Rutgeerts, P.

SummaryBackgroundReliable tools for patient selection are critical for clinical drug trials.AimTo evaluate a consensus‐based, standardised magnetic resonance enterography (MRE) protocol for selecting patients for inclusion in Crohn's disease (CD) multicenter clinical trials.MethodsThis study recruited 20 patients [Crohn's Disease Activity Index (CDAI) scores: <150 (n = 8); 150–220 (n = 4); 220–450 (n = 8)], to undergo ileocolonoscopy and two MREs (with and without colonic contrast) within a 14‐day period. Procedures were scored centrally using, Magnetic Resonance Index of Activity (MaRIA), and both Crohn's Disease Endoscopic Index of Severity (CDEIS) and Simplified Endoscopic Score (SES‐CD).Results37 MREs were acquired. Both MREs were evaluable in 16 patients for calculation of test–retest and inter‐reader reliability scores. The MaRIA scores for the terminal ileum had excellent test–retest and inter‐reader reliability, with correlations >0.9. The proximal ileum showed strong within‐reader agreement (0.90–0.96), and fair between‐reader agreement (0.59–0.72). MRE procedures were tolerable. MaRIA scores correlated with CDEIS and SES‐CD (0.63 and 0.71), but not with CDAI (0.34). MRE identified 3 patients with intra‐abdominal complications, who would otherwise have been included in clinical trials. Furthermore, both MRE and ileocolonoscopy identified active bowel wall inflammation in 2 patients with CDAI <150, and none in 1 patient with CDAI > 220. Data quality was good/excellent in 85% of scans, and fair or better in 96%.ConclusionsMagnetic resonance enterography of high‐quality and reproducibility was feasible in a global multi‐ centre setting, with evidence for improved selectivity over CDAI and ileocolonoscopy in identifying appropriate CD patients for inclusion in therapeutic intervention trials.

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.