Article Text

Download PDFPDF
Original article
Efficacy of oral methotrexate in paediatric Crohn’s disease: a multicentre propensity score study
  1. Dan Turner1,
  2. Etti Doveh2,
  3. Ayala Cohen2,
  4. Michelle L Wilson3,
  5. Andrew B Grossman4,
  6. Joel R Rosh5,
  7. Ying Lu6,
  8. Athos Bousvaros6,
  9. Colette Deslandres7,
  10. Angela Noble7,
  11. Robert N Baldassano4,
  12. Arie Levine8,
  13. Aaron Lerner9,
  14. David C Wilson3,
  15. Anne M Griffiths10
  1. 1The Juliet Keidan Institute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel
  2. 2The Technion Institute of Technology, Haifa, Israel
  3. 3Department of Child Life and Health, University of Edinburgh, Scotland, UK
  4. 4Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, USA
  5. 5Goryeb Children's Hospital/Atlantic Health, Icahn School of Medicine at Mount Sinai, USA
  6. 6Division of Gastroenterology, Hepatology & Nutrition, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts
  7. 7Gastroenterology, Hepatology and Nutrition Service, CHU Sainte-Justine and Research Center, Montreal, Quebec
  8. 8Pediatric Gastroenterology Unit, Wolfson Medical Center, Tel Aviv University, Holon, Israel
  9. 9Pediatric Gastroenterology and Nutrition Unit, Carmel Medical Center, Technion-Israel Institute of Technology, Haifa, Israel
  10. 10Division of GI/Hepatology/Nutrition, SickKids Hospital, University of Toronto, Toronto, Ontario, Canada
  1. Correspondence to Dr Dan Turner, The Juliet Keidan Institute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, The Hebrew University; P.O.B 3235, Jerusalem 91031, Israel; turnerd{at}


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.


Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.