Baseline TREM-1 Whole Blood Gene Expression Does Not Predict Response to Adalimumab Treatment in Patients with Ulcerative Colitis or Crohn's Disease in the SERENE Studies.

biomarkers clinical trials

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:
06 Oct 2023
Historique:
received: 31 03 2023
medline: 6 10 2023
pubmed: 6 10 2023
entrez: 6 10 2023
Statut: aheadofprint

Résumé

This study assessed whether baseline triggering receptor expressed on myeloid cells [TREM-1] whole blood gene expression predicts response to anti-TNF therapy in patients with UC or CD. TREM-1 whole blood gene expression was analysed by RNA sequencing [RNA-seq] in patients with moderately to severely active UC or CD treated with adalimumab in the Phase 3 SERENE-UC and SERENE-CD clinical trials. The predictive value of baseline TREM-1 expression was evaluated and compared according to endoscopic and clinical response vs non-response, and remission vs non-remission, at Weeks 8 and 52 [SERENE-UC], and Weeks 12 and 56 [SERENE-CD]. TREM-1 expression was analysed in 95 and 106 patients with UC and CD, respectively, receiving standard-dose adalimumab induction treatment. In SERENE-UC, baseline TREM-1 expression was not predictive of endoscopic response [p=0.48], endoscopic remission [p=0.53], clinical response [p=0.58] or clinical remission [p=0.79] at Week 8, or clinical response [p=0.60] at Week 52. However, an association was observed with endoscopic response [p=0.01], endoscopic remission [p=0.048], and clinical remission [p=0.04997] at Week 52. For SERENE-CD, baseline TREM-1 expression was not predictive of endoscopic response [p=0.56], endoscopic remission [p=0.33], clinical response [p=0.07], clinical remission [p=0.65] at Week 12, or endoscopic response [p=0.61], endoscopic remission [p=0.51], clinical response [p=0.62] or clinical remission [p=0.97] at Week 56. Baseline TREM-1 gene expression did not uniformly predict adalimumab response in SERENE clinical trials. Further research is needed to identify potential blood-based biomarkers predictive of response to anti-TNF therapy in patients with IBD.

Sections du résumé

BACKGROUND AND AIMS OBJECTIVE
This study assessed whether baseline triggering receptor expressed on myeloid cells [TREM-1] whole blood gene expression predicts response to anti-TNF therapy in patients with UC or CD.
METHODS METHODS
TREM-1 whole blood gene expression was analysed by RNA sequencing [RNA-seq] in patients with moderately to severely active UC or CD treated with adalimumab in the Phase 3 SERENE-UC and SERENE-CD clinical trials. The predictive value of baseline TREM-1 expression was evaluated and compared according to endoscopic and clinical response vs non-response, and remission vs non-remission, at Weeks 8 and 52 [SERENE-UC], and Weeks 12 and 56 [SERENE-CD].
RESULTS RESULTS
TREM-1 expression was analysed in 95 and 106 patients with UC and CD, respectively, receiving standard-dose adalimumab induction treatment. In SERENE-UC, baseline TREM-1 expression was not predictive of endoscopic response [p=0.48], endoscopic remission [p=0.53], clinical response [p=0.58] or clinical remission [p=0.79] at Week 8, or clinical response [p=0.60] at Week 52. However, an association was observed with endoscopic response [p=0.01], endoscopic remission [p=0.048], and clinical remission [p=0.04997] at Week 52. For SERENE-CD, baseline TREM-1 expression was not predictive of endoscopic response [p=0.56], endoscopic remission [p=0.33], clinical response [p=0.07], clinical remission [p=0.65] at Week 12, or endoscopic response [p=0.61], endoscopic remission [p=0.51], clinical response [p=0.62] or clinical remission [p=0.97] at Week 56.
CONCLUSIONS CONCLUSIONS
Baseline TREM-1 gene expression did not uniformly predict adalimumab response in SERENE clinical trials. Further research is needed to identify potential blood-based biomarkers predictive of response to anti-TNF therapy in patients with IBD.

Identifiants

pubmed: 37801628
pii: 7293415
doi: 10.1093/ecco-jcc/jjad170
pii:
doi:

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.

Auteurs

Bram Verstockt (B)

Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.
Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.

Valerie Pivorunas (V)

Precision Medicine Immunology, AbbVie Bioresearch Centre, Worcester, MA, USA.

Naim Al Mahi (NA)

Genomic Research Center, AbbVie, North Chicago, IL, USA.

Nizar Smaoui (N)

Genomic Research Center, AbbVie, North Chicago, IL, USA.

Heath Guay (H)

Precision Medicine Immunology, AbbVie Bioresearch Centre, Worcester, MA, USA.

Nicholas A Kennedy (NA)

Department of Gastroenterology, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK.

James R Goodhand (JR)

Department of Gastroenterology, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK.

Simeng Lin (S)

Department of Gastroenterology, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK.

Benjamin Y H Bai (BYH)

Genomics of Inflammation and Immunity Group, Wellcome Sanger Institute, Hinxton, UK.

Stephen B Hanauer (SB)

Department of Medicine, Northwestern University Feinberg School of Medicine, Evanston, IL, USA.

Marc Ferrante (M)

Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.
Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.

Julian Panés (J)

Hospital Clinic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Catalonia, Spain.

Séverine Vermeire (S)

Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.
Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.

Classifications MeSH