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  • Distinct blood protein profiles associated with the risk of short-term and mid/long-term clinical relapse in patients with Crohn’s disease stopping infliximab: when the remission state hides different types of residual disease activity

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Inflammatory bowel disease
Original research
Distinct blood protein profiles associated with the risk of short-term and mid/long-term clinical relapse in patients with Crohn’s disease stopping infliximab: when the remission state hides different types of residual disease activity
  1. Nicolas Pierre1,
  2. Vân Anh Huynh-Thu2,
  3. Thomas Marichal3,
  4. Matthieu Allez4,
  5. Yoram Bouhnik5,
  6. David Laharie6,
  7. Arnaud Bourreille7,
  8. Jean-Frédéric Colombel8,
  9. Marie-Alice Meuwis1,9,
  10. Edouard Louis1,9
  11. GETAID (Groupe d’Etude Thérapeutique des Affections Inflammatoires du tube Digestif)
  1. 1 Laboratory of Translational Gastroenterology, GIGA-institute, University of Liege, Liege, Belgium
  2. 2 Department of Electrical Engineering and Computer Science, University of Liege, Liege, Belgium
  3. 3 Laboratory of Immunophysiology, GIGA-institute, University of Liege, Liege, Belgium
  4. 4 Service d’Hépato-Gastroentérologie, Hôpital Saint Louis, APHP, Université de Paris, Paris, France
  5. 5 Service de Gastroentérologie et Assistance Nutritive, Hôpital Beaujon, Clichy, France
  6. 6 Service d’Hépato-Gastroentérologie, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
  7. 7 Institut des maladies de l’appareil digestif, Centre Hospitalier Universitaire de Nantes, Nantes, France
  8. 8 Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
  9. 9 Department of Hepato-Gastroenterology and Digestive Oncology, Liege University Hospital, Liege, Belgium
  1. Correspondence to Dr Nicolas Pierre, Laboratory of Translational Gastroenterology, GIGA-institute, University of Liege, Liege, Belgium; nicolas.pierre{at}uliege.be

Abstract

Objective Despite being in sustained and stable remission, patients with Crohn’s disease (CD) stopping anti-tumour necrosis factor α (TNFα) show a high rate of relapse (~50% within 2 years). Characterising non-invasively the biological profiles of those patients is needed to better guide the decision of anti-TNFα withdrawal.

Design Ninety-two immune-related proteins were measured by proximity extension assay in serum of patients with CD (n=102) in sustained steroid-free remission and stopping anti-TNFα (infliximab). As previously shown, a stratification based on time to clinical relapse was used to characterise the distinct biological profiles of relapsers (short-term relapsers: <6 months vs mid/long-term relapsers: >6 months). Associations between protein levels and time to clinical relapse were determined by univariable Cox model.

Results The risk (HR) of mid/long-term clinical relapse was specifically associated with a high serum level of proteins mainly expressed in lymphocytes (LAG3, SH2B3, SIT1; HR: 2.2–4.5; p<0.05), a low serum level of anti-inflammatory effectors (IL-10, HSD11B1; HR: 0.2–0.3; p<0.05) and cellular junction proteins (CDSN, CNTNAP2, CXADR, ITGA11; HR: 0.4; p<0.05). The risk of short-term clinical relapse was specifically associated with a high serum level of pro-inflammatory effectors (IL-6, IL12RB1; HR: 3.5–3.6; p<0.05) and a low or high serum level of proteins mainly expressed in antigen presenting cells (CLEC4A, CLEC4C, CLEC7A, LAMP3; HR: 0.4–4.1; p<0.05).

Conclusion We identified distinct blood protein profiles associated with the risk of short-term and mid/long-term clinical relapse in patients with CD stopping infliximab. These findings constitute an advance for the development of non-invasive biomarkers guiding the decision of anti-TNFα withdrawal.

  • Crohn's disease
  • infliximab
  • clinical decision making

Data availability statement

Data are available upon reasonable request. Data supporting the reported results (deidentified individual participant data and raw data of the PEA) can be shared upon request to the corresponding author. All the processed data are available in the supplemental tables.

https://doi.org/10.1136/gutjnl-2022-327321

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    Data availability statement

    Data are available upon reasonable request. Data supporting the reported results (deidentified individual participant data and raw data of the PEA) can be shared upon request to the corresponding author. All the processed data are available in the supplemental tables.

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    Footnotes

    • M-AM and EL contributed equally.

    • Presented at 16th Congress of European Crohn’s and Colitis Organisation, 2021.

    • Contributors M-AM, YB, DL, J-FC, MA and EL designed the study. The GETAID provided the samples and the clinical information. VAH-T performed the statistical analysis. NP analysed and interpreted the data with the help of M-AM, VAH-T, TM and EL. NP wrote the initial draft of the manuscript with the assistance of M-AM, TM, VAH-T and EL. Guarantor: NP

    • Funding Financial support was provided by internal funding from ULiège and CHU de Liège.

    • Competing interests None declared.

    • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.