title: Methotrexate for maintaining remission in paediatric Crohn's patients with prior failure or intolerance to thiopurines: a multicenter cohort study.
abstract: OBJECTIVE
  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.
authors: University of Groningen, University Medical Center Groningen, Department of Pediatric Gastroenterology, Groningen, The Netherlands.
authors: Sjoukje-Marije
authors: SM
authors: Haisma
authors: University of Groningen, University Medical Center Groningen, Department of Pediatric Gastroenterology, Groningen, The Netherlands.
authors: Thijs
authors: T
authors: Lijftogt
authors: Emma's Children's Hospital, University of Amsterdam, Amsterdam, The Netherlands.
authors: Angelika
authors: A
authors: Kindermann
authors: Department of Pediatrics, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands.
authors: Gerard
authors: G
authors: Damen
authors: Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors: Lissy
authors: L
authors: de Ridder
authors: Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors: Johanna C
authors: JC
authors: Escher
authors: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors: M Luisa
authors: ML
authors: Mearin
authors: VU University Medical Center Amsterdam, Amsterdam, The Netherlands.
authors: Tim
authors: T
authors: de Meij
authors: Juliana Children's Hospital/Haga Teaching Hospital, The Hague, The Netherlands.
authors: Daniëlle
authors: D
authors: Hendriks
authors: Medisch Centrum Alkmaar, Alkmaar, The Netherlands.
authors: Elvira
authors: E
authors: George
authors: Medisch Spectrum Twente, Enschede, The Netherlands.
authors: Thalia
authors: T
authors: Hummel
authors: Isala, Princess Amalia Department of Pediatrics, Zwolle, The Netherlands.
authors: Obbe
authors: O
authors: Norbruis
authors: University of Groningen, University Medical Center Groningen, Department of Pediatric Gastroenterology, Groningen, The Netherlands p.f.van.rheenen@umcg.nl.
authors: Patrick
authors: P
authors: van Rheenen
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003424:Crohn Disease / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007279:Injections, Subcutaneous; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008780:Methyltransferases / Q000494:pharmacology; D012074:Remission Induction; D012189:Retrospective Studies; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D008727:Methotrexate
keywords: Crohn’s disease; methotrexate; immunomodulation; inflammatory bowel disease; thiopurine