Serological Markers as Predictors of Anti-TNF Response in Children with Crohn’s Disease

Yaara Lisai-Goldstein, Gili Focht, Esther Orlanski-Meyer, Dotan Yogev, Raffi Lev-Tzion, Oren Ledder, Amit Assa, Victor Manuel Navas-López, Robert N. Baldassano, Anthony Otley, Dror S. Shouval, Anne M. Griffiths, Dan Turner, Ohad Atia*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: To advance personalized medicine in pediatric Crohn’s disease (CD), we aimed to explore the utility of serological biomarkers in predicting response to anti-tumor necrosis factor (TNF). Methods: Children with CD were enrolled at initiation of anti-TNF and followed prospectively at 4 and 12 months thereafter, as well as at last follow-up. At baseline, 10 serological markers of the “PROMETHEUS® IBD sgi Diagnostic test” were measured, including pANCA, ASCA IgG and IgA, anti-CBir1, anti-OmpC, anti-A4-Fla2, anti-Fla-X, SAA, ICAM-1 and VCAM-1. The primary outcome was sustained steroid-free remission (SSFR, i.e. clinical remission without steroids at both 4 and 12 months) and the secondary outcome was primary non-response (PNR). Results: Of the 72 included children (mean age, 12.8 ± 3.1 years; median disease duration, 6.4 months [IQR 2.5–17.3]), 42 (58%) were treated with adalimumab and 30 (42%) with infliximab. PNR was noted in 20 (28%) children and failure to achieve SSFR in 36 (50%). The most common positive serological markers were SAA (86%) and ICAM-1 (82%). In univariate analyses, none of the serological markers achieved statistical significance in association with SSFR or with PNR. In multivariable analysis, positivity of ASCA IgG (OR 3.3 [95%CI 0.8–14.4]) and pANCA (OR 5.3 [95%CI 0.9–48]) were the closest to achieving significance in predicting SSFR, with fair predictive performance for the model (AUC 0.67 [95%CI 0.55–0.80]). Conclusion: The serological markers tested here have limited utility in predicting response to anti-TNF treatment. Further studies with larger sample sizes are needed to confirm the utility of ASCA IgG and pANCA.

Original languageEnglish
JournalDigestive Diseases and Sciences
DOIs
StateAccepted/In press - 2024

Bibliographical note

Publisher Copyright:
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.

Keywords

  • Anti-TNF
  • Crohn disease
  • Predictor
  • Serology

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