A single-center experience with methotrexate after thiopurine therapy in pediatric Crohn disease.
OBJECTIVE
Thiopurines are a common, effective means of maintaining remission in pediatric Crohn disease (CD). Methotrexate (MTX) may be considered for those intolerant of or unresponsive to thiopurines. The purpose of this study was to examine the effectiveness of MTX as maintenance therapy in patients previously treated with thiopurines.


METHODS
All of the patients at Nationwide Children's Hospital from 1998 to 2007 with an International Classification of Diseases code indicative of CD were identified. Patients with a diagnosis of CD, a history of prior thiopurine use, no current infliximab therapy, and at least 6 months of follow-up after MTX initiation were included. The primary outcome was defined as steroid-/infliximab-free remission determined by the physician global assessment at 6 and 12 months. Secondary outcomes included subsequent treatment with infliximab and/or corticosteroids, rate of discontinuation of MTX, and adverse events (AEs).


RESULTS
Twenty-seven patients (17 boys, 63%) with a mean age at diagnosis of 12.3 ± 0.7 years and mean disease duration of 1.49 ± 0.3 years were identified. Indications for MTX included nonresponse to thiopurines, AE, and poor adherence to thiopurines. At 6 and 12 months, 13 of 27 patients (48.1%) and 9 of 27 patients (33.3%), respectively, were in steroid-/infliximab-free remission. A total of 10 patients (37.0%) required infliximab therapy during the 12-month period and 5 patients discontinued MTX. Nausea was the most commonly reported AE. Transient transaminase elevation occurred in 4 patients and transient leukopenia in 2 patients.


CONCLUSIONS
MTX can be effective as maintenance therapy for patients with pediatric CD previously intolerant of or unresponsive to thiopurines; however, greater than one third of this cohort required escalation to antitumor necrosis factor therapy within 12 months following MTX initiation. MTX was well tolerated.
Boyle
Brendan
B
Department of Pediatrics, Division of Pediatric Gastroenterology, Nationwide Children's Hospital, Columbus, OH, USA. brendan.boyle@nationwidechildrens.org
Mackner
Laura
L
Ross
Christina
C
Moses
Jonathan
J
Kumar
Soma
S
Crandall
Wallace
W
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002648:Child; D003424:Crohn Disease / Q000188:drug therapy*; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D000069285:Infliximab; D007970:Leukopenia / Q000209:etiology; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects / Q000627:therapeutic use*; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D008780:Methyltransferases / Q000627:therapeutic use; D009325:Nausea / Q000139:chemically induced; D017063:Outcome Assessment, Health Care; D010349:Patient Compliance; D012074:Remission Induction; D012189:Retrospective Studies; D000637:Transaminases / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000069285:Infliximab; D015122:Mercaptopurine; D008780:Methyltransferases; D000637:Transaminases; D008727:Methotrexate