Long-term budesonide treatment of collagenous colitis: a randomised, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of long-term budesonide therapy for the maintenance of clinical remission in patients with collagenous colitis. DESIGN: Randomised, placebo-controlled study with a 24-week, blinded follow-up period without any treatment. SETTING: Three gastroenterology clinics in Denmark. PATIENTS: Forty-two patients with histologically confirmed collagenous colitis and diarrhoea (more than three stools/day). INTERVENTIONS: Patients in clinical remission after 6 weeks' open-label therapy with oral budesonide (Entocort CIR capsules, 9 mg/day) received 24 weeks' double-blind maintenance therapy with budesonide 6 mg/day or placebo. Thereafter, patients entered the 24-week, blinded follow-up period. MAIN OUTCOME MEASURE: The proportion of patients in clinical remission (three or fewer stools/day) at the end of maintenance therapy. FINDINGS: A total of 34 patients in remission at week 6 were randomly assigned to budesonide 6 mg/day (n = 17) or placebo (n = 17). After 24 weeks' maintenance treatment, the proportions of patients in clinical remission were 76.5% (13 of 17) with budesonide and 12% (2 of 17) with placebo (p<0.001). At 48 weeks (the end of the follow-up period, without any treatment) these values were 23.5% (4 of 17) and 12% (2 of 17), respectively (p = 0.6). The median times to relapse after stopping active treatment (6 plus 24 weeks in the budesonide group; 6 weeks in the placebo group) were 39 and 38 days, respectively. Long-term treatment with budesonide was well tolerated. CONCLUSIONS: Long-term maintenance therapy with oral budesonide is efficacious and well tolerated for preventing relapse in patients with collagenous colitis. The risk of relapse after 24 weeks' maintenance treatment is similar to that observed after 6 weeks' induction therapy.

Azathioprine treatment during lactation.

BACKGROUND: Thiopurines are widely used to maintain remission in inflammatory bowel disease. Treatment during pregnancy is generally recommended to improve the chance of a normal birth outcome, but advice concerning breastfeeding is conflicting. Aim To estimate the exposure of breastfed infants to 6-mercaptopurine, as a metabolite of azathioprine, from maternal milk. METHODS: Eight lactating women with inflammatory bowel disease receiving maintenance therapy with azathioprine 75-200 mg daily were studied. Milk and plasma samples were obtained 30 and 60 min after drug administration and hourly for the following 5 h. RESULTS: The variation in the bioavailability of the drug was reflected in a wide range of peak plasma values of 6-mercaptopurine within the first 3 h. A similar curve, but with an hour's delay and at significantly lower concentrations varying from 2-50 microg/L, was seen in maternal milk. After 6 h an average of 10% of the peak values were measured. CONCLUSIONS: The major part of 6-mercaptopurine in breast milk is excreted within the first 4 h after drug intake. On the basis of maximum concentration measured, the infant ingests mercaptopurine of <0.008 mg/kg bodyweight/24 h. The findings confirm that breastfeeding during treatment with azathioprine seems safe and should be recommended, considering the extensive beneficial effects.

Hepatobiliary dysfunction and primary sclerosing cholangitis in patients with Crohn's disease.

BACKGROUND: Only a few studies have attempted to determined the prevalence of long-standing abnormal liver function and primary sclerosing cholangitis (PSC) in patients with Crohn's disease (CD). The aim of the study was to determine the prevalence of long-standing abnormal liver function test results and to describe the clinical, biochemical, and histologic findings in patients with large-duct classic PSC and small-duct PSC (that is, normal cholangiogram) in patients with CD during a 15-year period. METHODS: Patients with CD and long-standing abnormal liver function results were investigated individually with endoscopic retrograde cholangiography and liver biopsy. RESULTS: Of 262 consecutive patients with CD, 38 (15%) had long-standing increased alkaline phosphatase (ALP) values (mean, 1065 U/l; range, 321-4165 U/l). Of these, 10 patients were classified as having hepatic disease (4%), of which 9 had PSC and 1 had a non-specific reactive hepatitis. Of nine patients with PSC (3.4%), three were classified as having large-duct PSC; five, small-duct PSC; and one, unclassified. In patients with large-bowel CD (n = 102) the prevalence of PSC was 9%. Mean age at diagnosis of PSC was 35 years (22-46 years), and the female to male ratio, 7:2. All PSC patients had large-bowel involvement (P < 0.00015), and two of them developed colonic carcinoma of the large bowel (P < 0.01). All cases of small-duct PSC were stage 1, whereas large-duct PSC were stage 2-3. During the observation period (mean, 5.4 years) no PSC patients died. CONCLUSIONS: The results of our study indicate that PSC is the major hepatic disease in patients with CD and long-standing abnormal liver function tests and is approximately as prevalent as in ulcerative colitis. Patients with PSC and CD may have a milder liver disease than patients with PSC and ulcerative colitis, perhaps because large-duct PSC is less common in patients with CD. Cholangiograms and liver biopsies are both needed to evaluate the extent of the disease.

[Sclerosing cholangitis and ulcerative colitis. Regional prevalence]. / Skleroserende cholangitis og colitis ulcerosa. Et regionalt materiale.

The aim of the study was to determine the prevalence of primary sclerosing cholangitis (PSC) in a regional population of patients with ulcerative colitis (UC). Three hundred and five patients with UC followed over a 12 year period were examined for elevations of serum alkaline phosphatase (> 280 U/l). Twenty four such patients were found. If no cause of these elevations were found by initial investigations, endoscopic retrograde cholangiography was performed in order to determine whether they had PSC. Eleven patients were found to have PSC (3.6%), of whom five had progressive disease, including two deaths from cholangio-carcinoma, during a six-year observation period. We found no certain relation between the extent, duration or activity of ulcerative colitis and the presence of PSC. Alkaline phosphatases were elevated up to 3.7 times the upper reference level, the aminotransferases were only found to be mildly elevated.

[Primary sclerosing cholangitis]. / Primaer skleroserende cholangitis.

Primary sclerosing cholangitis (PSC) is an uncommon disorder of unknown etiology, characterized by chronic inflammation and fibrosis of the intra- and extrahepatic bile ducts. PSC is commonly associated with chronic inflammatory bowel disease, especially ulcerative colitis, and often in younger men with an extensive colitis. The diagnosis is made by endoscopic retrograde cholangiography. The characteristic findings are multiple strictures and dilatations of the intra- and extrahepatic bile ducts. Patients with PSC usually have a cholestatic biochemical profile. The liver biopsy findings are often non-specific. Different survivals in these patients have been described. However, asymptomatic patients seems to have a more favorable prognosis. The only curative treatment is liver transplantation.