An open-labeled, randomized study comparing systemic interferon-alpha-2A and prednisolone enemas in the treatment of left-sided ulcerative colitis. Interferon-beta-1a for the treatment of steroid-refractory ulcerative colitis: a randomized, double-blind, placebo-controlled trial. Interferon beta-1a in ulcerative colitis: a placebo controlled, randomised, dose escalating study. A randomised placebo controlled trial of pegylated interferon alpha in active ulcerative colitis.
The aim of this study was to compare the treatment efficacies of subcutaneous interferon-alpha-2A (IFN-alpha-2A) injections versus prednisolone enemas in active left-sided ulcerative colitis in an open-labeled, randomized study.
                Sixteen ulcerative colitis patients received IFN-alpha-2A subcutaneously (dosage: first wk, 9 MIU three times weekly [t.i.w.]; second wk, 6 MIU t.i.w.; wk 3-12, 3 MIU t.i.w.), and 16 received prednisolone enemas for 30 days (100 ml once daily, 0.25 mg of prednisolone/ml). The Powell-Tuck Index, Inflammatory Bowel Disease Questionnaire (IBDQ) score, and rectal histological activities were assessed before and after treatment. Thirteen patients in the IFN-alpha-2A group and all 16 in the prednisolone enema group completed the treatment.
                IFN-alpha-2A treatment showed significant improvements in the Powell-Tuck Index (p = 0.0002), IBDQ score (p = 0.002), and rectal histological activity scores (p = 0.02). In the enema group, significant improvements were found in the Powell-Tuck Index (p = 0.0009), whereas no significant improvements were detected in the IBDQ scores (p = 0.055) or rectal histological scores (p = 0.052). There were no differences between scores of the two groups either before or after treatment. Only moderate side effects from the IFN-alpha-2A treatment were seen during the first 2-4 wk of treatment.
                IFN-alpha-2A treatment resulted in significant depression of the disease activity as reflected by the Powell-Tuck Index, IBDQ score, and histological disease activity scoring. The preliminary trial thus suggests that IFN-alpha-2A may be effective in the treatment of active left-sided ulcerative colitis. Larger, randomized trials are, however, warranted to confirm this finding, owing to possible type II errors in group comparisons. We performed a randomized, double-blind, placebo-controlled, multicenter trial to investigate the efficacy and safety of recombinant interferon-beta-1a (rIFN-beta-1a) in outpatients with active steroid-refractory ulcerative colitis.
                Ninety-one randomized patients subcutaneously received 3 MIU rIFN-beta-1a (group A, n = 32), 1 MIU rIFN-beta-1a (group B, n = 30), or placebo (group C, n = 29) 3 times a week over a period of 8 weeks in addition to standard therapy. An intention-to-treat analysis was performed to evaluate the efficacy and safety of treatment. Results: In all 3 groups, the median prestudy clinical activity index (CAI) was 10. In 18 of 32 patients (56%) in group A, in 11 of 30 patients (36%) in group B, and in 10 of 29 patients (34%) in group C, a reduction of the CAI of 6 points or greater (response) was achieved (differences were not statistically significant). Complete response (reduction of CAI to < or =4) was achieved in 56%, 30%, and 38% of patients in groups A, B, and C, respectively. Compared with baseline, the median endoscopic index had been reduced by 5, 3, and 4 points in groups A, B, and C, respectively. Steroid reduction was 12 mg in group A, 6 mg in group B, and 10 mg in group C. Identical side effects occurred in all 3 groups. Seven serious adverse events were reported (1 in group A and 6 in group C). All were unrelated to therapy as judged by the investigating physicians.
                rIFN-beta-1a was safe but not significant, at the dosage and/or duration of treatment used, in steroid-refractory ulcerative colitis. Further studies are indicated. and aims: Administration of interferon (IFN)-beta may represent a rational approach to the treatment of ulcerative colitis through its immunomodulatory and anti-inflammatory effects. The present study was performed to evaluate the efficacy and tolerability of IFN-beta-1a.
                Patients (n=18) with moderately active ulcerative colitis were randomised to receive IFN-beta-1a or placebo. IFN-beta-1a was started at a dose of 22 micro g three times a week subcutaneously, and the dose was increased at two week intervals to 44 micro g and then to 88 micro g if no response was observed. The maximum duration of treatment was eight weeks. End points were clinical treatment response, defined as a decrease of at least 3 points from baseline in the ulcerative colitis scoring system (UCSS) symptoms score and induction of endoscopically confirmed remission.
                Baseline characteristics and disease severity were similar in both groups. Data from 17 patients are included in this report (10 patients in the IFN-beta-1a group and seven patients in the placebo group). Clinical response was achieved in five patients (50%) in the IFN-beta-1a group and in one (14%) in the placebo group (P=0.14). Remission was achieved in three patients in the IFN-beta-1a group and in none in the placebo group (p=0.02). Most adverse reactions associated with IFN-beta-1a were influenza-like symptoms or injection site reactions, and were mild or moderate in severity.
                IFN-beta-1a may represent a promising novel treatment approach in ulcerative colitis. Pilot studies of interferon alpha (IFN-alpha) suggest a high remission rate in the treatment of active ulcerative colitis. We evaluated the safety of pegylated interferon alpha (PegIFN) and its role in induction of remission in patients with active ulcerative colitis, in a multicentre placebo controlled trial.
                Sixty patients with a clinical activity score (CAI) of >6 were randomised to receive placebo (n=20), PegIFN 0.5 microg/kg (n=19), or PegIFN 1.0 microg/kg body weight (n=21) once weekly (PegIntron; Schering-Plough, USA) over 12 weeks. Patients receiving 5-aminosalicylates, steroids, and/or azathioprine in stable dosages were included.
                Serious adverse events were seen in none of the placebo patients, in 3/19 patients in the PegIFN 0.5 microg/kg group (hospitalisation due to disease flare up n=3), and in 3/21 in the PegIFN 1.0 microg/kg group (hospitalisation due to disease flare up n=1; thrombosis n=1; grand mal seizure n=1). Otherwise, we observed only minor IFN-alpha side effects. Clinical remission rates at week 12 (CAI < or =4) were 7/20 (35%) in the placebo, 9/19 (47%) in the PegIFN 0.5 microg/kg group, and 7/21 (33%) in the PegIFN 1.0 microg/kg group (NS). Early withdrawal from the study was observed in 11/20 placebo patients, in 6/19 in the PegIFN 0.5 microg/kg group, and in 10/21 in the PegIFN 1.0 microg/kg group, mainly due to lack of efficacy. The higher PegIFN dose was associated with a significant decrease in levels of C reactive protein (p=0.003, day 0 v 85).
                PegIFN is safe but not effective, at the dosages used, in patients with ulcerative colitis.