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

J Crohns Colitis. 2024 Apr 23;18(4):493-505. doi: 10.1093/ecco-jcc/jjad170.

Abstract

Background and aims: This study assessed whether baseline triggering receptor expressed on myeloid cells [TREM-1] whole blood gene expression predicts response to anti-tumour necrosis factor [anti-TNF] therapy in patients with ulcerative colitis [UC] or Crohn's disease [CD].

Methods: TREM-1 whole blood gene expression was analysed by RNA sequencing 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: 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], or 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: 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 inflammatory bowel disease.

Clinicaltrials.gov identifiers: NCT02065622; NCT02065570.

Keywords: Biomarkers; clinical trials.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adalimumab* / therapeutic use
  • Adult
  • Biomarkers / blood
  • Colitis, Ulcerative* / blood
  • Colitis, Ulcerative* / drug therapy
  • Colitis, Ulcerative* / genetics
  • Crohn Disease* / blood
  • Crohn Disease* / drug therapy
  • Crohn Disease* / genetics
  • Female
  • Gene Expression
  • Humans
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Remission Induction / methods
  • Treatment Outcome
  • Triggering Receptor Expressed on Myeloid Cells-1* / blood
  • Triggering Receptor Expressed on Myeloid Cells-1* / genetics

Substances

  • Triggering Receptor Expressed on Myeloid Cells-1
  • Adalimumab
  • TREM1 protein, human
  • Biomarkers

Associated data

  • ClinicalTrials.gov/NCT02065622
  • ClinicalTrials.gov/NCT02065570

Grants and funding