Issue 05

Clinical Question

Does the delivery method of methotrexate (MTX) impact its effectiveness or toxicity in paediatric Crohn’s disease (CD)?

Editor’s Bottom Line

Subcutaneous MTX is marginally superior to oral MTX in pediatric CD, but only in some outcomes.

Editorial Note

It is reasonable to consider switching children in complete remission on MTX from a subcutaneous delivery to an oral delivery route.

Reference

Turner D, Doveh E, Cohen A, et al. Efficacy of oral methotrexate in paediatric Crohn’s disease: a multicentre propensity score study. Gut. 2015 Dec;64(12):1898–904. https://www.ncbi.nlm.nih.gov/pubmed/25416066

Synopsis

In this retrospective, multicentre review, eligible children with CD were included if they had received MTX orally (PO), subcutaneously (SC), or switched from subcutaneous to oral within the first year of treatment (SC/PO). All were naïve to biologics but could have received thiopurines previously. Medical chart reviews were conducted and the children followed for 1 year. The study’s primary endpoint was sustained steroid-free remission (PCDAI ≤10), as well as no fistula drainage, at 1 year with continuous MTX and no need for treatment escalation (e.g., steroids, biologics, or surgery). Secondary endpoints included growth rate, dose escalation, adverse events, time to remission, and steroid use. Differences between the cohorts were accounted for by the propensity score method.

A total of 226 children were enrolled (PO=38; SC=90; SC/PO=98) and had a mean age of 13.8 years. 88% had previously taken thiopurines. At 1 year, 76 children (34%) achieved sustained steroid-free remission with no significant difference between the PO and SC cohorts while the SC/PO cohort was superior to both PO and SC (P≤0.004 for each). Height velocity measured 1 year after starting MTX was significantly lower in the PO group relative to the SC or SC/PO groups (P≤0.006 for each). No differences were found between the groups for treatment escalation. Adverse events were highest for the SC/PO group relative to the SC and PO groups. Those in the PO group had the longest time to remission.

Details

Study Design: Retrospective cohort study
Funding: Medical Research Council and GI-Nutrition research fund
Allocation: n/a
Setting: Multiple centres from North America, Europe, and Israel
Level of Evidence: 2b (Oxford Levels of Evidence)

The summary and conclusion in this issue of E-mentoring in IBD pertains to the manuscript(s) being reviewed, and should be considered in the context of what is already known surrounding the topic and incorporated into practice as deemed appropriate by the individual learner.