Dan Turner1, Etti Doveh2, Ayala Cohen2, Michelle L Wilson3, Andrew B Grossman4, Joel R Rosh5, Ying Lu6, Athos Bousvaros6, Colette Deslandres7, Angela Noble7, Robert N Baldassano4, Arie Levine8, Aaron Lerner9, David C Wilson3, Anne M Griffiths10. 1. The Juliet Keidan Institute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel. 2. The Technion Institute of Technology, Haifa, Israel. 3. Department of Child Life and Health, University of Edinburgh, Scotland, UK. 4. Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, USA. 5. Goryeb Children's Hospital/Atlantic Health, Icahn School of Medicine at Mount Sinai, USA. 6. Division of Gastroenterology, Hepatology & Nutrition, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts. 7. Gastroenterology, Hepatology and Nutrition Service, CHU Sainte-Justine and Research Center, Montreal, Quebec. 8. Pediatric Gastroenterology Unit, Wolfson Medical Center, Tel Aviv University, Holon, Israel. 9. Pediatric Gastroenterology and Nutrition Unit, Carmel Medical Center, Technion-Israel Institute of Technology, Haifa, Israel. 10. Division of GI/Hepatology/Nutrition, SickKids Hospital, University of Toronto, Toronto, Ontario, Canada.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
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Authors: Neera Gupta; Robert H Lustig; Howard Andrews; Ranjana Gokhale; Alka Goyal; Ashish S Patel; Stephen Guthery; Francisco Sylvester; Leah Siebold; Cheng-Shiun Leu Journal: Inflamm Bowel Dis Date: 2021-05-17 Impact factor: 7.290