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Serological Markers as Predictors of Anti-TNF Response in Children with Crohn's Disease
Yaara Lisai-Goldstein1, Gili Focht1, Esther Orlanski-Meyer1
1Juliet Keidan Institute of Pediatric Gastroenterology Hepatology and Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Eisenberg R&D Authority, P.O. Box 3235, 9103102, Jerusalem, Israel.
Insights
Serological biomarkers have limited utility in predicting treatment response for pediatric Crohn's disease patients receiving anti-tumor necrosis factor (TNF) therapy. Further research is needed to validate potential predictors like ASCA IgG and pANCA.
Area of Science:
- Pediatric Gastroenterology
- Immunology
- Personalized Medicine
Background:
- Pediatric Crohn's disease (CD) management requires personalized approaches.
- Predicting response to anti-tumor necrosis factor (TNF) therapy is crucial for optimizing treatment.
Purpose of the Study:
- To evaluate the effectiveness of serological biomarkers in predicting treatment response in pediatric CD patients undergoing anti-TNF therapy.
Main Methods:
- A prospective study of 72 children with CD initiating anti-TNF therapy.
- Measurement of 10 serological markers at baseline using the PROMETHEUS® IBD sgi Diagnostic test.
- Assessment of sustained steroid-free remission (SSFR) and primary non-response (PNR) at 4 and 12 months.
Main Results:
- No significant association was found between tested serological markers and SSFR or PNR in univariate analyses.
- ASCA IgG and pANCA showed the closest association with predicting SSFR in multivariable analysis (AUC 0.67).
- The most frequent markers were SAA (86%) and ICAM-1 (82%).
Conclusions:
- Current serological markers have limited predictive value for anti-TNF treatment response in pediatric CD.
- Larger studies are necessary to confirm the potential utility of ASCA IgG and pANCA.
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.
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