Early Ultrasound Response and Progressive Transmural Remission After Treatment With Ustekinumab in Crohn's Disease
Torsten Kucharzik, Rune Wilkens, Maria-Antonietta D'Agostino, Giovanni Maconi, Manuela Le Bars, Marjolein Lahaye, Ivana Bravatà, Maciej Nazar, Lioudmila Ni, Elena Ercole, Mariangela Allocca, Naděžda Machková, Floris A E de Voogd, Carolina Palmela, Rose Vaughan, Christian Maaser, STARDUST Intestinal Ultrasound study group, Tomas Grega, Ivana Niangova, Rudolf Repak, Petra Matejkova, Radka Vanickova, Juel Mie Agerbæk, Annett Cannon, Vittorio Giuliano, Christoph Antoni, Jürgen Büning, Michael Gebel, Martin Grewe, Sebastian Küpper, Nikolas Ryschka, Andrej Potthoff, Wolfgang Reindl, Karolin Schliwa, Martin Schulz, Hermann Schulze, Markus Krankenhaus, Marco Affronti, Maria Laura, Christina Bezzio, Flaminia Cavallaro, Marina Coletta, Andrea Costantino, Federico Furfaro, Fabrizio Pizzolante, Steven Bots, Robert De Knegt, Ivan Bunganic, Zdenek Opravil, Joaquin Poza, Jordi Rimola, Cristina Suarez Ferrer, Torsten Kucharzik, Rune Wilkens, Maria-Antonietta D'Agostino, Giovanni Maconi, Manuela Le Bars, Marjolein Lahaye, Ivana Bravatà, Maciej Nazar, Lioudmila Ni, Elena Ercole, Mariangela Allocca, Naděžda Machková, Floris A E de Voogd, Carolina Palmela, Rose Vaughan, Christian Maaser, STARDUST Intestinal Ultrasound study group, Tomas Grega, Ivana Niangova, Rudolf Repak, Petra Matejkova, Radka Vanickova, Juel Mie Agerbæk, Annett Cannon, Vittorio Giuliano, Christoph Antoni, Jürgen Büning, Michael Gebel, Martin Grewe, Sebastian Küpper, Nikolas Ryschka, Andrej Potthoff, Wolfgang Reindl, Karolin Schliwa, Martin Schulz, Hermann Schulze, Markus Krankenhaus, Marco Affronti, Maria Laura, Christina Bezzio, Flaminia Cavallaro, Marina Coletta, Andrea Costantino, Federico Furfaro, Fabrizio Pizzolante, Steven Bots, Robert De Knegt, Ivan Bunganic, Zdenek Opravil, Joaquin Poza, Jordi Rimola, Cristina Suarez Ferrer
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: NCT03107793.
Keywords: Crohn’s Disease; Intestinal Ultrasound; STARDUST; Transmural Remission.
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Source: PubMed