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DOP031. A multicenter study to evaluate magnetic resonance enterography (MRE) for selection of Crohn's disease patients for inclusion into a therapeutic clinical trial

P. Higgins1, W.J. Sandborn2, J. Rimola3, T. Lu4, A. Coimbra4, P. Rutgeerts5, D. Luca4, D. Bruining6, S. Vermeire5, C. Santillan7, M. Al-Hawary8, J. Fidler9, D. Vanbeckevoort10, R. Vanslembrouck10, L. Peyrin-Biroulet11, V. Laurent12, A. de Crespigny4, S. O'Byrne4, J. Panes13, 1University of Michigan, Internal Medicine - Gastroenterology, Ann Arbor, MI, United States, 2University of California San Diego, Division of Gastroenterology, La Jolla, United States, 3Hospital Clínic de Barcelona, Radiology Department, Barcelona, Spain, 4Genentech, Research and Early Development, South San Francisco, United States, 5KU Leuven, Division of Gastroenterology, Leuven, Belgium, 6Mayo Clinic, Gastroenterology, Rochester, United States, 7University of California San Diego, Radiology, San Diego, United States, 8University of Michigan, Radiology, Ann Arbor, United States, 9Mayo Clinic, Radiology, Rochester, United States, 10Biomedical MRI, KU Leuven Department of Imaging and Pathology, Leuven, Belgium, 11Nancy University Hospital, Université de Lorraine, Gastroenterology and Hepatology, Vandoeuvre-les-Nancy, France, 12Brabois Hospital, Gastroenterology, Vandoeuvre les Nancy, France, 13Hospital Clínic Barcelona, Department of Gastroenterology, Barcelona, Spain

Background

The current approvable endpoint for Crohn's Disease (CD) clinical trials is the Crohn's Disease Activity Index (CDAI). There is supportive evidence that the inaccuracy of the CDAI in identifying active inflammatory CD may have led to inconclusive or erroneous activity assessment of anti inflammatory therapies [1] or novel therapies in development [2]. Magnetic resonance enterography (MRE) has shown potential to assess CD activity and complications in single center studies. The purpose of this study was to evaluate MRE as a tool to select patients for CD clinical trials in a multicenter setting.

Methods

Patients were recruited from 6 centers (3 US, 3 Europe) globally based on their pre-specified levels of disease according to a prospectively conducted CDAI (Remission: <150, mild: 150 < CDAI < 225, and moderate–severe: CDAI >225, respectively). Within a 2 week period each patient underwent an ileocolonoscopy and a pair of MREs with and without colonic distention with each procedure separated by at least 24 hours. MRE scans and ileocolonoscopy videos were scored by central readers using the MaRIA index and CDEIS, respectively. A MaRIA subsegment score >11 and CDEIS >8 were used as selection criteria demonstrating active disease for inclusion into a study of moderate to severely active CD.

Results

A total of 19 patients were enrolled across the six centers. Using ileocolonoscopy as the standard reference, MRE without enema identified deep ulcers in the colon with 58% sensitivity, 73% specificity; MRE with enema had similar sensitivity, 58% but better specificity, 80%. For enrollment into a trial for moderate to severely active CD, the CDAI identified 6 patients. Of these, only 3 patients had active disease confirmed by either MRE or Ileocolonoscopy. One of these three patients had an abscess identified by MRE. The remaining three patients had no objective evidence of disease by MRE or ileocolonoscopy. Using MRE, 12 subjects were identified for inclusion into a trial of which 3 would have been excluded from a clinical trial due to presence of an abscess or abdominal extramedullary hematopoeisis. Two of the remaining 9 subjects did not have identifiable disease on ileocolonoscopy. Using ileocolonoscopy, 6 subjects were identified of whom 2 patients would have been excluded by MRE due to an abscess. Overall, MRE selected 7 patients with active disease compared with 4 and 2 patients by CDEIS and CDAI who would be appropriate to include in a CD clinical trial.

Conclusion

In comparison to endoscopy and the CDAI, MRE better enriches for patients with more appropriate levels of disease for inclusion in a clinical trial with therapeutic intervention.

1. Colombel JF, Sandborn WJ, Reinisch W, Mantzaris GJ, Kornbluth A, Rachmilewitz D, Lichtiger S, D'Haens G, Diamond RH, Broussard DL, Tang KL, van der Woude CJ, Rutgeerts P, (2010), Infliximab, azathioprine, or combination therapy for Crohn's disease, NEJM, 1383–95

2. Sandborn WJ, Schreiber S, Feagan BG, Rutgeerts P, Younes ZH, Bloomfield R, Coteur G, Guzman JP, D'Haens GR, (2011), Certolizumab pegol for active Crohn's disease: a placebo-controlled, randomized trial, Clin Gastroenterol Hepatol, 670–678