Matrix Metalloproteinase 3 Predicts Therapeutic Response in Inflammatory Bowel Disease Patients Treated With Infliximab.


Journal

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

Informations de publication

Date de publication:
11 04 2020
Historique:
received: 28 04 2019
pubmed: 11 9 2019
medline: 9 7 2021
entrez: 11 9 2019
Statut: ppublish

Résumé

Inflammatory bowel diseases (IBDs) are treated with anti-TNF agents. Strategies to monitor response to therapy may improve clinical control of the disease and reduce economical costs. Previous evidence suggests cleavage of infliximab (IFX) by Matrix Metalloproteinase 3 (MMP3) as a mechanism leading to loss of response. Our study aimed to evaluate if MMP3 serum levels could be considered an early marker of anti-TNF nonresponse and to analyze the correlation with other biochemical markers of treatment failure such as IFX trough levels and anti-IFX antibodies, inflammatory markers, and albumin levels. Retrospectively, 73 IBD patients who had received IFX for at least 1 year were enrolled: 35 patients were responders and 38 were nonresponders at 52 weeks. Clinical and biochemical data (Harvey-Bradshaw index [HBI], Mayo score, body mass index [BMI], C-reactive protein [CRP], fecal calprotectin and albumin levels), MMP3 serum levels, and drug monitoring were assessed at baseline, postinduction, and 52 weeks. The MMP3 levels were similar at baseline (19.83 vs 17.92 ng/mL), but at postinduction, patients who failed to respond at 1 year had significantly higher levels than patients who responded (26.09 vs 8.68 ng/mL, P < 0.001); the difference was confirmed at week 52 (29.56 vs 11.48 ng/mL, P < 0.001). The MMP3 levels tended to be higher in patients without antidrug antibodies than in patients with antidrug antibodies at postinduction and 52 weeks. The MMP3 serum determination may represent an early marker of response to infliximab.

Sections du résumé

BACKGROUND AND AIMS
Inflammatory bowel diseases (IBDs) are treated with anti-TNF agents. Strategies to monitor response to therapy may improve clinical control of the disease and reduce economical costs. Previous evidence suggests cleavage of infliximab (IFX) by Matrix Metalloproteinase 3 (MMP3) as a mechanism leading to loss of response. Our study aimed to evaluate if MMP3 serum levels could be considered an early marker of anti-TNF nonresponse and to analyze the correlation with other biochemical markers of treatment failure such as IFX trough levels and anti-IFX antibodies, inflammatory markers, and albumin levels.
METHODS
Retrospectively, 73 IBD patients who had received IFX for at least 1 year were enrolled: 35 patients were responders and 38 were nonresponders at 52 weeks. Clinical and biochemical data (Harvey-Bradshaw index [HBI], Mayo score, body mass index [BMI], C-reactive protein [CRP], fecal calprotectin and albumin levels), MMP3 serum levels, and drug monitoring were assessed at baseline, postinduction, and 52 weeks.
RESULTS
The MMP3 levels were similar at baseline (19.83 vs 17.92 ng/mL), but at postinduction, patients who failed to respond at 1 year had significantly higher levels than patients who responded (26.09 vs 8.68 ng/mL, P < 0.001); the difference was confirmed at week 52 (29.56 vs 11.48 ng/mL, P < 0.001). The MMP3 levels tended to be higher in patients without antidrug antibodies than in patients with antidrug antibodies at postinduction and 52 weeks.
CONCLUSIONS
The MMP3 serum determination may represent an early marker of response to infliximab.

Identifiants

pubmed: 31504536
pii: 5556462
doi: 10.1093/ibd/izz195
doi:

Substances chimiques

Albumins 0
Biomarkers 0
Gastrointestinal Agents 0
Leukocyte L1 Antigen Complex 0
C-Reactive Protein 9007-41-4
Infliximab B72HH48FLU
MMP3 protein, human EC 3.4.24.17
Matrix Metalloproteinase 3 EC 3.4.24.17

Types de publication

Journal Article Observational Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

756-763

Informations de copyright

© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Auteurs

Brigida Barberio (B)

Division of Gastroenterology, Department of Surgery, Oncological and Gastroenterological Sciences, University of Padua, Italy.

Renata D'Incà (R)

Division of Gastroenterology, Department of Surgery, Oncological and Gastroenterological Sciences, University of Padua, Italy.

Sonia Facchin (S)

Division of Gastroenterology, Department of Surgery, Oncological and Gastroenterological Sciences, University of Padua, Italy.

Marianna Dalla Gasperina (M)

Division of Gastroenterology, Department of Surgery, Oncological and Gastroenterological Sciences, University of Padua, Italy.

Cedric Arsenè Fohom Tagne (CA)

Division of Gastroenterology, Department of Surgery, Oncological and Gastroenterological Sciences, University of Padua, Italy.

Romilda Cardin (R)

Division of Gastroenterology, Department of Surgery, Oncological and Gastroenterological Sciences, University of Padua, Italy.

Matteo Ghisa (M)

Division of Gastroenterology, Department of Surgery, Oncological and Gastroenterological Sciences, University of Padua, Italy.

Greta Lorenzon (G)

Division of Gastroenterology, Department of Surgery, Oncological and Gastroenterological Sciences, University of Padua, Italy.

Carla Marinelli (C)

Division of Gastroenterology, Department of Surgery, Oncological and Gastroenterological Sciences, University of Padua, Italy.

Edoardo Vincenzo Savarino (EV)

Division of Gastroenterology, Department of Surgery, Oncological and Gastroenterological Sciences, University of Padua, Italy.

Fabiana Zingone (F)

Division of Gastroenterology, Department of Surgery, Oncological and Gastroenterological Sciences, University of Padua, Italy.

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Classifications MeSH