Methotrexate for maintaining remission in paediatric Crohn's patients with prior failure or intolerance to thiopurines: a multicenter cohort study

J Crohns Colitis. 2015 Apr;9(4):305-11. doi: 10.1093/ecco-jcc/jjv031. Epub 2015 Feb 5.

Abstract

Background and aims: Methotrexate [MTX] is an immunomodulating drug that can be used to maintain remission in patients with Crohn's disease [CD], but data on efficacy and tolerability in children and teenagers are scarce. We evaluated the long-term efficacy and tolerability of MTX monotherapy after thiopurine therapy in paediatric CD patients.

Methods: A multicenter cohort of paediatric MTX users who stopped thiopurines due to ineffectiveness or intolerance between 2002 and 2012 were included and followed for at least 12 months. Relapse-free use was defined as steroid and biologics-free clinical remission after the introduction of MTX, and included intentional discontinuation of successful therapy before the end of the observation period.

Results: A total of 113 patients with CD in remission were followed while on MTX monotherapy, of whom 75 [66%] had failed on thiopurines and 38 [34%] had stopped thiopurines due to side effects. Median age at the introduction of MTX was 14 years [range 7 to 17], and 93% used the subcutaneous route. Kaplan-Meier analysis showed that 52% of the study cohort were still in steroid- and biologics-free remission after 12 months of MTX monotherapy, with a difference that did not reach significance between thiopurine-intolerant and thiopurine-failing patients [p = 0.21, log-rank test].

Conclusions: The findings of this cohort study suggest that MTX is an effective immunomodulator to maintain remission after stopping thiopurines. MTX maintenance should be considered before stepping up to anti-tumor necrosis factor alpha therapy. MTX is probably somewhat more effective in patients who stopped thiopurines due to side effects than in those who failed on thiopurines.

Keywords: Crohn’s disease; methotrexate; immunomodulation; inflammatory bowel disease; thiopurine.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Crohn Disease / drug therapy*
  • Dose-Response Relationship, Drug
  • Drug Tolerance*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Injections, Subcutaneous
  • Male
  • Methotrexate / administration & dosage*
  • Methyltransferases / pharmacology
  • Remission Induction
  • Retrospective Studies
  • Treatment Failure
  • Treatment Outcome

Substances

  • Immunosuppressive Agents
  • Methyltransferases
  • thiopurine methyltransferase
  • Methotrexate