mercaptopurine and Fistula

Topics: Adolescent; Adult; Crohn Disease; Fistula; Gastric Fistula; Humans; Intestinal Fistula; Mercaptopurine; Middle Aged; Parenteral Nutrition; Skin Diseases

To determine outcome following treatment of refractory Crohn's disease with intravenous (i.v.) cyclosporine (CYA).. The medical records of 18 patients with refractory Crohn's disease treated with i.v. CYA were reviewed. Nine patients had refractory inflammatory Crohn's disease and nine patients had complex fistulizing Crohn's disease. All patients were initially treated with i.v. CYA (4 mg/kg/day). Patients who responded were converted to standard oral CYA. Patient outcomes were classified as complete response, partial response, or nonresponse.. Four of nine patients with severe inflammatory Crohn's disease and seven of nine patients with fistulizing Crohn's disease had a partial response to i.v. CYA. Four of four responding patients in the inflammatory group and four of six responding patients in the fistulizing group (plus one initial nonresponder) maintained or improved their response during oral CYA therapy. After discontinuing oral CYA, all four patients in the inflammatory group and five of seven patients in the fistulizing group relapsed despite 1-17 wk of concomitant treatment with azathioprine or 6-mercaptopurine (AZA/6MP). Two patients who received overlapping CYA and AZA/6MP for 17 and 23 wk maintained long-term responses. CYA toxicity was minimal: reversible nephrotoxicity (n = 2), headache (n = 2), oral candidiasis (n = 1), paresthesia (n = 2).. I.v. CYA appears to benefit both refractory inflammatory and fistulizing Crohn's disease. Most patients who respond to i.v. CYA will maintain their response during oral CYA therapy. However, the majority of these patients relapse when oral CYA is discontinued, probably because of inadequate duration of overlap with the slow acting maintenance drugs, AZA/6MP.

Topics: Administration, Oral; Adolescent; Adult; Azathioprine; Crohn Disease; Cyclosporine; Drug Therapy, Combination; Female; Fistula; Humans; Immunosuppressive Agents; Injections, Intravenous; Male; Mercaptopurine; Middle Aged; Treatment Outcome

To test the effectiveness of 6-mercaptopurine (6-MP) in the treatment of Crohn's disease, we entered 83 chronically ill patients into a two-year double-blind study comparing 6-MP with placebo. Crossover data showed that improvement occurred in 26 of 39 courses of 6-MP (67%) as compared with three of 39 courses of placebo (8%) (P less than 0.001). Non-crossover data likewise confirmed the superiority of 6-MP. The drug was more effective than placebo in closing fistulas (31 vs 6%) and in permitting discontinuation or reduction of steroid dosage (75 vs. 36%) (P less than 0.001). The onset of response to 6-MP was often delayed, with 32% of patients taking longer than three months to respond, and 19% taking longer than four months. Adverse side effects to 6-MP occurred in 10% of patients and were uniformly reversible. We conclude that 6-MP is an effective and useful agent in the management of Crohn's disease.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Clinical Trials as Topic; Crohn Disease; Double-Blind Method; Drug Evaluation; Drug Therapy, Combination; Female; Fistula; Follow-Up Studies; Humans; Male; Mercaptopurine; Middle Aged; Placebos; Random Allocation; Research Design; Sulfasalazine; Time Factors

Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) with uncertain etiopathogenesis. CD can involve any site of gastrointestinal tract from the mouth to anus and is associated with serious complications such as bowel strictures, perforations, and fistula formation. The incidence and prevalence rates of CD in Korea are still lower than those of Western countries, but have been rapidly increasing during the past decades. Although there are no definitive curative modalities for CD, various medical and surgical therapies are currently applied for diverse clinical situations of CD. However, a lot of decisions on the management of CD are made depending on the personal experiences and choices of physicians. To suggest preferable approaches to diverse problems of CD and to minimize the variations according to physicians, guidelines for the management of CD are needed. Therefore, IBD Study Group of the Korean Association for the Study of the Intestinal Diseases has set out to develop the guidelines for the management of CD in Korea. These guidelines were developed using the adaptation methods and encompass the treatment of inflammatory disease, stricturing disease, and penetrating disease. The guidelines also cover the indication of surgery, prevention of recurrence after surgery, and CD in pregnancy and lactation. These are the first Korean guidelines for the management of CD and the update with further scientific data and evidences is needed.

Topics: Anti-Inflammatory Agents; Antibodies, Monoclonal; Antimetabolites, Antineoplastic; Budesonide; Crohn Disease; Databases, Factual; Female; Fistula; Humans; Infliximab; Intestinal Perforation; Male; Mercaptopurine; Mesalamine; Methotrexate; Prednisolone; Pregnancy; Recurrence; Risk Factors; Severity of Illness Index; Sulfasalazine

Fistulae are distressing chronic complications of Crohn's disease which have served as one of the most common indications for surgical resection. While steroids and sulfasalazine have not been successful in closing fistulae, in a previous double-blind study 6-mercaptopurine (6-MP) was more effective than placebo in accomplishing this goal (31% vs 6%). Thirty-four patients with Crohn's disease fistulae were treated with 6-MP for a minimum period of 6 months. In 13 patients (39%) the fistulae closed completely, and in another 9 (26%) there was obvious improvement. All types of fistulae responded to 6-MP with the most impressive closures occurring in patients with fistulae of the abdominal wall and enteroenteric fistulae. The mean time to respond was 3.1 months, with 23% of patients taking longer than 4 months to show any response. Response was not related to other drugs (steroids, sulfasalazine) used in conjunction with the 6-MP. The site of intestinal involvement with Crohn's disease did not appear to play a significant role in the frequency or degree of response to 6-MP, but patients without prior resection and fistulae did better than those with fistulae occurring after surgery. The long-term response to fistulae was good if 6-MP was maintained, whereas exacerbation eventually followed discontinuation of 6-MP. 6-Mercaptopurine is an effective and useful drug in the treatment of fistulae, as it is in other manifestations of chronic unrelenting Crohn's disease.

Topics: Abdominal Muscles; Adolescent; Adult; Crohn Disease; Double-Blind Method; Female; Fistula; Humans; Intestinal Fistula; Male; Mercaptopurine; Middle Aged; Random Allocation; Rectal Fistula; Sulfasalazine; Vaginal Fistula