Responsiveness of histological disease activity indices in ulcerative colitis: a post hoc analysis using data from the TOUCHSTONE randomised controlled trial.
OBJECTIVE
We evaluated the reliability and responsiveness of available but incompletely validated UC histological disease activity indices using standardised rules for centralised assessment.


DESIGN
Disease activity was assessed in biopsies collected in a phase II placebo-controlled ozanimod trial by four blinded pathologists using the Geboes (GS) and modified Riley (MRS) scores, the Robarts Histopathology (RHI) and Nancy Histological (NHI) indices and a Visual Analogue Scale. Reliability was assessed with intraclass correlation coefficients (ICCs). Index responsiveness was evaluated by assessing longitudinal validity (Pearson correlations of changes in index scores and other disease measures), and effect size estimates (standardised effect size (SES)) using two criteria for change (treatment assignment and >2 point decrease in total Mayo Clinic score). Area under the receiver operating characteristic (AUROC) curve estimates evaluated the probability of the indices to discriminate between treatment and placebo.


RESULTS
Inter-rater reliability of the histological indices was substantial to almost perfect (ICC>0.61), and responsiveness was moderate to large (SES estimates>0.5); 0.81 (0.52, 1.10), 0.87 (0.58, 1.17), 0.57 (0.30, 0.84) and 0.81 (0.52, 1.09) when treatment assignment was the criterion for change and 1.05 (0.80, 1.31), 1.13 (0.87, 1.39), 0.88 (0.64, 1.12) and 1.06 (0.80, 1.31) for the change in Mayo score criterion for the GS, MRS, RHI and NHI, respectively. The indices had similar drisciminative ability based on AUROC estimates (range 0.608-0.649).


CONCLUSION
All four existing histological indices were similarly reliable and responsive based on this dataset.
['Jairath|Vipul|V|', 'Peyrin-Biroulet|Laurent|L|', 'Zou|Guangyong|G|', 'Mosli|Mahmoud|M|', 'Vande Casteele|Niels|N|', 'Pai|Reetesh K|RK|', 'Valasek|Mark A|MA|', 'Marchal-Bressenot|Aude|A|', 'Stitt|Larry W|LW|', 'Shackelton|Lisa M|LM|', 'Khanna|Reena|R|', "D'Haens|Geert R|GR|", 'Sandborn|William J|WJ|', 'Olson|Allan|A|', 'Feagan|Brian G|BG|', 'Pai|Rish K|RK|']
D001706:Biopsy D003093:Colitis, Ulcerative D005260:Female D006801:Humans D007189:Indans D008297:Male D008875:Middle Aged D010069:Oxadiazoles D012372:ROC Curve D015203:Reproducibility of Results D012720:Severity of Illness Index D064232:Visual Analog Scale
ulcerative colitis histopathology