Methotrexate following unsuccessful thiopurine therapy in pediatric Crohn's disease.
BACKGROUND
The thiopurines, azathioprine and 6-mercaptopurine, are traditional first-line immunomodulatory agents in adult and pediatric Crohn's disease, but the comparative efficacy and safety of methotrexate have seldom been examined. We report outcomes with methotrexate treatment in pediatric patients previously refractory to or intolerant of thiopurines.


METHODS
In a four-center, retrospective cohort study, efficacy of methotrexate in maintaining remission was assessed by PCDAI measurements, steroid use, and height velocity. Patients served as their own historical controls. Multivariable analysis controlled for route of methotrexate administration, reason for thiopurine discontinuation, baseline disease activity, and disease duration.


RESULTS
Forty-two percent of 60 children treated with methotrexate were in clinical remission without steroids at both 6 and 12 months. A strong steroid sparing effect was observed compared with the year prior to methotrexate (P<0.001). Success rates were similar in previously thiopurine-intolerant and refractory patients. Height velocity increased from -1.9 SDS to -0.14 SDS (P=0.004) in the year following therapy. In a median 3-yr follow-up, a third of the patients did not require escalation of therapy; the others required step-up therapy with infliximab or surgery. Eight children (13%) stopped methotrexate due to adverse events, including, most commonly, elevated liver enzymes, and one serious episode of sepsis.


CONCLUSIONS
Methotrexate appears effective in maintaining remission in pediatric Crohn's disease, when thiopurines have failed. Consideration should be given to its use earlier in pediatric treatment algorithms.
Division of Gastroenterology, Hepatology, and Nutrition, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
Dan
D
Turner
Andrew B
AB
Grossman
Joel
J
Rosh
Subra
S
Kugathasan
Ashley R
AR
Gilman
Robert
R
Baldassano
Anne M
AM
Griffiths
D000293:Adolescent; D016009:Chi-Square Distribution; D002648:Child; D003424:Crohn Disease / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D017211:Treatment Failure; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; C488629:azathiopurine; D015122:Mercaptopurine; D008727:Methotrexate