Interferon beta-1a in ulcerative colitis: a placebo controlled, randomised, dose escalating study

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: IFN-beta-1a may represent a promising novel treatment approach in ulcerative colitis.

Figure 1

Study flow chart. All patients received 22 μg of study drug three times a week (tiw) for four weeks. If patients did not show clinical improvement the dose was doubled every two weeks to up to 88 μg tiw. “Improvement” was defined as a decrease in the clinical component of the ulcerative colitis scoring system (UCSS) score (that is, stool frequency, rectal bleeding, and physician’s global assessment) by at least 1 point. If clinical symptoms improved, a sigmoidoscopy was performed. If patients were in remission by the combined UCSS score, a study end point was reached. Otherwise, the treatment dose was kept stable for two or four more weeks, respectively. The maximum duration of treatment was eight weeks and the minimum duration was four weeks. End points: remission was defined as a UCSS score of 0 for the clinical component as well as a score of 0 or 1 in the endoscopic part of the UCSS score. Clinical response was defined as a decrease of 3 or more points from baseline in the clinical components of the UCSS score. Patients discontinued due to adverse events were advanced to study end examination, including complete assessment of the UCSS.