Cyclosporine and 6-mercaptopurine for active, refractory Crohn's colitis in children.
OBJECTIVE
This prospective, open trial of treatment was conducted to determine whether cyclosporine A (CSA) is effective in inducing remission in children with severe, active Crohn's colitis refractory to other medical treatment and if remission may be maintained by 6-mercaptopurine (6-MP) and 5-aminosalicylic acid (5-ASA) after discontinuing CSA.


METHODS
Ten children (five males, five females), ages 1.2-16 yr (mean 11), all had failed to respond to 4 wk of treatment with i.v. methylprednisolone and total parenteral nutrition/elemental diet; three were already receiving 6-mercaptopurine. CSA was initially given as a twice daily i.v. dosage and was switched to oral CSA when a clinical response was observed. At the same time, corticosteroids were switched to the oral route and tapered over the next 3 months. Patients were grouped by treatment outcome. "Responders" were those who achieved remission with i.v. CSA therapy, "relapsers" were those who achieved remission with i.v. CSA but relapsed later, and nonresponders had not achieved remission after 4 wk of i.v. CSA. Responders were given 6-MP with intent to discontinue CSA after 6 months and maintain remission by 6-MP and 5-ASA.


RESULTS
There were seven responders to CSA. For all patients, the Pediatric Crohn's Disease Activity Index (PCDAI) (score range 0-100) had a mean value of 55 (range 40-65) just before treatment; PCDAI improved to a mean of 19 (range 5-42.5) after 2 wk of CSA therapy. Four of the seven responders discontinued CSA after 6 months and remain well on 6-MP and 5ASA alone for 22, 13, 8, and 3 months. One patient had massive GI bleeding (from active Crohn's colitis), which stopped within 48 h of CSA treatment. There were three relapsers (at 2-6 months of CSA), and three were nonresponders. Three patients who were already receiving 6-MP before CSA therapy either did not respond to CSA or relapsed while receiving it. The six nonresponders and relapsers required surgical resection. Transient side effects included hypertension responding to nifedipine in one child and hirsutism and tremors in another.


CONCLUSIONS
We conclude that CSA offers a good remission rate for children with severe Crohn's colitis failing other medical treatment, although relapse was common especially if the child was already on 6-MP. In addition, CSA may offer "temporizing" therapy in severe, active Crohn's colitis; this may allow surgery to be performed electively, with time for psychosocial and nutritional preparation before surgery.
Mahdi
G
G
Division of Gastroenterology, British Columbia Children's Hospital, Vancouver, Canada.
Israel
D M
DM
Hassall
E
E
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003092:Colitis / Q000188:drug therapy; D003131:Combined Modality Therapy; D003424:Crohn Disease / Q000188:drug therapy*; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D012008:Recurrence; D012074:Remission Induction; D013997:Time Factors
D005765:Gastrointestinal Agents; D016572:Cyclosporine; D015122:Mercaptopurine