TY - JOUR
T1 - Early ultrasound response and progressive transmural remission after treatment with ustekinumab in Crohn's disease
AU - Kucharzik, Torsten
AU - Wilkens, Rune
AU - D'Agostino, Maria-Antonietta
AU - Maconi, Giovanni
AU - Le Bars, Manuela
AU - Lahaye, Marjolein
AU - Bravatà, Ivana
AU - Nazar, Maciej
AU - Ni, Lioudmila
AU - Ercole, Elena
AU - Allocca, Mariangela
AU - Machková, Naděžda
AU - de Voogd, Floris Ae
AU - Carolina, Palmela
AU - Vaughan, Rose
AU - Maaser, Christian
N1 - Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.
PY - 2023/1
Y1 - 2023/1
N2 - BACKGROUND & AIMS: In this STARDUST substudy, the effect of ustekinumab on transmural bowel inflammation was assessed in adults with moderate-to-severe Crohn's disease (CD) by using intestinal ultrasound (IUS), a noninvasive imaging procedure.METHODS: STARDUST was an international, multicenter, phase 3b, interventional, randomized controlled trial specifically designed to compare treat-to-target and standard-of-care treatment strategies in ustekinumab-treated CD patients. In this substudy, the most affected bowel segment at baseline by IUS was used for all analyses. Key IUS endpoints (centrally read, parameter-blinded) were IUS response, transmural remission, bowel wall thickness (BWT), blood flow, bowel wall stratification, and inflammatory fat.RESULTS: Seventy-seven patients were evaluated. IUS response could be determined 4 weeks after treatment initiation, with progressive improvement through week 48. IUS response and transmural remission rates at week 48 were 46.3% and 24.1%, respectively. IUS response, transmural remission, BWT, and blood flow normalization rates were more pronounced in the colon and biologic-naive patients. Fair/moderate reliability (κ = 0.21-0.51) was observed between week 4 IUS response and week 48 overall endoscopic response and fecal calprotectin/complete biomarker outcomes. Endoscopy and IUS baseline agreement was >90% in determining the terminal ileum as the most affected bowel segment. IUS response absence at week 4 was associated with no endoscopic response (based on the simplified endoscopic score for Crohn's disease terminal ileum subscore) at week 48 (negative predictive value = 73%).CONCLUSIONS: In this first international, multicenter, interventional study, IUS showed that ustekinumab-treated CD patients achieved progressive IUS response (46.3%) and transmural remission (24.1%) through week 48, with a more robust response in the colon and biologic-naive patients.CLINICALTRIALS: gov number: NCT03107793.
AB - BACKGROUND & AIMS: In this STARDUST substudy, the effect of ustekinumab on transmural bowel inflammation was assessed in adults with moderate-to-severe Crohn's disease (CD) by using intestinal ultrasound (IUS), a noninvasive imaging procedure.METHODS: STARDUST was an international, multicenter, phase 3b, interventional, randomized controlled trial specifically designed to compare treat-to-target and standard-of-care treatment strategies in ustekinumab-treated CD patients. In this substudy, the most affected bowel segment at baseline by IUS was used for all analyses. Key IUS endpoints (centrally read, parameter-blinded) were IUS response, transmural remission, bowel wall thickness (BWT), blood flow, bowel wall stratification, and inflammatory fat.RESULTS: Seventy-seven patients were evaluated. IUS response could be determined 4 weeks after treatment initiation, with progressive improvement through week 48. IUS response and transmural remission rates at week 48 were 46.3% and 24.1%, respectively. IUS response, transmural remission, BWT, and blood flow normalization rates were more pronounced in the colon and biologic-naive patients. Fair/moderate reliability (κ = 0.21-0.51) was observed between week 4 IUS response and week 48 overall endoscopic response and fecal calprotectin/complete biomarker outcomes. Endoscopy and IUS baseline agreement was >90% in determining the terminal ileum as the most affected bowel segment. IUS response absence at week 4 was associated with no endoscopic response (based on the simplified endoscopic score for Crohn's disease terminal ileum subscore) at week 48 (negative predictive value = 73%).CONCLUSIONS: In this first international, multicenter, interventional study, IUS showed that ustekinumab-treated CD patients achieved progressive IUS response (46.3%) and transmural remission (24.1%) through week 48, with a more robust response in the colon and biologic-naive patients.CLINICALTRIALS: gov number: NCT03107793.
KW - Adult
KW - Biological Products
KW - Colon
KW - Crohn Disease/diagnostic imaging
KW - Humans
KW - Remission Induction
KW - Reproducibility of Results
KW - Treatment Outcome
KW - Ustekinumab/therapeutic use
KW - Transmural Remission
KW - Crohn's Disease
KW - Intestinal Ultrasound
KW - STARDUST
UR - http://www.scopus.com/inward/record.url?scp=85137410168&partnerID=8YFLogxK
U2 - 10.1016/j.cgh.2022.05.055
DO - 10.1016/j.cgh.2022.05.055
M3 - Journal article
C2 - 35842121
SN - 1542-3565
VL - 21
SP - 153-163.e12
JO - Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
JF - Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
IS - 1
ER -