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External validation of serum biomarkers predicting short-term and mid/long-term relapse in patients with Crohn’s disease stopping infliximab

Pierre, Nicolas ; Huynh-Thu, Vân Anh ; Baiwir, Dominique ; Mazzucchelli, Gabriel ; Fléron, Maximilien ; Trzpiot, Lisette ; Eppe, Gauthier ; De Pauw, Edwin ; Laharie, David and Satsangi, Jack , et al. (2024) In Gut 73. p.1965-1973
Abstract

Objective In patients with Crohn’s disease (CD) on combination therapy (infliximab and immunosuppressant) and stopping infliximab (cohort from the study of infliximab diSconTinuation in CrOhn’s disease patients in stable Remission on combined therapy with Immunosuppressors (STORI)), the risk of short-term (≤6 months) and mid/long-term relapse (>6 months) was associated with distinct blood protein profiles. Our aim was to test the external validity of this finding in the SPARE cohort (A proSpective Randomized Controlled Trial comParing infliximAb-antimetabolites Combination Therapy to Anti-metabolites monotheRapy and Infliximab monothErapy in Crohn’s Disease Patients in Sustained Steroid-free Remission on Combination Therapy). Design... (More)

Objective In patients with Crohn’s disease (CD) on combination therapy (infliximab and immunosuppressant) and stopping infliximab (cohort from the study of infliximab diSconTinuation in CrOhn’s disease patients in stable Remission on combined therapy with Immunosuppressors (STORI)), the risk of short-term (≤6 months) and mid/long-term relapse (>6 months) was associated with distinct blood protein profiles. Our aim was to test the external validity of this finding in the SPARE cohort (A proSpective Randomized Controlled Trial comParing infliximAb-antimetabolites Combination Therapy to Anti-metabolites monotheRapy and Infliximab monothErapy in Crohn’s Disease Patients in Sustained Steroid-free Remission on Combination Therapy). Design In SPARE, patients with CD in sustained steroid-free clinical remission and on combination therapy were randomly allocated to three arms: continuing combination therapy, stopping infliximab or stopping immunosuppressant. In the baseline serum of the STORI and SPARE (arm stopping infliximab) cohorts, we studied 202 immune-related proteins. The proteins associated with time to relapse (univariable Cox model) were compared between STORI and SPARE. The discriminative ability of biomarkers (individually and combined in pairs) was evaluated by the c-statistic (concordance analysis) which was compared with C-reactive protein (CRP), faecal calprotectin and a previously validated model (CEASE). Results In STORI and SPARE, distinct blood protein profiles were associated with the risk of short-term (eg, high level: CRP, haptoglobin, interleukin-6, C-type lectin domain family 4 member C) and mid/long-term relapse (eg, low level: Fms-related tyrosine kinase 3 ligand, kallistatin, fibroblast growth factor 2). At external validation, the top 10 biomarker pairs showed a higher c-statistic than the CEASE model, CRP and faecal calprotectin in predicting short-term (0.76–0.80 vs 0.74 vs 0.71 vs 0.69, respectively) and mid/long-term relapse (0.66–0.68 vs 0.61 vs 0.52 vs 0.59, respectively). Conclusion In patients with CD stopping infliximab, we confirm that the risk of short-term and mid/long-term relapse is associated with distinct blood protein profiles showing the potential to guide infliximab withdrawal.

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publishing date
type
Contribution to journal
publication status
published
subject
in
Gut
volume
73
pages
1965 - 1973
publisher
BMJ Publishing Group
external identifiers
  • pmid:39134391
  • scopus:85204199683
ISSN
0017-5749
DOI
10.1136/gutjnl-2024-332648
language
English
LU publication?
yes
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Publisher Copyright: © Author(s) (or their employer(s)) 2024.
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b9016bea-6fb2-496e-aaf0-071e1dd78325
date added to LUP
2024-10-29 11:13:09
date last changed
2025-07-09 09:24:19
@article{b9016bea-6fb2-496e-aaf0-071e1dd78325,
  abstract     = {{<p>Objective In patients with Crohn’s disease (CD) on combination therapy (infliximab and immunosuppressant) and stopping infliximab (cohort from the study of infliximab diSconTinuation in CrOhn’s disease patients in stable Remission on combined therapy with Immunosuppressors (STORI)), the risk of short-term (≤6 months) and mid/long-term relapse (&gt;6 months) was associated with distinct blood protein profiles. Our aim was to test the external validity of this finding in the SPARE cohort (A proSpective Randomized Controlled Trial comParing infliximAb-antimetabolites Combination Therapy to Anti-metabolites monotheRapy and Infliximab monothErapy in Crohn’s Disease Patients in Sustained Steroid-free Remission on Combination Therapy). Design In SPARE, patients with CD in sustained steroid-free clinical remission and on combination therapy were randomly allocated to three arms: continuing combination therapy, stopping infliximab or stopping immunosuppressant. In the baseline serum of the STORI and SPARE (arm stopping infliximab) cohorts, we studied 202 immune-related proteins. The proteins associated with time to relapse (univariable Cox model) were compared between STORI and SPARE. The discriminative ability of biomarkers (individually and combined in pairs) was evaluated by the c-statistic (concordance analysis) which was compared with C-reactive protein (CRP), faecal calprotectin and a previously validated model (CEASE). Results In STORI and SPARE, distinct blood protein profiles were associated with the risk of short-term (eg, high level: CRP, haptoglobin, interleukin-6, C-type lectin domain family 4 member C) and mid/long-term relapse (eg, low level: Fms-related tyrosine kinase 3 ligand, kallistatin, fibroblast growth factor 2). At external validation, the top 10 biomarker pairs showed a higher c-statistic than the CEASE model, CRP and faecal calprotectin in predicting short-term (0.76–0.80 vs 0.74 vs 0.71 vs 0.69, respectively) and mid/long-term relapse (0.66–0.68 vs 0.61 vs 0.52 vs 0.59, respectively). Conclusion In patients with CD stopping infliximab, we confirm that the risk of short-term and mid/long-term relapse is associated with distinct blood protein profiles showing the potential to guide infliximab withdrawal.</p>}},
  author       = {{Pierre, Nicolas and Huynh-Thu, Vân Anh and Baiwir, Dominique and Mazzucchelli, Gabriel and Fléron, Maximilien and Trzpiot, Lisette and Eppe, Gauthier and De Pauw, Edwin and Laharie, David and Satsangi, Jack and Bossuyt, Peter and Vuitton, Lucine and Vieujean, Sophie and Colombel, Jean Frédéric and Meuwis, Marie Alice and Louis, E.}},
  issn         = {{0017-5749}},
  language     = {{eng}},
  pages        = {{1965--1973}},
  publisher    = {{BMJ Publishing Group}},
  series       = {{Gut}},
  title        = {{External validation of serum biomarkers predicting short-term and mid/long-term relapse in patients with Crohn’s disease stopping infliximab}},
  url          = {{http://dx.doi.org/10.1136/gutjnl-2024-332648}},
  doi          = {{10.1136/gutjnl-2024-332648}},
  volume       = {{73}},
  year         = {{2024}},
}