Actual Anti-TNF Trough Levels Relate to Serum IL-10 in Drug-Responding Patients With Crohn's Disease.
Crohn’s disease
adalimumab
inflammation
infliximab
interleukin 10
Journal
Inflammatory bowel diseases
ISSN: 1536-4844
Titre abrégé: Inflamm Bowel Dis
Pays: England
ID NLM: 9508162
Informations de publication
Date de publication:
17 07 2019
17 07 2019
Historique:
received:
20
11
2018
pubmed:
19
2
2019
medline:
23
4
2020
entrez:
19
2
2019
Statut:
ppublish
Résumé
Patients with Crohn's disease (CD) responding to anti-tumor necrosis factor (anti-TNF) show great variability in serum drug levels, even within the therapeutic range. We aimed at exploring the role of inflammatory, genetic, and bacterial variables in relation to anti-TNF through levels in CD patients. Consecutive CD patients receiving stable doses of infliximab or adalimumab were included. Clinical and analytical parameters were recorded. Cytokine response, bacterial DNA translocation, and several immune-related genes' genotypes were evaluated, along with serum through anti-TNF drug levels. A linear regression analysis controlled by weight and drug regimen was performed. One hundred nineteen patients were initially considered. Five patients on infliximab and 2 on adalimumab showed antidrug antibodies in serum and were excluded. One hundred twelve patients were finally included (62 on infliximab, 50 on adalimumab). Fourteen patients on infliximab and 15 on adalimumab (22.6% vs 30%, P = 0.37) were receiving an intensified drug regimen. C-reactive protein (CRP), fecal calprotectin, Crohn's Disease Activity Index, leukocyte count, and albumin levels in plasma were not significantly associated with infliximab or adalimumab levels in the multivariate analysis. Serum interleukin-10 (IL-10) levels were directly related to infliximab (Beta = 0.097, P < 0.0001) and adalimumab levels (Beta = 0.069, P = 0.0241). The best multivariate regression model explaining the variability of serum infliximab and adalimumab levels included IL-10. Predicted drug levels by this model robustly fitted with actual drug levels (R2 = 0.841 for infliximab, R2 = 0.733 for adalimumab). Serum IL-10 is significantly related to serum anti-TNF levels in CD patients, showing how the disposition of anti-TNF drugs is significantly influenced by the degree of immunological activation.
Sections du résumé
BACKGROUND
Patients with Crohn's disease (CD) responding to anti-tumor necrosis factor (anti-TNF) show great variability in serum drug levels, even within the therapeutic range. We aimed at exploring the role of inflammatory, genetic, and bacterial variables in relation to anti-TNF through levels in CD patients.
METHODS
Consecutive CD patients receiving stable doses of infliximab or adalimumab were included. Clinical and analytical parameters were recorded. Cytokine response, bacterial DNA translocation, and several immune-related genes' genotypes were evaluated, along with serum through anti-TNF drug levels. A linear regression analysis controlled by weight and drug regimen was performed.
RESULTS
One hundred nineteen patients were initially considered. Five patients on infliximab and 2 on adalimumab showed antidrug antibodies in serum and were excluded. One hundred twelve patients were finally included (62 on infliximab, 50 on adalimumab). Fourteen patients on infliximab and 15 on adalimumab (22.6% vs 30%, P = 0.37) were receiving an intensified drug regimen. C-reactive protein (CRP), fecal calprotectin, Crohn's Disease Activity Index, leukocyte count, and albumin levels in plasma were not significantly associated with infliximab or adalimumab levels in the multivariate analysis. Serum interleukin-10 (IL-10) levels were directly related to infliximab (Beta = 0.097, P < 0.0001) and adalimumab levels (Beta = 0.069, P = 0.0241). The best multivariate regression model explaining the variability of serum infliximab and adalimumab levels included IL-10. Predicted drug levels by this model robustly fitted with actual drug levels (R2 = 0.841 for infliximab, R2 = 0.733 for adalimumab).
CONCLUSION
Serum IL-10 is significantly related to serum anti-TNF levels in CD patients, showing how the disposition of anti-TNF drugs is significantly influenced by the degree of immunological activation.
Identifiants
pubmed: 30776076
pii: 5330801
doi: 10.1093/ibd/izz012
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Antibodies, Monoclonal
0
Biomarkers
0
IL10 protein, human
0
Tumor Necrosis Factor-alpha
0
Interleukin-10
130068-27-8
Types de publication
Journal Article
Multicenter Study
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1357-1366Informations de copyright
© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.