Baseline expression of immune gene modules in blood is associated with primary response to anti-TNF therapy in Crohn's disease patients.
Anti-TNF
Crohn’s disease
transcriptomic biomarkers
Journal
Journal of Crohn's & colitis
ISSN: 1876-4479
Titre abrégé: J Crohns Colitis
Pays: England
ID NLM: 101318676
Informations de publication
Date de publication:
30 Sep 2023
30 Sep 2023
Historique:
received:
06
06
2023
medline:
1
10
2023
pubmed:
1
10
2023
entrez:
30
9
2023
Statut:
aheadofprint
Résumé
Anti-TNF therapy is widely used for treatment of inflammatory bowel disease, yet many patients are primary non-responders, failing to respond to induction therapy. We aimed to identify blood gene expression differences between primary responders and primary non-responders to anti-TNF monoclonal antibodies (infliximab and adalimumab); and to predict response status from blood gene expression and clinical data. The Personalised Anti-TNF Therapy in Crohn's Disease (PANTS) study is a UK-wide prospective observational cohort study of anti-TNF therapy outcome in anti-TNF naive Crohn's disease patients (ClinicalTrials.gov identifier: NCT03088449). Blood gene expression in 324 unique patients was measured by RNA-seq at baseline (week 0), and at weeks 14, 30, and 54 after treatment initiation (total sample size = 814). After adjusting for clinical covariates and estimated blood cell composition, baseline expression of major histocompatibility complex, antigen presentation, myeloid cell enriched receptor, and other innate immune gene modules was significantly higher in anti-TNF responders versus non-responders. Expression changes from baseline to week 14 were generally of consistent direction but greater magnitude (i.e. amplified) in responders, however interferon-related genes were upregulated uniquely in non-responders. Expression differences between responders and non-responders observed at week 14 were maintained at week 30 and week 54. Prediction of response status from baseline clinical data, cell composition, and module expression was poor. Baseline gene module expression was associated with primary response to anti-TNF therapy in PANTS patients. However, these baseline expression differences did not predict response with sufficient sensitivity for clinical use.
Sections du résumé
BACKGROUND AND AIMS
OBJECTIVE
Anti-TNF therapy is widely used for treatment of inflammatory bowel disease, yet many patients are primary non-responders, failing to respond to induction therapy. We aimed to identify blood gene expression differences between primary responders and primary non-responders to anti-TNF monoclonal antibodies (infliximab and adalimumab); and to predict response status from blood gene expression and clinical data.
METHODS
METHODS
The Personalised Anti-TNF Therapy in Crohn's Disease (PANTS) study is a UK-wide prospective observational cohort study of anti-TNF therapy outcome in anti-TNF naive Crohn's disease patients (ClinicalTrials.gov identifier: NCT03088449). Blood gene expression in 324 unique patients was measured by RNA-seq at baseline (week 0), and at weeks 14, 30, and 54 after treatment initiation (total sample size = 814).
RESULTS
RESULTS
After adjusting for clinical covariates and estimated blood cell composition, baseline expression of major histocompatibility complex, antigen presentation, myeloid cell enriched receptor, and other innate immune gene modules was significantly higher in anti-TNF responders versus non-responders. Expression changes from baseline to week 14 were generally of consistent direction but greater magnitude (i.e. amplified) in responders, however interferon-related genes were upregulated uniquely in non-responders. Expression differences between responders and non-responders observed at week 14 were maintained at week 30 and week 54. Prediction of response status from baseline clinical data, cell composition, and module expression was poor.
CONCLUSIONS
CONCLUSIONS
Baseline gene module expression was associated with primary response to anti-TNF therapy in PANTS patients. However, these baseline expression differences did not predict response with sufficient sensitivity for clinical use.
Identifiants
pubmed: 37776235
pii: 7287040
doi: 10.1093/ecco-jcc/jjad166
pii:
doi:
Banques de données
ClinicalTrials.gov
['NCT03088449']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.