P128. The value of a central image management system (CIMS) in the conduct of randomized controlled trials of therapy for ulcerative colitis (UC)
B. Feagan1, W. Sandborn2, G. D'Haens3, J. McDonald1, P. Rutgeerts4, P. Munkholm5, U. Mittmann6, D. King1, C. Wong1, L. Shackelton1, D. Gilgen7, 1Robarts Clinical Trials, London, Canada, 2UCSD Inflammatory Bowel Disease Center, La Jolla, United States, 3University of Amsterdam, Amsterdam, Netherlands, 4University Hospitals Leuven, Leuven, Belgium, 5Herlev University Hospital, Copenhagen, Denmark, 6Mittmann Pharma Consulting, Basel, Switzerland, 7Tillotts Pharma AG, Rheinfelden, Switzerland
Interobserver variation in endoscopic assessment of UC disease activity is well documented, and has likely contributed to the heterogeneity of placebo rates observed in UC clinical trials to date. We examined the potential benefits of central review of endoscopic images on patient selection and trial outcomes.
We utilized data from a placebo-controlled randomized trial of Asacol®, an 800 mg formulation of mesalamine, conducted in patients with mildly-to-moderately active UC (NCT01059344). Eligible patients had a UC-DAI total score of 4–10 and an endoscopy sub-score ≥2. Patients were randomized 1:1 to Asacol® 4.8 g/day or placebo for 10 weeks. Outcomes were assessed at weeks 6 and 10. Post-hoc exploratory analyses compared week 6 clinical and endoscopic outcomes in site investigator (SI)- and central reader (CR)-defined endoscopically eligible populations, as well as outcomes in CR-eligible patients using SI versus CR scoring.
A total of 281 patients comprised the SI population. Of these, 194 (69%) were considered eligible by the CR and were included in CR-based analyses. The effect size (percent difference Asacol® minus placebo) was consistently greater for all outcomes in the CR-versus SI-defined population (see Table 1). Placebo rates were uniformly greater in the SI population due to inclusion of patients with low endoscopic disease activity as judged by the CR. No difference in effect size was observed between CR- and SI-based outcomes at week 6 in the CR-defined population.
|Proportion [n (%)] of patients achieving efficacy endpoints by FCP cut off|
|FCP < 50 at Wk 8 (n = 36)||FCP ≥ 50 at Wk 8 (n = 158)||FCP < 150 at Wk 8 (n = 67)||FCP ≥ 150 at Wk 8|
|CRem at Wk 8||24 (66.7)||32 (20.3)||38 (56.7)||18 (14.2)|
|ERem at Wk 8||17 (47.2)||16 (10.1)||26 (38.8)||7 (5.5)|
|MH at Wk 8||28 (77.8)||68 (43.0)||52 (77.6)||44 (34.6)|
Central review of endoscopic images has the potential to minimize the inclusion of patients with low disease activity who increase placebo rates, and to improve the efficiency of UC clinical trials by reducing interobserver variability.
The rights to Asacol®, including the rights to the trademark Asacol®, are not owned by Tillotts Pharma AG in the following countries: Switzerland, USA, UK, Canada, Italy, Belgium, the Netherlands, and Luxembourg