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
Early Ultrasound Response and Progressive Transmural Remission After Treatment With Ustekinumab in Crohn's Disease / Kucharzik, T.; Wilkens, R.; D'Agostino, M. -A.; Maconi, G.; Le Bars, M.; Lahaye, M.; Bravata, I.; Nazar, M.; Ni, L.; Ercole, E.; Allocca, M.; Machkova, N.; de Voogd, F. A. E.; Palmela, C.; Vaughan, R.; Maaser, C.; Grega, T.; Niangova, I.; Repak, R.; Matejkova, P.; Vanickova, R.; Agerbaek, J. M.; Cannon, A.; Giuliano, V.; Antoni, C.; Buning, J.; Gebel, M.; Grewe, M.; Kupper, S.; Ryschka, N.; Potthoff, A.; Reindl, W.; Schliwa, K.; Schulz, M.; Schulze, H.; Krankenhaus, M.; Affronti, M.; Laura, M.; Bezzio, C.; Cavallaro, F.; Coletta, M.; Costantino, A.; Furfaro, F.; Pizzolante, F.; Bots, S.; De Knegt, R.; Bunganic, I.; Opravil, Z.; Poza, J.; Rimola, J.; Ferrer, C. S.. - In: CLINICAL GASTROENTEROLOGY AND HEPATOLOGY. - ISSN 1542-3565. - 21:1(2023). [10.1016/j.cgh.2022.05.055]
Early Ultrasound Response and Progressive Transmural Remission After Treatment With Ustekinumab in Crohn's Disease
Furfaro F.;
2023-01-01
Abstract
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: NCT03107793I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
