Directionality of Endoscopic and Histologic Healing in Ulcerative Colitis: a Prospective Pilot Study

Objective: Endoscopic and histologic healing in ulcerative colitis (UC) is hypothesized to progress proximally to distally, with healing of the distal rectosigmoid occurring last. However, this has not been empirically verified.

Methods: We performed a prospective cohort study in patients with pancolonic UC commencing treatment with a tumor necrosis factor (TNF) antagonist or vedolizumab. Four biopsies were obtained from each of the five colonic segments at colonoscopy, both at baseline and 16-24 weeks after treatment initiation. Independent, blinded central reading of both endoscopic [modified Mayo Endoscopic Subscore (mMES) (score = 1 excludes any friability), UC Endoscopic Index of Severity (UCEIS)] and histologic disease activity [Robarts Histopathology Index (RHI), Nancy Histological Index (NHI), and Geboes Score] was performed for each colonic segment, and changes per segment were calculated.

Results: A total of eight patients were recruited (five TNF antagonists, three vedolizumab). There was no significant difference in the mean change between colonic segments for any of the endoscopic disease activity indices (P value based on Kruskal-Wallis test for differences between ascending, transverse, descending, sigmoid colon, and rectum: 0.328 for mMES and 0.317 for UCEIS). Similarly, there was no difference in change in histologic activity between colonic segments (P = 0.357 for RHI, P = 0.410 for NHI, P = 0.734 for Geboes score).

Conclusion: We did not observe evidence of an anatomical healing gradient in UC across different colonic segments, nor evidence of delayed distal improvement. Larger studies are required to validate whether the rectum truly does heal last in UC.