Responsiveness of different disease activity indices in moderate-to-severe ulcerative colitis

Virginia Solitano; Remo Panaccione; Bruce E Sands; Zhongya Wang; Malcolm Hogan; Guangyong Zou; Laurent Peyrin-Biroulet; Silvio Danese; Linda J Cornfield; Brian G Feagan; Siddharth Singh; Vipul Jairath; Christopher Ma

doi:10.1016/j.medj.2024.09.001

Responsiveness of different disease activity indices in moderate-to-severe ulcerative colitis

Med. 2024 Sep 26:S2666-6340(24)00345-3. doi: 10.1016/j.medj.2024.09.001. Online ahead of print.

Authors

Affiliations

¹ Department of Medicine, Division of Gastroenterology, Western University, London, ON, Canada; Alimentiv, Inc., London, ON, Canada; Division of Gastroenterology and Gastrointestinal Endoscopy, IRCCS Ospedale San Raffaele, Università Vita-Salute San Raffaele, Milan, Italy.
² Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
³ Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁴ Alimentiv, Inc., London, ON, Canada.
⁵ Alimentiv, Inc., London, ON, Canada; Department of Epidemiology and Biostatistics, Western University, London, ON, Canada.
⁶ Department of Gastroenterology and INSERM NGERE U1256, University Hospital of Nancy, University of Lorraine, Nancy, France.
⁷ Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy.
⁸ Department of Medicine, Division of Gastroenterology, Western University, London, ON, Canada; Alimentiv, Inc., London, ON, Canada; Department of Epidemiology and Biostatistics, Western University, London, ON, Canada.
⁹ Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA.
¹⁰ Alimentiv, Inc., London, ON, Canada; Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada. Electronic address: [email protected].

PMID: 39368474
DOI: 10.1016/j.medj.2024.09.001

Abstract

Background: Clinical, endoscopic, histological, and composite instruments are currently used to measure disease activity in patients with ulcerative colitis (UC). We compared the responsiveness of the Mayo Clinic score (MCS), modified MCS (mMS; excluding physician global assessment), partial MCS (pMS; MCS without endoscopic subscore), Robart's Histopathology Index (RHI), and UC-100 score to change after ustekinumab treatment in patients with moderately to severely active UC.

Methods: Post hoc analysis of the phase 3 UNIFI induction trial (ClinicalTrials.gov: NCT02407236) was conducted. Participants with moderately to severely active UC were randomized to receive ustekinumab or placebo. Treatment assignment was the criterion to assess responsiveness, which was quantified using the probability of a treated participant having a larger change in score than a placebo participant, termed the win probability (WinP), and estimated using nonparametric methods.

Findings: The UC-100 score demonstrated large responsiveness (WinP 0.72 [95% confidence interval: 0.66-0.78]), and the MCS (0.68 [0.62-0.73]), mMS (0.69 [0.63-0.75]), and pMS (0.65 [0.59-0.71]) demonstrated similar effect sizes. Of the component items of the Mayo score, the endoscopic subscore (WinP 0.76 [0.69-0.82]) and the stool frequency subscore (WinP 0.74 [0.69-0.79]) were the most responsive. The Inflammatory Bowel Disease Questionnaire (IBDQ) quality-of-life questionnaire was also responsive (WinP 0.78 [0.72-0.82]).

Conclusions: UC disease activity indices are similarly responsive. Depending on the treatment setting, time point of evaluation, and feasibility of measurement, different scores may be used to demonstrate response. These results support the use of mMS as a composite primary endpoint, incorporating both patient-reported and endoscopic outcome measures. The UC-100 score may be more appropriate in settings that also routinely incorporate histological evaluation.

Funding: There is no funding for this study.

Keywords: Mayo Clinic score; RHI; Translation to patients; UC-100; disease activity index; endoscopy; histology; modified Mayo score; patient-reported outcome; ulcerative colitis.

Associated data

ClinicalTrials.gov/NCT02407236