Increased Expression of Interleukin-13 Receptor in Ileum Associated With Nonresponse to Adalimumab in Ileal Crohn's Disease.


Journal

Inflammatory bowel diseases
ISSN: 1536-4844
Titre abrégé: Inflamm Bowel Dis
Pays: England
ID NLM: 9508162

Informations de publication

Date de publication:
01 06 2023
Historique:
received: 10 05 2022
medline: 2 6 2023
pubmed: 27 7 2022
entrez: 26 7 2022
Statut: ppublish

Résumé

The terminal ileum poses a predilection for Crohn's disease (CD) but is less susceptible to undergo healing to treatment with biologics and small molecules. This study aimed to evaluate histologic features associated with endoscopic remission (ER). This is a post hoc analysis of patients with moderately to severely active CD, defined as Crohn's disease activity index 220 to 450, and terminal ileal ulceration treated with antitumor necrosis factor (TNF)-α inhibitor adalimumab from the EXTEND trial. We studied whether baseline total Global Histologic Disease Activity Scores (GHAS), any individual histologic element, and specific immunohistochemical (IHC) markers of chronic inflammation from biopsy specimens were associated with postinduction (week 12) and maintenance (week 52) ER, defined as Simple Endoscopic Score for Crohn's Disease of 0. Multivariable logistic regression models adjusted for confounders were used to assess the relationship between histologic markers and 1-year outcomes. Seventy-one adult patients with CD affecting the ileum were included in this analysis. Both baseline ileal GHAS scores and individual histologic components were not found to be associated with ER at weeks 12 or 52. Increased expression of interleukin-13 receptor (IL-13R) on IHC stains was associated with reduced likelihood of achieving 1-year ER (adjusted odds ratio, 0.06; 95% CI, 0.01-0.92; P = .044). No other biomarker assessed was associated with 1-year ER. Ileal histologic disease activity and IHC activation markers of chronic mucosal inflammation were not associated with 1-year ER. However, strong staining for IL-13 receptor in the ileum was associated with reduced odds of 1-year ER using adalimumab. Mucosal cellular disease profiles might pose an opportunity to guide treatment of CD. In this post hoc analysis, ileal histologic disease activity and IHC activation markers of chronic mucosal inflammation were not predictive of 1-year ER. However, strong staining for IL-13R in the ileum was associated with reduced odds of 1-year ER using adalimumab.

Sections du résumé

BACKGROUND
The terminal ileum poses a predilection for Crohn's disease (CD) but is less susceptible to undergo healing to treatment with biologics and small molecules. This study aimed to evaluate histologic features associated with endoscopic remission (ER).
METHODS
This is a post hoc analysis of patients with moderately to severely active CD, defined as Crohn's disease activity index 220 to 450, and terminal ileal ulceration treated with antitumor necrosis factor (TNF)-α inhibitor adalimumab from the EXTEND trial. We studied whether baseline total Global Histologic Disease Activity Scores (GHAS), any individual histologic element, and specific immunohistochemical (IHC) markers of chronic inflammation from biopsy specimens were associated with postinduction (week 12) and maintenance (week 52) ER, defined as Simple Endoscopic Score for Crohn's Disease of 0. Multivariable logistic regression models adjusted for confounders were used to assess the relationship between histologic markers and 1-year outcomes.
RESULTS
Seventy-one adult patients with CD affecting the ileum were included in this analysis. Both baseline ileal GHAS scores and individual histologic components were not found to be associated with ER at weeks 12 or 52. Increased expression of interleukin-13 receptor (IL-13R) on IHC stains was associated with reduced likelihood of achieving 1-year ER (adjusted odds ratio, 0.06; 95% CI, 0.01-0.92; P = .044). No other biomarker assessed was associated with 1-year ER.
CONCLUSIONS
Ileal histologic disease activity and IHC activation markers of chronic mucosal inflammation were not associated with 1-year ER. However, strong staining for IL-13 receptor in the ileum was associated with reduced odds of 1-year ER using adalimumab. Mucosal cellular disease profiles might pose an opportunity to guide treatment of CD.
In this post hoc analysis, ileal histologic disease activity and IHC activation markers of chronic mucosal inflammation were not predictive of 1-year ER. However, strong staining for IL-13R in the ileum was associated with reduced odds of 1-year ER using adalimumab.

Autres résumés

Type: plain-language-summary (eng)
In this post hoc analysis, ileal histologic disease activity and IHC activation markers of chronic mucosal inflammation were not predictive of 1-year ER. However, strong staining for IL-13R in the ileum was associated with reduced odds of 1-year ER using adalimumab.

Identifiants

pubmed: 35880680
pii: 6650010
doi: 10.1093/ibd/izac157
doi:

Substances chimiques

Adalimumab FYS6T7F842
Receptors, Interleukin-13 0
Tumor Necrosis Factor-alpha 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

875-882

Commentaires et corrections

Type : ErratumIn

Informations de copyright

© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Auteurs

Emily C L Wong (ECL)

Department of Medicine, Division of Gastroenterology, and Farncombe Family Digestive Health Research Institute; McMaster University, Hamilton ON, Canada.

Arif Yusuf (A)

Department of Medicine, Division of Gastroenterology, and Farncombe Family Digestive Health Research Institute; McMaster University, Hamilton ON, Canada.

Jagoda Pokryszka (J)

Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria.

Parambir S Dulai (PS)

Division of Gastroenterology, Northwestern University, Chicago, IL, USA.

Jean-Frederic Colombel (JF)

Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

John K Marshall (JK)

Department of Medicine, Division of Gastroenterology, and Farncombe Family Digestive Health Research Institute; McMaster University, Hamilton ON, Canada.

Walter Reinisch (W)

Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria.

Neeraj Narula (N)

Department of Medicine, Division of Gastroenterology, and Farncombe Family Digestive Health Research Institute; McMaster University, Hamilton ON, Canada.

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Classifications MeSH