Mucosal Biomarker of Innate Immune Activation Predicts Response to Vedolizumab in Crohn’s Disease.

Mucosal Biomarker of Innate Immune Activation Predicts Response to Vedolizumab in Crohn’s Disease.

Inflamm Bowel Dis. 2019 Sep 25;:

Authors: Osterman MT, Gordon IO, Davis EM, Ciorba M, Glover SC, Abraham B, Khan F, Guo X, Yee EU, Allard FD, Claggett B, Shen B, Liu JJ

Abstract
OBJECTIVE: Mucosal barrier dysfunction plays a crucial role in intestinal inflammation in Crohn’s disease (CD). Intestinal epithelial cell (IEC) death resulting from innate immune activation, termed pyroptosis, was recently found to be a cause of this barrier defect. The aim of this study was to determine the predictive value of pretreatment ileal biopsy pyroptosis as a biomarker for clinical response to vedolizumab in CD.
DESIGN: Crohn’s disease patients ranging 18 to 80 years old from 5 IBD centers with pre-vedolizumab ileal biopsies during colonoscopy were enrolled. Biopsies were stained for activated caspases, and levels of ileal IEC pyroptosis levels were quantified. The primary outcome was clinical response 6 months after therapy, defined as a reduction of Harvey-Bradshaw Index (HBI) of ≥5 points from baseline. Secondary outcomes included clinical remission, defined as HBI <5, and endoscopic improvement, as measured by the Simple Endoscopic Score for Crohn’s Disease (SES-CD).
RESULTS: One hundred CD patients (45 male, 55 female), median age 47 (19, 78) years, were included; clinical response rate was 60%, and clinical remission was 36%. The response rate in patients with ileal pyroptosis <14 positive cells per 1000 IECs was significantly higher than those above the threshold: 89% (25 of 28) vs 49% (35 of 72), odds ratio (OR) 8.8 (95% CI, 2.3-48.6; P < 0.001). Corresponding remission rates were 54% (15 of 28) vs 29% (21 of 72; OR 2.8 [1.03-7.59; P = 0.036]). For endoscopic improvement, ileal pyroptosis of 22 positive cells per 1000 IECs was the optimal threshold that determines the magnitude SES-CD change.
CONCLUSIONS: Ileal biopsy IEC pyroptosis was predictive of clinical response and endoscopic improvement to vedolizmab in CD patients.

PMID: 31553433 [PubMed – as supplied by publisher]

PubMed Link: https://www.ncbi.nlm.nih.gov/pubmed/31553433?dopt=Abstract