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

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.