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Are Endoscopic Endpoints Reliable in Therapeutic Trials of Ulcerative Colitis?

Wolff, Sebastian MD*; Terheggen, Grischa MD; Mueller, Ralph PhD; Greinwald, Roland PhD; Franklin, Jeremy PhD§; Kruis, Wolfgang MD*

doi: 10.1097/01.MIB.0000437044.43961.00
Original Clinical Articles

Background: The consistency of endoscopic and histologic findings in patients with ulcerative colitis (UC) has not been elucidated. Choice of assessment may affect study outcomes.

Methods: Post hoc analyses were performed using data from 2 randomized, controlled multicenter trials: (1) SAG-26, mesalazine granules for induction of remission in UC (n = 380), and (2) SAG-27, mesalazine granules for maintenance of UC remission (n = 647). Assessments included Clinical Activity Index, Endoscopic Index, modified Disease Activity Index, and Histology Index.

Results: In SAG-26, 52 of 380 patients (13.7%) with clinically (Clinical Activity Index >4) and endoscopically (Endoscopic Index ≥4) active UC showed no histological signs of active inflammation (Histology Index ≤1) at baseline. Among endoscopically and histologically active patients, 246 of 327 (75.2%) reached clinical remission versus 48 of 52 patients (92.3%) with active endoscopy but no inflammation on histology (difference, 17.1%; P = 0.006). The difference in the proportion of patients achieving clinical remission according to endoscopy and histology in clinically inactive (Clinical Activity Index ≤4) patients was 30.8% in SAG-26 (at the study end) and 28.1% in SAG-27 (at baseline). In SAG-27, clinical relapse occurred in 21.2% of patients with endoscopic and histologic remission at baseline and 27.1% of patients with some histological inflammation at baseline (P = 0.111). Using the modified Disease Activity Index ≤1 (mucosal healing) instead of the Endoscopic Index score, the difference was similar (21.2% versus 28.0%, P = 0.073).

Conclusions: Endoscopic and histologic assessments differ in both active and inactive UC. Overdiagnosis of inflammation using endoscopy versus histology can significantly affect outcomes, at least in studies using induction of clinical remission as an endpoint. The assessment criteria for trials in UC should be reconsidered.

Article first published online 8 October 2013

*Department of Internal Medicine, Evangelisches Krankenhaus Kalk, Cologne, Germany;

Department of Internal Medicine, Evangelisches Krankenhaus Duesseldorf, Duesseldorf, Germany;

Department of Clinical Research & Development, Dr. Falk Pharma GmbH, Freiburg, Germany; and

§Institute of Medical Statistics, Informatics and Epidemiology, Cologne, Germany.

Reprints: Wolfgang Kruis, MD, Department of Internal Medicine, Evangelisches Krankenhaus Kalk, Buchforststrasse 2, Cologne D-51103, Germany (e-mail:

The SAG-26 and SAG-27 studies were funded by Dr. Falk Pharma GmbH, Freiburg, Germany. The current post hoc analysis received no external funding.

W. Kruis has served as a speaker and consultant for Dr. Falk Pharma, Freiburg, Germany. R. Greinwald, and R. Mueller are employees of Dr. Falk Pharma, Freiburg, Germany. The remaining authors have no conflicts of interest to disclose.

Received July 08, 2013

Accepted August 26, 2013

© Crohn's & Colitis Foundation of America, Inc.
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