IBD

10 - Small Bowel Innate Immune Activation Predicts Clinical Response to Vedolizumab Therapy in Crohn’s Disease

Monday, October 8
10:18 AM - 10:30 AM
Location: Terrace Ballroom (level 400)

Category: IBD
Julia J. Liu, MD1, Matthew Ciorba, MD2, Sarah C. Glover, DO3, Bincy Abraham, MD, MS4, Freeha Khan, MD5, Quinton Palmer, MD1, Xueyan Guo, MD6, Eric Yee, MD1, Felicia D. Allard, MD1, Brian Claggett7, Bo Shen, MD8, Ilyssa O. Gordon, MD, PhD5
1University of Arkansas for Medical Sciences, Little Rock, AR; 2Washington University, St. Louis, MO; 3University of Florida, Gainesville, FL; 4Houston Methodist Hospital, Houston, TX; 5Cleveland Clinic, Cleveland, OH; 6UAMS, Xi’an, Shaanxi, China (People's Republic); 7Brigham & Women's Hospital, Boston, MA; 8Cleveland Clinic Digestive Disease Institute, Cleveland, OH

Award: Category Award (IBD)

Introduction: Intestinal barrier dysfunction plays a crucial role in the development of mucosal inflammation in Crohn’s disease (CD). Recently, intestinal epithelial cell (IEC) pyroptosis - an inflammatory form of cell death mediated by innate immune activation was proposed as a possible cause of this barrier defect. We hypothesize that small bowel IEC pyroptosis may serve as a marker of mucosal barrier dysfunction and help to guide the selection of biologic therapy in CD patients. Vedolizumab is an anti-integrin monoclonal antibody approved for treatment of ulcerative colitis and CD. The aim of this multi-centered study was to determine the predictive value of pre-treatment ileal biopsy IEC pyrotposis for clinical response to vedolizumab in CD.

Methods: Adult CD patients 18 to 75 years of age from 4 IBD centers who underwent colonoscopy with ileal biopsies prior to initiation of vedolizumab therapy were enrolled.   Clinical response, defined as a reduction of Harvey-Bradshaw Index (HBI) by ≥ 5 points from pre-treatment baseline, was determined at ≥ 6 months after treatment initiation by chart review.  Intestinal biopsy samples were sectioned and stained for IEC pyroptosis with the Maximus barrier assay kit (Maximus Diagnostics LLC). Samples with at least 10 intact villi per patient were analyzed by blinded pathologists for quantitation of mucosal innate immune activation. The primary study end-point was clinical response to vedolizumab therapy stratified by pre-treatment mucosal IEC pyroptosis.

Results: 50 CD patients with a median age of 45 (19, 75) years, 24 M and 26 F were included in this analysis. Biopsies from 5 patients were insufficient for analysis. The overall clinical response rate in the remaining 45 patients was 56%.  The clinical response rate in patients with IEC pyroptosis below the cut point of 18 was significantly higher compared to those above: 75% (15/20) versus 40% (10/25), Odds Ratio = 4.5 (1.2, 16.4), p=0.02. IEC pyroptosis in responders and non-responders were 16±11 versus 26±10 positive cells / 1000 IECs, respectively (p=0.003). Pyroptosis of 33 was associated with absolute non-response (5/45, 11%). Elimination of the absolute non-responders could improve the clinical response of the study cohort from 56% to 63%.

Discussion: Mucosal biopsy IEC pyroptosis can predict clinical response to vedolizmab therapy in Crohn's patients.


Disclosures:
Julia Liu: Maximus Diagnostics LLC – Patent Holder. Takeda – Grant/Research Support.
Matthew Ciorba: AbbVie – Grant/Research Support, Speaker's Bureau. Incyte – Grant/Research Support. Takeda – Consultant, Grant/Research Support, Speaker's Bureau.
Sarah Glover: AbbVie – Grant/Research Support. Celgene – Grant/Research Support. Genetech – Grant/Research Support. Gilead – Grant/Research Support. Janssen – Grant/Research Support. Shire – Grant/Research Support. Takeda – Advisory Committee/Board Member, Consultant, Grant/Research Support. UCB – Grant/Research Support.
Bincy Abraham: Abbvie – Speaker's Bureau. Janssen – Advisory Committee/Board Member, Grant/Research Support, Speaker's Bureau. Samsung bioepis – Consultant. Takeda – Consultant, Grant/Research Support, Speaker's Bureau. UCB – Advisory Committee/Board Member, Consultant, Speaker's Bureau.
Freeha Khan indicated no relevant financial relationships.
Quinton Palmer indicated no relevant financial relationships.
Xueyan Guo indicated no relevant financial relationships.
Eric Yee indicated no relevant financial relationships.
Felicia Allard indicated no relevant financial relationships.
Brian Claggett indicated no relevant financial relationships.
Bo Shen indicated no relevant financial relationships.
Ilyssa Gordon indicated no relevant financial relationships.

Julia J. Liu

Associate Professor
University of Arkansas for the Medical Sciences
Little Rock, Arkansas

Julia Liu, MD, MSc, FRCPC, FACG, FACP, FASGE, is an Associate Professor at the University of Arkansas for Medical Sciences, and a staff gastroenterologist at the University Hospital and the Central Arkansas Veterans Healthcare Systems. Her research and clinical interest focuses on understanding the pathogenesis of leaky gut in chronic gastrointestinal disorders such as inflammatory bowel disease and irritable bowel syndrome.

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