Katherine Li1, Colleen Marano1, Hongyan Zhang1, Feifei Yang1, William J Sandborn2, Bruce E Sands3, Brian G Feagan4, David T Rubin5, Laurent Peyrin-Biroulet6, Joshua R Friedman7, Gert De Hertogh8. 1. Immunology, Janssen Research & Development, LLC, Spring House, Pennsylvania. 2. Division of Gastroenterology, University of California San Diego, La Jolla, California. 3. Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York. 4. Robarts Clinical Trials, Robarts Research Institute, Western University, London, Ontario, Canada. 5. Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, Illinois. 6. Gastroenterology Department and Inserm U1256 Nutrition, Genetics, and Environmental Risk Exposure, Nancy University Hospital, Université de Lorraine, Nancy, France. 7. Immunology, Janssen Research & Development, LLC, Spring House, Pennsylvania. Electronic address: joshfriedman@me.com. 8. Deparment of Pathology, University Hospitals KU Leuven, Belgium. Electronic address: gert.dehertogh@uzleuven.be.
Abstract
BACKGROUND & AIMS: Ustekinumab induces and maintains histologic improvement in patients with ulcerative colitis (UC). The clinical relevance of this endpoint alone, and in combination with endoscopic improvement, is unknown. METHODS: Histologic disease activity was evaluated in 2630 colonic biopsy samples from patients with UC treated in the UNIFI phase 3 UC clinical studies of ustekinumab. We evaluated associations between histologic improvement (defined as the composite of neutrophil infiltration in less than 5% of crypts and no crypt destruction, erosions, ulcerations, or granulation tissue) and clinical endpoints at the end of induction (week 8 and 16) and maintenance (week 44) periods. We assessed the validity of a combined histologic and endoscopic (Mayo endoscopy subscore, 0 or 1) improvement endpoint, which we called histo-endoscopic mucosal healing (or histo-endoscopic mucosal improvement). RESULTS: Histologic improvement was significantly (P < .0001) associated with clinical remission, lower mean disease activity scores, and greater improvement in disease activity at the end of induction and maintenance studies. Ustekinumab induced and maintained significantly higher rates of histologic improvement at induction week 8 and maintenance week 44 than placebo when more stringent definitions of histologic improvement were used. Histologic improvement and endoscopic improvement following induction were associated with 10% to 20% higher rates of histo-endoscopic mucosal healing, clinical remission, and corticosteroid-free remission at week 44 (all P < .05) in patients who received ustekinumab maintenance therapy. At week 44, 61% of patients (56/92) with histo-endoscopic mucosal healing after induction therapy achieved clinical remission, versus 39% of patients (9/23, P = .0983) and 34% of patients (24/71, P = .0009) with endoscopic or histologic improvement alone after induction, respectively. CONCLUSION: Data from the UNIFI program of ustekinumab in patients with UC treated with ustekinumab indicated the achievement of histo-endoscopic mucosal healing after induction therapy is associated with lower disease activity at the end of maintenance therapy than either histologic or endoscopic improvement alone. ClinicalTrials.gov number: NCT02407236.
BACKGROUND & AIMS:Ustekinumab induces and maintains histologic improvement in patients with ulcerative colitis (UC). The clinical relevance of this endpoint alone, and in combination with endoscopic improvement, is unknown. METHODS: Histologic disease activity was evaluated in 2630 colonic biopsy samples from patients with UC treated in the UNIFI phase 3 UC clinical studies of ustekinumab. We evaluated associations between histologic improvement (defined as the composite of neutrophil infiltration in less than 5% of crypts and no crypt destruction, erosions, ulcerations, or granulation tissue) and clinical endpoints at the end of induction (week 8 and 16) and maintenance (week 44) periods. We assessed the validity of a combined histologic and endoscopic (Mayo endoscopy subscore, 0 or 1) improvement endpoint, which we called histo-endoscopic mucosal healing (or histo-endoscopic mucosal improvement). RESULTS: Histologic improvement was significantly (P < .0001) associated with clinical remission, lower mean disease activity scores, and greater improvement in disease activity at the end of induction and maintenance studies. Ustekinumab induced and maintained significantly higher rates of histologic improvement at induction week 8 and maintenance week 44 than placebo when more stringent definitions of histologic improvement were used. Histologic improvement and endoscopic improvement following induction were associated with 10% to 20% higher rates of histo-endoscopic mucosal healing, clinical remission, and corticosteroid-free remission at week 44 (all P < .05) in patients who received ustekinumab maintenance therapy. At week 44, 61% of patients (56/92) with histo-endoscopic mucosal healing after induction therapy achieved clinical remission, versus 39% of patients (9/23, P = .0983) and 34% of patients (24/71, P = .0009) with endoscopic or histologic improvement alone after induction, respectively. CONCLUSION: Data from the UNIFI program of ustekinumab in patients with UC treated with ustekinumab indicated the achievement of histo-endoscopic mucosal healing after induction therapy is associated with lower disease activity at the end of maintenance therapy than either histologic or endoscopic improvement alone. ClinicalTrials.gov number: NCT02407236.
Authors: Cristian Hernández-Rocha; Shadi Nayeri; Williams Turpin; Mike Steel; Krzysztof Borowski; Joanne M Stempak; James Conner; Mark S Silverberg Journal: J Crohns Colitis Date: 2022-08-04 Impact factor: 10.020
Authors: Christopher Ma; Rocio Sedano; Ahmed Almradi; Niels Vande Casteele; Claire E Parker; Leonardo Guizzetti; David F Schaeffer; Robert H Riddell; Reetesh K Pai; Robert Battat; Bruce E Sands; Christophe Rosty; Marla C Dubinsky; Florian Rieder; Noam Harpaz; Maria T Abreu; Robert V Bryant; Gregory Y Lauwers; Richard Kirsch; Mark A Valasek; Eileen Crowley; William J Sandborn; Brian G Feagan; Rish K Pai; Vipul Jairath Journal: Gastroenterology Date: 2021-02-19 Impact factor: 22.682
Authors: Olga Maria Nardone; Alina Bazarova; Pradeep Bhandari; Rosanna Cannatelli; Marco Daperno; Jose Ferraz; Martin Goetz; Xianyong Gui; Bu Hayee; Gert De Hertogh; Mark Lazarev; Ji Li; Adolfo Parra-Blanco; Luca Pastorelli; Remo Panaccione; Vincenzo Occhipinti; Timo Rath; Samuel C L Smith; Uday N Shivaji; Gian Eugenio Tontini; Michael Vieth; Vincenzo Villanacci; Davide Zardo; Raf Bisschops; Ralf Kiesslich; Subrata Ghosh; Marietta Iacucci Journal: United European Gastroenterol J Date: 2022-02-23 Impact factor: 4.623