Abstract | BACKGROUND: Combining clinical, endoscopic, and histological data associated with ulcerative colitis disease activity in a composite index could be a more sensitive way to detect efficacy in small numbers of patients during early drug development. Our aim was to derive and externally validate a novel index for this purpose. METHODS: Index development was done with data from a phase 2 placebo-controlled trial of ozanimod in patients with moderate-to-severe ulcerative colitis (n=179). Multivariable logistic regression modelling determined associations between candidate index items and absence of rectal bleeding (Mayo Clinic rectal bleeding subscore of 0), with items with a p value of less than 0·10 being taken forward into the final model. Model fit was internally validated and then externally validated in an independent phase 2 clinical trial dataset ( MLN02, n=146) by measuring the area under the curve of the receiver operating characteristic (AUROC). FINDINGS: In the derivation cohort, multivariable analysis indicated that the Mayo Clinic stool frequency subscore (odds ratio [OR] 0·43, 95% CI 0·30-0·61; p<0·0001) and the Robarts histopathology index (0·97, 0·93-1·01; p=0·09) were associated with absence of rectal bleeding. Although the Mayo Clinic endoscopic subscore was not significantly associated with rectal bleeding in multivariable analysis (0·74, 0·43-1·27; p=0·27), it was entered into the final model on the basis of the established diagnostic and prognostic significance of endoscopic findings. With these parameters, we established the composite UC-100 score (1 + 16 × Mayo Clinic stool frequency subscore [0 to 3] + 6 × Mayo Clinic endoscopic subscore [0 to 3] + 1 × Robarts histopathology index score [0 to 33]), which ranges from 1 (no disease activity) to 100 (severe disease activity). The UC-100 score strongly discriminated absence of rectal bleeding in both the development (AUROC 0·82, 95% CI 0·75-0·88) and validation cohorts (0·86, 0·80-0·92). A UC-100 score of 25 or less corresponds to a 95% probability of absence of rectal bleeding. INTERPRETATION: We have developed and validated a novel composite disease activity index (the UC-100 score) with good discriminative performance that could used in early phase trials of ulcerative colitis. FUNDING: None.
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Authors | Vipul Jairath, Jenny Jeyarajah, Guangyong Zou, Claire E Parker, Allan Olson, Reena Khanna, Geert R D'Haens, William J Sandborn, Brian G Feagan |
Journal | The lancet. Gastroenterology & hepatology
(Lancet Gastroenterol Hepatol)
Vol. 4
Issue 1
Pg. 63-70
(Jan 2019)
ISSN: 2468-1253 [Electronic] Netherlands |
PMID | 30343116
(Publication Type: Journal Article, Validation Study)
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Copyright | Copyright © 2019 Elsevier Ltd. All rights reserved. |
Topics |
- Adult
- Colitis, Ulcerative
(complications, diagnosis, drug therapy, pathology)
- Drug Development
- Endoscopy, Gastrointestinal
- Female
- Gastrointestinal Hemorrhage
(etiology)
- Humans
- Logistic Models
- Male
- Middle Aged
- Remission Induction
- Severity of Illness Index
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