Clinical outcome and pharmacokinetics after addition of low-dose cyclosporine to methotrexate: A case study of five patients with treatment-resistantinflammatory bowel disease

Introduction: This study reports the clinical outcome, toxicity, and methot rexate pharmacokinetics after the addition of low-dose cyclosporine to meth otrexate in patients with ulcerative colitis or Crohn's disease. Methods: T hree patients with steroid-refractory ulcerative colitis and two patients w ith steroid refractory Crohn's disease who failed monotherapy with subcutan eous 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 additi onal 16 weeks. Clinical response was measured with the Inflammatory Bowel D isease Questionnaire (IBDQ) score. Concentrations of erythrocyte methotrexa te, plasma methotrexate, and plasma 7-hydroxymethotrexate were also determi ned. Results: Both patients with Crohn's disease withdrew from the study fo r toxicity (headaches, seizure). The three patients with ulcerative colitis experienced clinical improvement with a mean increase in the IBDQ score fr om 164 to 190 points, p = 0.01. The mean serum creatinine in the three pati ents 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 metho trexate, 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 cyclo sporine-associated toxicity.