Anti-TNF Therapies Promote a Proximal-to-Distal Healing Pattern in Moderate-to-Severe Ulcerative Colitis

Q: What healing pattern did the study observe in ulcerative colitis?

UC healing followed a proximal-to-distal pattern, with the highest endoscopic improvement in the descending colon and the lowest in the rectum.

Q: How did conventional MES compare with the 3-segment MES approach?

No segmental MES approach outperformed conventional MES for detecting treatment effects in the trials.

Q: Why are combined endpoints useful in assessing treatment benefit?

Combining MES ≤1 with Patient-Reported Outcome 2 (PRO2) normalization captured therapeutic benefits better than PRO2 alone.

Sep 28, 2026

Uploaded by Lucas Martin

Ulcerative colitis (UC) is a chronic inflammatory disease that extends proximally from the rectum, yet its healing pattern remains insufficiently defined. This post hoc analysis of HIBISCUS I/II and GARDENIA evaluates anti-TNF therapy effects using endoscopic improvement endpoints, comparing conventional Mayo endoscopic score (MES) with a 3-segment MES approach. Anti-TNF treatment improved EI versus placebo at week 10, but no segmental method outperformed conventional MES. Combined MES and PRO2 normalization better captured benefit than PRO2 alone, and UC healing followed a proximal-to-distal trajectory.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusions

Lay Summary

Key Messages

What is already known?

What is new here?

How can this study help patient care?

Introduction

Anti-TNF Therapies Promote a Proximal-to-Distal Healing Pattern in Moderate-to-Severe Ulcerative Colitis Emily C. L. Wong, BHSc1,, Parambir S. Dulai, MD2, John K. Marshall, MD, MSc1, Vipul Jairath, MD, PhD3, Walter Reinisch, MD, PhD4,†,, Neeraj Narula, MD, MPH1, *,†, 1Division of Gastroenterology, Department of Medicine and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada 2Division of Gastroenterology, Northwestern University, Chicago, IL, United States 3Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada 4Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria *Corresponding author: Neeraj Narula, MD, MPH, McMaster University Medical Centre, 1280 Main Street West, Unit 3V42, Hamilton, ON, Canada L8S 4K1 ([neeraj.narula@medportal.ca](neeraj.narula@medportal.ca)) . †W. R. and N. N contributed equally. Abstract Background: Ulcerative colitis (UC) is a chronic inflammatory disease of the colonic mucosa, extending proximally from the rectum. However, the segmental pattern of healing in UC remains unclear. Endoscopic improvement (EI), a key therapeutic endpoint, is typically assessed using the Mayo endoscopic score (MES), which scores the worst affected area and may miss partial/segmental healing. This study evaluates healing patterns in UC and compares conventional MES with a 3-segment MES approach for detecting treatment effects in clinical trials. Methods: A post hoc analysis of HIBISCUS I/II and GARDENIA trials was conducted in UC patients with moderate-to-severe disease (MES >2 up to the descending colon) . The primary outcome was the proportion of anti-tumor necrosis factor–treated participants achieving MES ≤1 in the descending colon, sigmoid colon, and rectum at week 10. Secondary outcomes included conventionally measured EI, segmental MES improvements, clinical response, and Patient-Reported Outcome 2 (PRO2) normalization. Outcomes were compared between adalimumab, infliximab, and placebo groups. Results: Among 300 participants, 217 received infliximab or adalimumab, while 83 received placebo. Healing followed a proximal-to-distal pattern, with the highest EI in the descending colon and the lowest in the rectum. Infliximab-treated patients continued this trend at week 54. Anti-tumor necrosis factor therapy significantly improved EI vs placebo (42 .9% vs 19.3%; P< .001) . No segmental MES approach outperformed conventional MES for detecting treatment effects. Combined endpoints (MES ≤1 + PRO2 normalization) better captured therapeutic benefits than PRO2 alone (28 .6% vs 13.3%; P = .006) . Conclusions: UC healing follows a proximal-to-distal pattern. Conventional MES remains superior for detecting treatment effects over segmental MES. Further studies should explore alternative endoscopic scoring methodologies. Key words: ulcerative colitis, Mayo endoscopic score, endoscopic improvement Lay Summary Anti-tumor necrosis factor therapies in moderate-to-severe ulcerative colitis promote a proximal-to-distal healing pattern. The conventional Mayo endoscopic score best detects treatment effects over segmental scoring. Combining the Mayo endoscopic score with clinical symptom scores enhances therapeutic benefit assessment in clinical trials. Received for publication: May 20, 2025. Editorial Decision: August 01, 2025. © The Author(s) 2025. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. 88 Wong et al. Key Messages What is already known? • Ulcerative colitis (UC) typically extends i

FAQs

What healing pattern did the study observe in ulcerative colitis?

UC healing followed a proximal-to-distal pattern, with the highest endoscopic improvement in the descending colon and the lowest in the rectum.

How did conventional MES compare with the 3-segment MES approach?

No segmental MES approach outperformed conventional MES for detecting treatment effects in the trials.

Why are combined endpoints useful in assessing treatment benefit?

Combining MES ≤1 with Patient-Reported Outcome 2 (PRO2) normalization captured therapeutic benefits better than PRO2 alone.

Sep 28, 2026

Uploaded by Lucas Martin