Use of methotrexate in refractory Crohn's disease: the Edinburgh experience.
BACKGROUND
In the two benchmark controlled trials in Crohn's disease (CD) supporting its use, methotrexate (MTX) was used as the immunosuppressant of choice in immunomodulatory-naive patients. However, in daily clinical practice MTX is used generally after thiopurine analogs have failed.


METHODS
The data are reported using intramuscular (IM) MTX (25 mg/week) in the induction of remission and oral MTX (15 mg/week) in 39 CD patients with a median age of 32 years, assessed retrospectively. In all, 97% patients had failed azathioprine and/or mercaptopurine therapy due to lack of efficacy in 14 (36%) and side effects in 24 (61%) patients; 21 patients (53%) were steroid-dependent with a median dose of 27.5 mg prednisolone/day for over a year.


RESULTS
In all, 72% of patients tolerated an induction regimen of 25 mg/week of IM MTX; 10% managed a reduced dose and 18% were intolerant. Remission was achieved in 71% of patients at 16 weeks. In the patients taking corticosteroids, withdrawal was achieved in 26% of patients and reduction in 47% at 16 weeks. Oral MTX therapy was continued in 22 patients after induction. In this group the probability of relapse was 78% at 50 weeks of oral therapy.


CONCLUSIONS
Parenteral MTX therapy is efficacious in inducing remission in steroid-dependent CD patients, although its use is limited by side effects in approximately 30% of patients. Low-dose oral therapy does not maintain long-term remission and is not a suitable alternative.
Din
Shahida
S
Gastrointestinal Unit, Molecular Medicine Centre, University of Edinburgh, Edinburgh, UK. Shhddn@aol.com
Dahele
Anna
A
Fennel
Janice
J
Aitken
Sue
S
Shand
Alan G
AG
Arnott
Ian D R
ID
Satsangi
Jack
J
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001379:Azathioprine / Q000008:administration & dosage; D003424:Crohn Disease / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000069285:Infliximab; D007273:Injections, Intramuscular; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use*; D011239:Prednisolone / Q000627:therapeutic use; D012074:Remission Induction; D012189:Retrospective Studies
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D011239:Prednisolone; D000069285:Infliximab; D001379:Azathioprine; D008727:Methotrexate