Infliximab as rescue therapy in hospitalised patients with steroid-refractory acute ulcerative colitis: a long-term follow-up of 211 Swedish patients.

BACKGROUND: Rescue therapy with infliximab (IFX) has been proven effective in a steroid-refractory attack of ulcerative colitis (UC). The long-term efficacy is not well described. AIM: To present a retrospective study of IFX as rescue therapy in UC. Primary end points were colectomy-free survival at 3 and 12 months. METHODS: In this multicentre study, 211 adult patients hospitalised between 1999 and 2010 received IFX 5 mg/kg as rescue therapy due to a steroid-refractory, moderate-to-severe attack of UC. Exclusion criteria were duration of current flare for >12 weeks, corticosteroid treatment for >8 weeks before hospitalisation, previous IFX therapy or Crohn's disease. RESULTS: Probability of colectomy-free survival at 3 months was 0.71 (95% CI, 0.64-0.77), at 12 months 0.64 (95% CI, 0.57-0.70), at 3 years 0.59 (95% CI, 0.52-0.66) and at 5 years 0.53 (95% CI, 0.44-0.61). Steroid-free, clinical remission was achieved in 105/211 (50%) and 112/209 (54%) patients at 3 and 12 months respectively. Of 75 colectomies during the first year, 48 (64%) were carried out during the first 14 days, 13 (17%) on days 15-90 and 14 (19%) between 3 and 12 months. There were three (1.4%) deaths during the first 3 months. CONCLUSIONS: Infliximab is an effective rescue treatment, both short- and long-term, in a steroid-refractory attack of UC. Most IFX failures underwent surgery during the first 14 days, which calls for studies on how to optimise induction treatment with IFX. Serious complications, including mortality, were rare.

High dose ursodeoxycholic acid in primary sclerosing cholangitis does not prevent colorectal neoplasia.

BACKGROUND: Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) have a high risk of developing colorectal cancer and dysplasia. Ursodeoxycholic acid (UDCA) has been suggested to have chemopreventive effects on the development of colorectal cancer and dysplasia but long-term data and larger trials are lacking. AIM: To evaluate the effect of high dose (17-23 mg/kg/day) UDCA on colorectal neoplasia in a cohort of patients with PSC and IBD. METHODS: From our previous 5-year randomised controlled trial of UDCA vs. placebo in PSC, we performed a follow-up of 98 patients with concomitant IBD from entry of the trial 1996-1997 until 2009 for development of colorectal cancer or dysplasia. RESULTS: The total follow-up time was 760 person-years. Dysplasia/cancer-free survival was compared between placebo- (n = 50) and UDCA-treated (n = 48) patients. There was a similar frequency of dysplasia or cancer after 5 years between patients originally assigned to UDCA or placebo (13% vs. 16%) and no difference in dysplasia/cancer-free survival (P = 0.46, log rank test). At the end of 2009 no difference in cancer-free survival was detected, 30% of the placebo patients compared with 27% of UDCA patients had developed colorectal cancer or dysplasia. CONCLUSIONS: Long-term high dose ursodeoxycholic acid does not prevent colorectal cancer or dysplasia in patients with primary sclerosing cholangitis-associated inflammatory bowel disease.

Clinical trial: colectomy after rescue therapy in ulcerative colitis - 3-year follow-up of the Swedish-Danish controlled infliximab study.

BACKGROUND: The long-term efficacy of infliximab as rescue therapy in steroid-refractory ulcerative colitis is not well described. AIM: To examine the long-term efficacy of infliximab as a rescue therapy through a 3-year follow-up of a previous placebo-controlled trial of infliximab in acute steroid-refractory ulcerative colitis. METHOD: In the original study, 45 patients were randomized to a single infusion of infliximab 5 mg/kg or placebo, and at 3 months, 7/24 patients given infliximab were operated vs. 14/21 patients given placebo. Three years or later, patients were asked to participate in a clinical follow-up. RESULTS: Another seven patients underwent colectomy during follow-up: five in the infliximab group and two in the placebo group. After 3 years, a total of 12/24 (50%) patients given infliximab and 16/21 (76%) given placebo (P = 0.012) had a colectomy. None of eight patients in endoscopic remission at 3 months later had a colectomy compared with 7/14 (50%) patients who were not in remission (P=0.02). There was no mortality. CONCLUSION: The benefit of rescue therapy with infliximab in steroid-refractory acute ulcerative colitis remained after 3 years. The main advantage of infliximab treatment occurred during the first 3 months, whereas subsequent colectomy rates were similar in the two groups. Mucosal healing at 3 months influenced later risk of colectomy.

High prevalence of metabolic complications in patients with non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is considered to be the liver component of the metabolic syndrome and is frequently associated with obesity, dyslipidemia and type II diabetes mellitus (NIDDM). We aimed to determine the development of liver function tests (LFTs) and metabolic complications in patients previously diagnosed with NAFLD. METHODS: One-hundred-and-two patients with NAFLD diagnosed in the period 1994-2001 were identified. Eighty were brought in for new investigations, including LFTs, blood pressure, BMI, lipid profile, blood glucose and insulin. Original liver biopsy was re-evaluated. RESULTS: Sixty-two patients (77%) were males (median age 46 years; mean follow-up time 2.8 +/- 1.2 years). Fifty-four patients (68%) were light to moderately overweight with body mass index (BMI) 25-30 kg/m. Mean BMI (28.2) was the same at diagnosis and at follow-up (28.3). At the new examination, 18 patients (23%) had developed diabetes mellitus type II (n = 6) or had impaired fasting glucose (IFG) (n = 12), compared to only 2 patients at diagnosis. Hyperinsulinemia was observed in 19 patients (24%). Dyslipidemia, with elevated triglycerides and/or hypercholesterolemia, was now present in 65 patients (81%). Twenty-two patients (27%) had hypertension compared to 9 (11%) at diagnosis. Liver biopsy was performed in 24%, and 89% of those fulfilled the criteria for NASH. However, mild inflammation and fibrosis was observed, grade 1-2 (n = 17), stage I-II (n = 13) and none had cirrhosis. CONCLUSION: A significant proportion of patients with both clinical and histological diagnosis of NAFLD develop metabolic problems soon after diagnosis. These patients should be screened regularly for metabolic disorders.