Role of Cyclosporine in Crohn's Disease

Cyclosporine A has been shown anecdotally to be useful inCrohn'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 afterthe drug is discontinued. There are problems in dosage and bioavailability withgastrointestinal intolerance, malabsorption and variable absorption. Consequently,there is a requirement for monitoring of blood levels. There is renaltoxicity, particularly when prior renal disease is present, when nephrotoxic drugsarc used concomitantly and in the elderly. A prospective, placebo controlled,international trial of cyclosporine A in patients with steroid-resistant Crohn'sdisease was recently published. All patients in this study had active Crohn'sdisease (Crohn's disease activity index greater than 150). There were 37 patientsrandomized to cyclosporine and 34 to placebo. The mean age, proportion withprior surgery, disease location, presence of complications and cotreatment wasthe same in both groups. At 12 weeks, two-thirds of the patients on cyclosporineA had responded, compared to one-third on placebo. The 'therapeutic gain',defined as "difference in effect between treatments", was significant at two weeksand remained so for one, two and three months. There is a steroid-sparing effectwith this drug, as with other immunosuppressives used in Crohn's disease - avaluable side effect of this therapy. There is increasing evidence that in patientswith Crohn's disease, cyclosporine A may be malabsorbed. It is, therefore,recommended that all patients be given intravenous cyclosporine for at least thefirst week. Once the response is present, the drug may be switched to the oralroute, and a pharmacokinetic profile performed. The drug may need to be giventhree 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 islimited to patients with steroid-resistant Crohn's disease presenting to tertiaryreferral centres with appropriate cyclosporine A monitoring facilities