Role of Cyclosporine in Crohn's Disease

Abstract

Cyclosporine A has been shown anecdotally to be useful in Crohn's disease. In most studies, a clinical response is seen within a short time, one to two weeks. A feature common to all studies is frequent relapse shortly after the drug is discontinued. There are problems in dosage and bioavailability with gastrointestinal intolerance, malabsorption and variable absorption. Consequently, there is a requirement for monitoring of blood levels. There is renal toxicity, particularly when prior renal disease is present, when nephrotoxic drugs arc used concomitantly and in the elderly. A prospective, placebo controlled, international trial of cyclosporine A in patients with steroid-resistant Crohn's disease was recently published. All patients in this study had active Crohn's disease (Crohn's disease activity index greater than 150). There were 37 patients randomized to cyclosporine and 34 to placebo. The mean age, proportion with prior surgery, disease location, presence of complications and cotreatment was the same in both groups. At 12 weeks, two-thirds of the patients on cyclosporine A had responded, compared to one-third on placebo. The 'therapeutic gain', defined as "difference in effect between treatments", was significant at two weeks and remained so for one, two and three months. There is a steroid-sparing effect with this drug, as with other immunosuppressives used in Crohn's disease - a valuable side effect of this therapy. There is increasing evidence that in patients with Crohn's disease, cyclosporine A may be malabsorbed. It is, therefore, recommended that all patients be given intravenous cyclosporine for at least the first week. Once the response is present, the drug may be switched to the oral route, and a pharmacokinetic profile performed. The drug may need to be given three or four times a day in some Crohn's disease patients. In children, cyclosporine A absorption appears to be related to the length of the intestine. This has not been determined in adults. Currently, the use of cyclosporine A is limited to patients with steroid-resistant Crohn's disease presenting to tertiary referral centres with appropriate cyclosporine A monitoring facilities.