A randomized dose-response and pharmacokinetic study of methotrexate for refractory inflammatory Crohn's disease and ulcerative colitis.
OBJECTIVE
The optimum initial dose of methotrexate for steroid-requiring inflammatory bowel disease is not known.


OBJECTIVE
To compare directly the efficacy and toxicity of methotrexate 15 and 25 mg/week, and to explore the value of methotrexate blood levels as predictors of outcome.


METHODS
A 16-week randomized single-blind comparison of subcutaneous methotrexate 15 or 25 mg/week was performed in 32 patients with steroid-requiring Crohn's disease or ulcerative colitis. Patients who did not respond to methotrexate 15 mg/week were further studied for an additional 16 weeks on methotrexate 25 mg/week. Blood was drawn every 2 weeks for methotrexate levels.


RESULTS
After 16 weeks, 17% of patients in each group achieved remission; 39% of patients randomized to 15 mg/week and 33% of patients randomized to 25 mg/week improved (P=N.S. ). Clinical status improved in four out of 11 patients after methotrexate dose escalation from 15 to 25 mg/week. Toxicity was not different between the treatment groups. Methotrexate blood levels did not predict efficacy or toxicity.


CONCLUSIONS
For induction of remission in steroid-requiring inflammatory bowel disease, subcutaneous methotrexate at initial doses of 15 and 25 mg/week are equally efficacious. At these doses, response is not associated with blood methotrexate concentrations.
Egan
L J
LJ
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.
Sandborn
W J
WJ
Tremaine
W J
WJ
Leighton
J A
JA
Mays
D C
DC
Pike
M G
MG
Zinsmeister
A R
AR
Lipsky
J J
JJ
D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D003424:Crohn Disease / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D008727:Methotrexate / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use*; D008875:Middle Aged; D016037:Single-Blind Method; D013997:Time Factors; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D008727:Methotrexate