TY - JOUR
T1 - Responsiveness of histological disease activity indices in ulcerative colitis
T2 - A post hoc analysis using data from the TOUCHSTONE randomised controlled trial
AU - Jairath, Vipul
AU - Peyrin-Biroulet, Laurent
AU - Zou, Guangyong
AU - Mosli, Mahmoud
AU - Vande Casteele, Niels
AU - Pai, Reetesh K.
AU - Valasek, Mark A.
AU - Marchal-Bressenot, Aude
AU - Stitt, Larry W.
AU - Shackelton, Lisa M.
AU - Khanna, Reena
AU - D'Haens, Geert R.
AU - Sandborn, William J.
AU - Olson, Allan
AU - Feagan, Brian G.
AU - Pai, Rish K.
N1 - Publisher Copyright:
© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - 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.
AB - 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.
KW - Histopathology
KW - Ulcerative colitis
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U2 - 10.1136/gutjnl-2018-316702
DO - 10.1136/gutjnl-2018-316702
M3 - Article
C2 - 30076171
AN - SCOPUS:85052307963
SN - 0017-5749
VL - 68
SP - 1162
EP - 1168
JO - Gut
JF - Gut
IS - 7
ER -