Discordance Between Patient-Reported Outcomes and Mucosal Inflammation in Patients With Mild to Moderate Ulcerative Colitis

Abstract

Background & aims: Little is known about the association between rectal bleeding and increased stool frequency with endoscopic findings in patients with mild to moderate ulcerative colitis (UC). We evaluated the associations between rectal bleeding or stool frequency and endoscopic remission in this population.

Methods: We performed a post-hoc analysis of data from a phase 3 non-inferiority trial of 817 adults with mild to moderate UC who received treatment with mesalazine. We obtained information on rectal bleeding, stool frequency, and Mayo endoscopic subscores (MESs) at weeks 0, 8, and 38. The sensitivity, specificity, and positive and negative predictive values with which rectal bleeding and stool frequency identified patients with MESs of 0 and/or 1 were calculated at weeks 8 and 38 of treatment. The associations between change in rectal bleeding and stool frequency and change in MES after treatment were quantified using the Spearman's rank correlation coefficient.

Results: Among patients with a MES of 0, 7/82 patients (9%) had a rectal bleeding score of 1 or more and 40/82 patients (49%) had a stool frequency score of 1 or more at week 8; at week 38, 6/167 patients (4%) had a rectal bleeding score of 1 or more and 63/167 patients (38%) had a stool frequency score of 1 or more. Among patients with MESs of 0 or 1, 50/310 patients (16%) had a rectal bleeding score of 1 or more and 162/310 patients (52%) had had a stool frequency score of 1 or more at week 8; at week 38, 18/363 patients (5%) had a rectal bleeding score of 1 or more and 141/363 patients (39%) had a stool frequency score of 1 or more. The Spearman rank correlation coefficients for change in rectal bleeding and stool frequency with change in MES at week 8 were 0.39 (95% CI, 0.32-0.45) and 0.34 (95% CI, 0.27-0.40), respectively. In patients with reduced MESs at week 8, 39/389 patients (10%) had unchanged or worsening rectal bleeding and 81/389 patients (21%) had unchanged or increasing stool frequencies.

Conclusions: In a post-hoc analysis of data from a phase 3 trial of adults with mild to moderate UC treated with mesalazine, we found absence of rectal bleeding to identify patients in endoscopic remission. However, many patients in remission still have increased stool frequency, indicating that it may not be a sensitive marker of disease activity in patients with mild to moderate UC.

Trial registration: ClinicalTrials.gov NCT01903252.

Keywords: Biomarker; Diarrhea; IBD; Response to Therapy.

Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.

Proportion of patients with rectal bleeding (RB) and stool frequency (SB) subscores at week 8 and 38 by Mayo endoscopic subscore (MES).

Figure 2.

Proportion of patients in endoscopic remission (MES=0 or MES=0/1) with rectal bleeding (RB) and stool frequency (SB) subscores ≥1 at week 8 and 38.

Figure 3.

Change in rectal bleeding (RB) and stool frequency (SF) at week 8 after treatment with 3.2g mesalazine compared to change in Mayo endoscopic subscore (MES).