A randomised placebo controlled trial of pegylated interferon alpha in active ulcerative colitis

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: PegIFN is safe but not effective, at the dosages used, in patients with ulcerative colitis.

Figure 1

Clinical remission (in per cent) (clinical activity score of <4) in patients with active ulcerative colitis treated with placebo (n = 20), pegylated interferon α (PegIFN) 0.5 μg/kg (n = 19), or PegIFN 1.0 μg/kg (n = 21) over a 12 week treatment period.

Figure 2

Endoscopic remission (defined as endoscopic activity <4) in patients treated with placebo, pegylated interferon α (PegIFN) 0.5 μg/kg, or PegIFN 1.0 μg/kg over a 12 week treatment period. Endoscopy was performed in the placebo group on day 0 in 19, on day 29 in 14, and on day 85 in 11 patients, in the PegIFN 0.5 μg/kg group on day 0 in 21, on day 29 in 18, and on day 85 in 10 patients, and in the PegIFN 1.0 μg/kg group on day 0 in 20, on day 29 in 18, and on day 85 in nine patients.