Discrepancies between patient-reported outcomes, and endoscopic and histological appearance in UC

Abstract

Objective: Both endoscopy and histology may be included in the definition of mucosal healing in UC. This study aimed to establish the association between patient-reported outcomes, specifically symptom measures, and the presence of inflammation as measured by endoscopy and histology in UC.

Design: Using patient data from an observational multicentre study of UC (n=103), rectal bleeding (RB) and stool frequency (SF) symptom subscores of the Mayo Clinic Score (MCS) were compared with the endoscopic subscore (MCSe) and histology. Faecal calprotectin and biopsy cytokine expression were also evaluated.

Results: When identifying UC patients with inactive disease, RB scores were superior to SF scores and the combination (sensitivity/specificity: MCSe=0/1, RB 77%/81%, SF 62%/95%, RB+SF 54%/95%; MCSe=0, RB 87%/66%, SF 76%/83%, RB+SF 68%/86%). Across different definitions of mucosal healing (MCSe≤1; 0; or 0 plus inactive histology), a larger subset of patients reported increased SF (39%, 25% and 27%, respectively) compared with RB (24%, 13% and 10%). Faecal calprotectin and inflammatory cytokine expression were higher in patients with active disease compared with patients with mucosal healing, but there were no differences between patients using increasingly stringent definitions of mucosal healing.

Conclusions: Endoscopically inactive disease is associated with absence of RB but not with complete normalisation of SF. Achieving histological remission did not improve symptomatic relief. In addition, in these patients, higher inflammatory biomarker levels were not observed. These data suggest that non-inflammatory changes, such as bowel damage, may contribute to SF in UC.

Keywords: DIARRHOEA; ENDOSCOPY; GASTROINTESTINAL BLEEDING; HISTOPATHOLOGY; ULCERATIVE COLITIS.

Conflict of interest statement

Competing interests: J-FC has received research funding Abbvie, Genentech, Janssen and Janssen, and Takeda and has served as a consultant for Abbvie, Amgen, Boehringer Ingelheim, Celgene Corporation, Celltrion, Enterome, Ferring, Genentech, Janssen Pharmaceuticals, Medimmune, Merck & Co., Pfizer, Protagonist, Second Genome, Seres, Takeda and Theradiag. He has also been a speaker for Abbvie, Ferring, Takeda and Shire. He has received stock options from Intestinal Biotech Development and Genfit. MEK, AS, RZ and TTL are employees of Genentech, a member of the Roche group and own Roche stock. GdH has received payment to his institution from Genentech for the central pathology review in this manuscript and his institution has received payment for his central pathology review services from Shire, Novartis, Centocor and Galapagos. WAF serves as an advisory board member for Abbvie, Janssen Pharmaceuticals and Boehringer Ingelheim Pharma and serves as a consultant for Celgene, Connecticut Children's Medical Center, Genentech, Janssen Pharmaceuticals, Shire and Velocity Pharmaceutical Development.

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Figures

Figure 1

Proportion of patients with Mayo endoscopic subscores (MCSe)=0–3 by increasing (A) rectal bleeding (RB) and (B) stool frequency (SF) subscores.

Figure 2

Proportion of patients with (A) rectal bleeding (RB) and (B) stool frequency (SF) symptoms, grouped by increasingly stringent definitions of mucosal healing. MCSe, Mayo endoscopic subscores.

Figure 3

Faecal calprotectin (FCP) levels and symptom scores. (A) Box plots (median IQR) showing FCP levels in patients with active disease (Mayo endoscopic subscores (MCSe)≥2) or different definitions of mucosal healing (MCSe≤1, MCSe=0, MCSe=0/inactive histology). *p