany.
authors: Gerd
authors: G
authors: Ganser
authors: University Hospital Tübingen, Germany.
authors: Jasmin Beate
authors: JB
authors: Kümmerle-Deschner
authors: Asklepios Klinik Sankt Augustin, Sankt Augustin, Germany.
authors: Gerd
authors: G
authors: Horneff
authors: University Children's Hospital Münster, Germany.
authors: Dirk
authors: D
authors: Holzinger
authors: University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Maja
authors: M
authors: Bulatović Ćalasan
authors: University Medical Center Utrecht, The Netherlands.
authors: Nico M
authors: NM
authors: Wulffraat
mesh_terms: D015746:Abdominal Pain / Q000139:chemically induced / Q000453:epidemiology; D000284:Administration, Oral; D000293:Adolescent; D000294:Adolescent Behavior / Q000187:drug effects; D000367:Age Factors; D001171:Arthritis, Juvenile / Q000175:diagnosis / Q000188:drug therapy*; D016009:Chi-Square Distribution; D002648:Child; D002652:Child Behavior / Q000187:drug effects; D003430:Cross-Sectional Studies; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D007279:Injections, Subcutaneous; D016015:Logistic Models; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects*; D015999:Multivariate Analysis; D009325:Nausea / Q000139:chemically induced / Q000453:epidemiology; D016017:Odds Ratio; D015995:Prevalence; D012307:Risk Factors; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced / Q000453:epidemiology
chemical_list: D007166:Immunosuppressive Agents; D008727:Methotrexate