Objective: High-dose ( >5 mg/kg/d) oral cyclosporine may be effective treatment for Crohn's disease, whereas low-dose oral cyclosporine ( < or = 5 mg/kg/d) is not. This study determined the correlation between blood and intestinal tissue cyclosporine concentrations and clinical response in patients with Crohn's disease treated with cyclosporine 8 mg/kg/day.
Methods: Twelve patients with inflammatory Crohn's disease were treated for 6 wk with oral cyclosporine 8 mg/kg/day, adjusted to a whole blood cyclosporine concentration (chromatography) of 200-300 ng/ml. Response was determined by the Crohn's disease activity index. Cyclosporine was measured in intestinal tissue biopsies obtained by colonoscopy at week 6 (chromatography).
Results: Eight patients responded and four did not respond. There were no significant differences between the responders and nonresponders in the mean whole blood or intestinal tissue cyclosporine concentrations. Similarly, there were no significant correlations between change in the Crohn's disease activity index score (baseline to week 6) and whole blood or intestinal tissue cyclosporine concentrations. Cyclosporine side effects, including nephrotoxicity and peroneal nerve palsy, were common.
Conclusions: Clinical response did not correlate with whole blood or intestinal tissue cyclosporine concentrations in patients treated with high-dose cyclosporine for Crohn's disease. Cyclosporine side effects, including a significant decrease in renal function, were common.