The Citrullinated and MMP-degraded Vimentin Biomarker (VICM) Predicts Early Response to Anti-TNFα Treatment in Crohn's Disease

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  • Joachim H Mortensen, Herlev University Hospital, Herlev Ringvej 75, 2730 Herlev, Denmark.
  • ,
  • Wouter T van Haaften, Department of Pharmaceutical Technology and Biopharmacy
  • ,
  • Morten A Karsdal, Herlev University Hospital, Herlev Ringvej 75, 2730 Herlev, Denmark.
  • ,
  • Anne-Christine Bay-Jensen, Herlev University Hospital, Herlev Ringvej 75, 2730 Herlev, Denmark.
  • ,
  • Peter Olinga, Department of Pharmaceutical Technology and Biopharmacy
  • ,
  • Henning Grønbæk
  • Christian L Hvas
  • Tina Manon-Jensen, Herlev University Hospital, Herlev Ringvej 75, 2730 Herlev, Denmark.
  • ,
  • Gerard Dijkstra, Department of Pharmaceutical Technology and Biopharmacy
  • ,
  • Anders Dige

BACKGROUND: In Crohn's disease (CD), 10% to 40% of patients do not respond to anti-tumor necrosis factor-α (TNFα) treatment. Currently, there are no biomarkers with adequate sensitivity to separate responders from nonresponders at an early stage.

AIM: The aim of this study was to investigated whether early changes in the VICM (citrullinated and matrix metalloproteinase-degraded vimentin) biomarker were associated with response to anti-TNFα treatment in patients with CD.

METHODS: Serum VICM levels were measured by ELISA in 2 independent cohorts of CD patients (n=42) treated with anti-TNFα (infliximab or adalimumab). Response was determined by achieving clinical remission (Harvey Bradshaw Index<5).

RESULTS: Compared with baseline, VICM serum levels were reduced by anti-TNFα in the infliximab cohort (week 6 and 14) and in the adalimumab cohort (week 8). VICM was lower in the responders compared with the nonresponders [infliximab: week 6, P<0.05; area under the curve (AUC)=0.90; adalimumab: week 1, P<0.01 (AUC=0.91), and week 8, P<0.05 (AUC=0.86)], and were able to predict response to treatment after 1 week of treatment with an odds ratio of 42.5.

CONCLUSIONS: The VICM biomarker was time dependently reduced in CD patients responding to anti-TNFα treatment. We suggest that VICM may be used as a marker for monitoring early response to anti-TNFα in patients with CD.

OriginalsprogEngelsk
TidsskriftJournal of Clinical Gastroenterology
ISSN0192-0790
DOI
StatusE-pub ahead of print - 14 apr. 2020

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