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

Bram Verstockt; Valerie Pivorunas; Naim Al Mahi; Nizar Smaoui; Heath Guay; Nicholas A. Kennedy; James R. Goodhand; Simeng Lin; Benjamin Y.H. Bai; Stephen B. Hanauer; Marc Ferrante; Julian Panés; Séverine Vermeire

doi:10.1093/ecco-jcc/jjad170

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

Bram Verstockt^*, Valerie Pivorunas, Naim Al Mahi, Nizar Smaoui, Heath Guay, Nicholas A. Kennedy, James R. Goodhand, Simeng Lin, Benjamin Y.H. Bai, Stephen B. Hanauer, Marc Ferrante, Julian Panés, Séverine Vermeire

^*Corresponding author for this work

Medicine, Gastroenterology Division

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Pages (from-to)	493-505
Number of pages	13
Journal	Journal of Crohn's and Colitis
Volume	18
Issue number	4
DOIs	https://doi.org/10.1093/ecco-jcc/jjad170
State	Published - Apr 1 2024

Funding

This work was supported by AbbVie, who funded this study and participated in the study design, research, analysis, data collection, interpretation of data, and review and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship.

Keywords

Biomarkers
clinical trials

ASJC Scopus subject areas

General Medicine

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10.1093/ecco-jcc/jjad170

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Verstockt, B., Pivorunas, V., Mahi, N. A., Smaoui, N., Guay, H., Kennedy, N. A., Goodhand, J. R., Lin, S., Bai, B. Y. H., Hanauer, S. B., Ferrante, M., Panés, J., & Vermeire, S. (2024). 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. Journal of Crohn's and Colitis, 18(4), 493-505. https://doi.org/10.1093/ecco-jcc/jjad170

@article{54a601d163284851b93bc633c272fa55,

title = "Baseline TREM-1 Whole Blood Gene Expression Does Not Predict Response to Adalimumab Treatment in Patients with Ulcerative Colitis or Crohn{\textquoteright}s Disease in the SERENE Studies",

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{\textquoteright}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.",

keywords = "Biomarkers, clinical trials",

author = "Bram Verstockt and Valerie Pivorunas and Mahi, {Naim Al} and Nizar Smaoui and Heath Guay and Kennedy, {Nicholas A.} and Goodhand, {James R.} and Simeng Lin and Bai, {Benjamin Y.H.} and Hanauer, {Stephen B.} and Marc Ferrante and Julian Pan{\'e}s and S{\'e}verine Vermeire",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn{\textquoteright}s and Colitis Organisation.",

year = "2024",

month = apr,

day = "1",

doi = "10.1093/ecco-jcc/jjad170",

language = "English (US)",

volume = "18",

pages = "493--505",

journal = "Journal of Crohn's and Colitis",

issn = "1873-9946",

publisher = "Elsevier",

number = "4",

}

Verstockt, B, Pivorunas, V, Mahi, NA, Smaoui, N, Guay, H, Kennedy, NA, Goodhand, JR, Lin, S, Bai, BYH, Hanauer, SB, Ferrante, M, Panés, J & Vermeire, S 2024, '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', Journal of Crohn's and Colitis, vol. 18, no. 4, pp. 493-505. https://doi.org/10.1093/ecco-jcc/jjad170

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. / Verstockt, Bram; Pivorunas, Valerie; Mahi, Naim Al et al.
In: Journal of Crohn's and Colitis, Vol. 18, No. 4, 01.04.2024, p. 493-505.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - 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

AU - Verstockt, Bram

AU - Pivorunas, Valerie

AU - Mahi, Naim Al

AU - Smaoui, Nizar

AU - Guay, Heath

AU - Kennedy, Nicholas A.

AU - Goodhand, James R.

AU - Lin, Simeng

AU - Bai, Benjamin Y.H.

AU - Hanauer, Stephen B.

AU - Ferrante, Marc

AU - Panés, Julian

AU - Vermeire, Séverine

PY - 2024/4/1

Y1 - 2024/4/1

N2 - 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.

AB - 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.

KW - Biomarkers

KW - clinical trials

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UR - http://www.scopus.com/inward/citedby.url?scp=85191105918&partnerID=8YFLogxK

U2 - 10.1093/ecco-jcc/jjad170

DO - 10.1093/ecco-jcc/jjad170

M3 - Article

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AN - SCOPUS:85191105918

SN - 1873-9946

VL - 18

SP - 493

EP - 505

JO - Journal of Crohn's and Colitis

JF - Journal of Crohn's and Colitis

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ER -

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

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