Daclizumab, a humanised monoclonal antibody to the interleukin 2 receptor (CD25), for the treatment of moderately to severely active ulcerative colitis: a randomised, double blind, placebo controlled, dose ranging trial.

BACKGROUND: An uncontrolled pilot study demonstrated that daclizumab, a humanised monoclonal antibody to the interleukin 2 receptor (CD25), might be effective for the treatment of active ulcerative colitis. METHODS: A randomised, double blind, placebo controlled trial was conducted to evaluate the efficacy of daclizumab induction therapy in patients with active ulcerative colitis. A total of 159 patients with moderate ulcerative colitis were randomised to receive induction therapy with daclizumab 1 mg/kg intravenously at weeks 0 and 4, or 2 mg/kg intravenously at weeks 0, 2, 4, and 6, or placebo. The primary end point was induction of remission at week 8. Remission was defined as a Mayo score of 0 on both endoscopy and rectal bleeding components and a score of 0 or 1 on stool frequency and physician's global assessment components. Response was defined as a decrease from baseline in the Mayo score of at least 3 points. RESULTS: Two per cent of patients receiving daclizumab 1 mg/kg (p = 0.11 v placebo) and 7% of patients receiving 2 mg/kg (p = 0.73) were in remission at week 8, compared with 10% of those who received placebo. Response occurred at week 8 in 25% of patients receiving daclizumab 1 mg/kg (p = 0.04) and in 33% of patients receiving 2 mg/kg (p = 0.30) versus 44% of those receiving placebo. Daclizumab was well tolerated. The most frequently reported adverse events in daclizumab treated patients compared with placebo treated patients were nasopharyngitis (14.6%) and pyrexia (10.7%). CONCLUSION: Patients with moderate ulcerative colitis who are treated with daclizumab are not more likely to be in remission or response at eight weeks than patients treated with placebo.

Comparison of different methods expressing results of the aminopyrine breath test.

Different methods of expressing the results of the aminopyrine CO2 breath test (ABT) were compared to determine the method that would be most sensitive for evaluating liver function. The patient population included health controls (n = 22); patients with mild (4), moderate (9), and severe (7) alcoholic liver disease; and patients with chronic persistent hepatitis (7), chronic active hepatitis (18), chronic active hepatitis with bridging (18), and chronic active hepatitis with cirrhosis (17). The ABT was performed with 2 micro Ci [14C]aminopyrine or 2 mg per kg [13C]aminopyrine, and the results were expressed as the instantaneous labeled CO2 excretion rates at 30, 60, 90, and 120 min after the dose, the maximum excretion rate, and the 120-min cumulative excretion. The 30-min parameter had the highest sensitivity toward moderate alcoholic hepatitis, severe alcoholic hepatitis, chronic active hepatitis with bridging, and chronic active hepatitis with cirrhosis (96%); however, when the ABT was repeated in six normal controls with 225 ml of orange juice, the 30-min rate was significantly reduced (7.8 +/- 1.3 vs. 5.6 +/- 1.2% dose per hr), and the rate of false-positive test results was increased (0 of 6 vs. 2 of 6) indicating that gastric delay influenced the 30-min parameter. The 60-min excretion rate, maximum rate, and 120-min cumulative excretion were the next most sensitive expressions of the ABT, and were not altered by the small gastric load. Of these three expressions, the 60-min parameter was the most convenient because it required fewer samples and a shorter test period.

The aminopyrine breath test and serum bile acids reflect histologic severity in chronic hepatitis.

To determine whether the aminopyrine breath test (ABT) and serum bile acid concentrations reflect histologic severity of chronic hepatitis, 56 patients were prospectively evaluated with liver biopsies and ABTs, and the results were compared to results of standard liver chemistry tests; 44 of these patients also had fasting and 2-hr postprandial serum bile acid measurements. Mean values for the ABT were significantly lower, and serum bile acids were significantly higher in patients with chronic active hepatitis with bridging or cirrhosis than in patients with mild chronic active hepatitis or chronic persistent hepatitis. Thirty of 35 patients with bridging or cirrhosis had ABTs less than 5.7% (mean of controls -2 S.D.) and 21 of 25 with mild chronic active hepatitis or chronic persistent hepatitis had values greater than 5.7% (sensitivity 0.86, specificity 0.84). Fasting and 2-hr postprandial bile acids were also more sensitive than standard chemistries in identifying patients with bridging or cirrhosis. Thus, the ABT and serum bile acids reflect histologic severity in chronic hepatitis patients and may be helpful in selecting patients for liver biopsy.

Alcoholic hepatitis: update on recognition and management.

Alcohol consumption can cause fatty infiltration of the liver and more serious liver disorders such as alcoholic hepatitis and cirrhosis. The primary care physician familiar with the signs and symptoms can quickly institute corrective and sometimes lifesaving measures in affected patients. Management consists of detoxification, alcoholism rehabilitation, nutritional repletion, and treatment for any complications of the liver disease. In addition, several drugs now under study offer promising new approaches to treatment.