Interferon beta-1a for the maintenance of remission in patients with Crohn's disease: results of a phase II dose-finding study

Claudia Pena Rossi, Stephen B Hanauer, Ratko Tomasevic, John O Hunter, Ira Shafran, Hans Graffner, Claudia Pena Rossi, Stephen B Hanauer, Ratko Tomasevic, John O Hunter, Ira Shafran, Hans Graffner

Abstract

Background: Crohn's disease (CD) and multiple sclerosis (MS) share common pathogenic processes. Interferon (IFN) beta-1a is effective and generally well tolerated in patients with MS and has been shown to down-regulate the expression of interleukin-12, a cytokine that is thought to be involved in mucosal degeneration in CD. IFN beta-1a therefore offers promise as a treatment for CD.

Methods: In this multicentre, double-blind, placebo-controlled, phase II, dose-finding study, patients with steroid-induced clinical remissions of CD were randomized 1:1:1:1 to subcutaneous IFN beta-1a: 66 mcg three times weekly (tiw), 44 mcg tiw, 44 mcg twice weekly (biw), or matching placebo tiw with steroid tapering. The primary endpoint was the proportion of patients relapse-free at Week 26. Safety was also assessed.

Results: This study was terminated early following a planned interim analysis at 26 weeks. Of the planned 192 patients, 67 were randomized to treatment: placebo (n = 16), or IFN beta-1a 44 mcg biw (n = 17), 44 mcg tiw (n = 16) or 66 mcg tiw (n = 18). In total, 20/67 patients (29.9%) completed 26 weeks and 7 patients (10.4%) completed 52 weeks. The proportion of patients who remained relapse-free at Week 26 did not differ significantly between the placebo group (5/16, 31%) and the IFN beta-1a 44 mcg biw (6/17, 35%; p = 0.497), 44 mcg tiw (7/16, 44%; p = 0.280) or 66 mcg tiw (2/18, 11%; p = 0.333) groups. There was little difference between treatment groups in secondary efficacy endpoints. IFN beta-1a was generally well tolerated at all doses. Adverse events (AEs) were generally mild or moderate in IFN beta-1a-treated patients, with the most common AEs (influenza-like symptoms, headache, injection-site reactions) being similar to those reported with IFN beta-1a in MS.

Conclusion: There was no difference in efficacy between patients with CD receiving IFN beta-1a or placebo. However, these results should be considered in the context of the low patient numbers and high dropout rate. Overall, IFN beta-1a was generally well tolerated, with a safety profile that was consistent with previous experience in MS.

Trial registration: ClinicalTrials.gov NCT00304252.

Figures

Figure 1
Figure 1
Patient disposition. biw: twice weekly. IFN: interferon. tiw: three times weekly.
Figure 2
Figure 2
Proportion of patients who maintained remission (relapse-free) at Week 26 or Week 52 and did not receive additional treatment for Crohn's disease. biw: twice weekly; IFN: interferon; tiw: three times weekly. *p < 0.05 in favour of placebo over IFN beta-1a 66 mcg tiw at Week 52.

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