| Summary: | 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.
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