TY - JOUR
T1 - Serological Markers as Predictors of Anti-TNF Response in Children with Crohn’s Disease
AU - Lisai-Goldstein, Yaara
AU - Focht, Gili
AU - Orlanski-Meyer, Esther
AU - Yogev, Dotan
AU - Lev-Tzion, Raffi
AU - Ledder, Oren
AU - Assa, Amit
AU - Navas-López, Victor Manuel
AU - Baldassano, Robert N.
AU - Otley, Anthony
AU - Shouval, Dror S.
AU - Griffiths, Anne M.
AU - Turner, Dan
AU - Atia, Ohad
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - Anti-TNF
KW - Crohn disease
KW - Predictor
KW - Serology
UR - http://www.scopus.com/inward/record.url?scp=85210489904&partnerID=8YFLogxK
U2 - 10.1007/s10620-024-08732-y
DO - 10.1007/s10620-024-08732-y
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C2 - 39604667
AN - SCOPUS:85210489904
SN - 0163-2116
JO - Digestive Diseases and Sciences
JF - Digestive Diseases and Sciences
ER -