Clinical outcome and pharmacokinetics after addition of low-dose cyclosporine to methotrexate: a case study of five patients with treatment-resistant inflammatory bowel disease.
BACKGROUND
This study reports the clinical outcome, toxicity, and methotrexate pharmacokinetics after the addition of low-dose cyclosporine to methotrexate in patients with ulcerative colitis or Crohn's disease.


METHODS
Three patients with steroid-refractory ulcerative colitis and two patients with steroid refractory Crohn's disease who failed monotherapy with subcutaneous methotrexate 25 mg/week for 16 weeks were treated with the combination of methotrexate and low-dose oral cyclosporine (3 mg/kg/day) for an additional 16 weeks. Clinical response was measured with the Inflammatory Bowel Disease Questionnaire (IBDQ) score. Concentrations of erythrocyte methotrexate, plasma methotrexate, and plasma 7-hydroxymethotrexate were also determined.


RESULTS
Both patients with Crohn's disease withdrew from the study for toxicity (headaches, seizure). The three patients with ulcerative colitis experienced clinical improvement with a mean increase in the IBDQ score from 164 to 190 points, p = 0.01. The mean serum creatinine in the three patients who completed the study increased from 0.9 mg/dL at baseline to 1.2 mg/dL at week 16. p = 0.04. One patient developed hypertension. There was no significant change from baseline in the concentrations of erythrocyte methotrexate, plasma methotrexate, and plasma 7-hydroxymethotrexate.


CONCLUSIONS
Combination therapy with methotrexate and low-dose oral cyclosporine did not alter methotrexate pharmacokinetics and resulted in high rates of cyclosporine-associated toxicity.
Egan
L J
LJ
Inflammatory Bowel Disease Clinic, Division of Gastroenterology and Hepatology, and Clinical Pharmacology Unit, Mayo Clinic, Rochester, Minnesota 55905, USA.
Tremaine
W J
WJ
Mays
D C
DC
Lipsky
J J
JJ
Sandborn
W J
WJ
D003093:Colitis, Ulcerative / Q000188:drug therapy*; D003424:Crohn Disease / Q000188:drug therapy*; D016572:Cyclosporine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008727:Methotrexate / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012008:Recurrence; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D008727:Methotrexate