title: Efficacy of oral methotrexate in paediatric Crohn's disease: a multicentre propensity score study.
abstract: BACKGROUND
  Oral methotrexate (MTX) administration avoids weekly injections, reduces costs and may improve quality of life of patients with Crohn's disease (CD), especially children. Routes of administration have never been systematically compared in CD. We aimed to compare effectiveness and safety of orally (PO) versus subcutaneously (SC) administered MTX in paediatric CD.
  
  
  METHODS
  226 children with CD treated with oral or subcutaneous MTX were included in a multicentre, retrospective 1-year cohort study (62% boys, mean age 13.8±2.8 years, 88% previous thiopurines). 38 (17%) were initially commenced on oral, 98 (43%) started subcutaneous and switched to oral and 90 (40%) were treated with subcutaneous only. Matching and 'doubly robust' weighted regression models were based on the propensity score method, controlling for confounding-by-indication bias. 11/23 pretreatment variables were different between the groups, but the propensity score modelling successfully balanced the treatment groups.
  
  
  RESULTS
  76 children (34%) had sustained steroid-free remission with a difference that did not reach significance between the PO and the SC groups (weighted OR=1.72 (95% CI 0.5 to 5.9); p=0.52). There were no differences in need for treatment escalation (p=0.24), elevated liver enzymes (p=0.59) or nausea (p=0.85). Height velocity was lower in the PO group (p=0.006) and time to remission was delayed in the PO group (p=0.036; Fleming (0, 1) test).
  
  
  CONCLUSIONS
  In this largest paediatric CD cohort to date, SC administered MTX was superior to PO, but only in some of the outcomes and with a modest effect size. Therefore, it may be reasonable to consider switching children in complete remission treated with subcutaneous MTX to the oral route with close monitoring of inflammatory markers and growth.
authors.affiliation: The Juliet Keidan Institute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Dan
authors.initials: D
authors.lastname: Turner
authors.affiliation: The Technion Institute of Technology, Haifa, Israel.
authors.forename: Etti
authors.initials: E
authors.lastname: Doveh
authors.affiliation: The Technion Institute of Technology, Haifa, Israel.
authors.forename: Ayala
authors.initials: A
authors.lastname: Cohen
authors.affiliation: Department of Child Life and Health, University of Edinburgh, Scotland, UK.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Wilson
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, USA.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Grossman
authors.affiliation: Goryeb Children's Hospital/Atlantic Health, Icahn School of Medicine at Mount Sinai, USA.
authors.forename: Joel R
authors.initials: JR
authors.lastname: Rosh
authors.affiliation: Division of Gastroenterology, Hepatology & Nutrition, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Division of Gastroenterology, Hepatology & Nutrition, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts.
authors.forename: Athos
authors.initials: A
authors.lastname: Bousvaros
authors.affiliation: Gastroenterology, Hepatology and Nutrition Service, CHU Sainte-Justine and Research Center, Montreal, Quebec.
authors.forename: Colette
authors.initials: C
authors.lastname: Deslandres
authors.affiliation: Gastroenterology, Hepatology and Nutrition Service, CHU Sainte-Justine and Research Center, Montreal, Quebec.
authors.forename: Angela
authors.initials: A
authors.lastname: Noble
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, USA.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Baldassano
authors.affiliation: Pediatric Gastroenterology Unit, Wolfson Medical Center, Tel Aviv University, Holon, Israel.
authors.forename: Arie
authors.initials: A
authors.lastname: Levine
authors.affiliation: Pediatric Gastroenterology and Nutrition Unit, Carmel Medical Center, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Aaron
authors.initials: A
authors.lastname: Lerner
authors.affiliation: Department of Child Life and Health, University of Edinburgh, Scotland, UK.
authors.forename: David C
authors.initials: DC
authors.lastname: Wilson
authors.affiliation: Division of GI/Hepatology/Nutrition, SickKids Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Griffiths
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D001827:Body Height / Q000187:drug effects; D002648:Child; D002657:Child Development / Q000187:drug effects; D002675:Child, Preschool; D003424:Crohn Disease / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007279:Injections, Subcutaneous; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D009325:Nausea / Q000139:chemically induced; D057216:Propensity Score; D012074:Remission Induction; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D008727:Methotrexate
keywords: IBD CLINICAL