Matrix Metalloproteinase 3 Predicts Therapeutic Response in Inflammatory Bowel Disease Patients Treated With Infliximab.
Adolescent
Adult
Albumins
/ analysis
Biomarkers
/ blood
C-Reactive Protein
/ analysis
Colitis, Ulcerative
/ blood
Crohn Disease
/ blood
Drug Monitoring
/ methods
Feces
/ chemistry
Female
Gastrointestinal Agents
/ therapeutic use
Humans
Induction Chemotherapy
Infliximab
/ therapeutic use
Leukocyte L1 Antigen Complex
/ analysis
Male
Matrix Metalloproteinase 3
/ blood
Middle Aged
Predictive Value of Tests
Retrospective Studies
Treatment Failure
Young Adult
Metalloproteinase 3
TNF failure
inflammatory bowel disease
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
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
756-763Informations de copyright
© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.