Efficacy of oral methotrexate in paediatric Crohn's disease

A multicentre propensity score study

Dan Turner, Etti Doveh, Ayala Cohen, Michelle L. Wilson, Andrew B. Grossman, Joel Rosh, Ying Lu, Athos Bousvaros, Colette Deslandres, Angela Noble, Robert N. Baldassano, Arie Levine, Aaron Lerner, David C. Wilson, Anne M. Griffiths

Research output: Contribution to journalArticle

23 Citations (Scopus)

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-byindication 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 Zchildren in complete remission treated with subcutaneous MTX to the oral route with close monitoring of inflammatory markers and growth.

Original languageEnglish (US)
Pages (from-to)1898-1904
Number of pages7
JournalGut
Volume64
Issue number12
DOIs
StatePublished - Dec 1 2015

Fingerprint

Propensity Score
Methotrexate
Crohn Disease
Nausea
Oral Administration
Cohort Studies
Steroids
Quality of Life
Pediatric Crohn's disease
Safety
Costs and Cost Analysis
Injections
Liver
Enzymes
Therapeutics
Growth

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Cite this

Turner, D., Doveh, E., Cohen, A., Wilson, M. L., Grossman, A. B., Rosh, J., ... Griffiths, A. M. (2015). Efficacy of oral methotrexate in paediatric Crohn's disease: A multicentre propensity score study. Gut, 64(12), 1898-1904. https://doi.org/10.1136/gutjnl-2014-307964
Turner, Dan ; Doveh, Etti ; Cohen, Ayala ; Wilson, Michelle L. ; Grossman, Andrew B. ; Rosh, Joel ; Lu, Ying ; Bousvaros, Athos ; Deslandres, Colette ; Noble, Angela ; Baldassano, Robert N. ; Levine, Arie ; Lerner, Aaron ; Wilson, David C. ; Griffiths, Anne M. / Efficacy of oral methotrexate in paediatric Crohn's disease : A multicentre propensity score study. In: Gut. 2015 ; Vol. 64, No. 12. pp. 1898-1904.
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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-byindication 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 Zchildren in complete remission treated with subcutaneous MTX to the oral route with close monitoring of inflammatory markers and growth.",
author = "Dan Turner and Etti Doveh and Ayala Cohen and Wilson, {Michelle L.} and Grossman, {Andrew B.} and Joel Rosh and Ying Lu and Athos Bousvaros and Colette Deslandres and Angela Noble and Baldassano, {Robert N.} and Arie Levine and Aaron Lerner and Wilson, {David C.} and Griffiths, {Anne M.}",
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Turner, D, Doveh, E, Cohen, A, Wilson, ML, Grossman, AB, Rosh, J, Lu, Y, Bousvaros, A, Deslandres, C, Noble, A, Baldassano, RN, Levine, A, Lerner, A, Wilson, DC & Griffiths, AM 2015, 'Efficacy of oral methotrexate in paediatric Crohn's disease: A multicentre propensity score study', Gut, vol. 64, no. 12, pp. 1898-1904. https://doi.org/10.1136/gutjnl-2014-307964

Efficacy of oral methotrexate in paediatric Crohn's disease : A multicentre propensity score study. / Turner, Dan; Doveh, Etti; Cohen, Ayala; Wilson, Michelle L.; Grossman, Andrew B.; Rosh, Joel; Lu, Ying; Bousvaros, Athos; Deslandres, Colette; Noble, Angela; Baldassano, Robert N.; Levine, Arie; Lerner, Aaron; Wilson, David C.; Griffiths, Anne M.

In: Gut, Vol. 64, No. 12, 01.12.2015, p. 1898-1904.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Efficacy of oral methotrexate in paediatric Crohn's disease

T2 - A multicentre propensity score study

AU - Turner, Dan

AU - Doveh, Etti

AU - Cohen, Ayala

AU - Wilson, Michelle L.

AU - Grossman, Andrew B.

AU - Rosh, Joel

AU - Lu, Ying

AU - Bousvaros, Athos

AU - Deslandres, Colette

AU - Noble, Angela

AU - Baldassano, Robert N.

AU - Levine, Arie

AU - Lerner, Aaron

AU - Wilson, David C.

AU - Griffiths, Anne M.

PY - 2015/12/1

Y1 - 2015/12/1

N2 - 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-byindication 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 Zchildren in complete remission treated with subcutaneous MTX to the oral route with close monitoring of inflammatory markers and growth.

AB - 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-byindication 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 Zchildren in complete remission treated with subcutaneous MTX to the oral route with close monitoring of inflammatory markers and growth.

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U2 - 10.1136/gutjnl-2014-307964

DO - 10.1136/gutjnl-2014-307964

M3 - Article

VL - 64

SP - 1898

EP - 1904

JO - Gut

JF - Gut

SN - 0017-5749

IS - 12

ER -