P243 The association between serological markers ASCA and ANCA and response to induction treatment in therapy-naïve children with inflammatory bowel disease: an international prospective study

Klomberg, R.(1)*;Kaper, D.(1);Barendregt, D.(2);Vuijk, S.(1);Schreurs, M.(3);Charrout, M.(4);Ruemmele, F.(5);Kemos, P.(6);Croft, N.(6);Samsom, J.(2);de Ridder, L.(1);

(1)Erasmus MC - Sophia Children's Hospital, Paediatric Gastroenterology, Rotterdam, The Netherlands;(2)Erasmus MC, Department of Medical Immunology, Rotterdam, The Netherlands;(3)Erasmus MC, Laboratory of Medical Immunology, Rotterdam, The Netherlands;(4)Delf University of Technology, Delft Bioinformatics Lab, Delft, The Netherlands;(5)Necker Hospital for Sick Children, Paediatric Gastroenterology, Paris, France;(6)Queen Mary University of London, Pediatric Gastroenterology- Center for Immunobiology- Blizard Institute, London, United Kingdom; PIBD-SETQuality consortium

Background

Pediatric-onset inflammatory bowel disease (PIBD) is a chronic disease with a heterogeneous spectrum. A better understanding of predicting factors for therapy response could improve personalized care and reduce complications. Possible predicting factors of a complicated disease behavior in PIBD are the presence of anti-Saccharomyces cerevisiae (ASCA) and antineutrophil cytoplasmic antibodies (ANCA) in the serum, though existing evidence is inconclusive. We aimed to investigate the association of serological markers ASCA and ANCA with short-term therapy response at 3 and 6 months in PIBD patients.

Methods

As part of the multicenter prospective observational PIBD-SETQuality study, blood from therapy-naïve PIBD patients (n=162) with a minimum follow-up of 6 months was analyzed for 3 serological markers (ASCA IgA, ASCA IgG and/or ANCA) at diagnosis. Outcome measures included clinical remission and biochemical remission (remission with CRP <0.5 mg/dl or fecal calprotectin < 300 mcg/g), small or moderate improvement after induction treatment, and therapy use at 3 and 6 months. To evaluate effect of ASCA titers, serology sum scores (SSS) were obtained by combining results of ANCA status and scores of ASCA titer quartiles, and compared between outcomes.

Results

ASCA IgA and IgG were more prevalent in Crohn’s disease (CD) patients [47% vs. 2% for IgA; 75% vs. 5% for IgG, p<0.001] and ANCA in ulcerative colitis/inflammatory bowel disease unclassified (UC/IBD-U) [43% vs. 11%, p<0.001] patients. ASCA IgA and IgG were not associated with markers of disease activity (albumin, CRP, wPCDAI) at diagnosis in children with CD, but ASCA IgG positivity was more prevalent in patients with an ileocolonic distribution (L3 57%, L2 6%, L1 37%, p=0.024). ANCA positivity was not associated with any disease characteristic at diagnosis. No association was found between clinical or biochemical remission status at 3 and 6 months and ASCA and ANCA positivity. Additionally, no association was found between ASCA and ANCA positivity and small or moderate response to induction therapy at 3 and 6 months. ASCA IgG positive patients had higher rates of anti-TNF use at 6 months compared to ASCA IgG negative patients [84% vs. 50%, p=0.041]. Patients with higher SSS did not tend to have poorer outcomes at 3 and 6 months compared to patients with lower SSS.

Conclusion

While serological markers ASCA and ANCA may provide a way to better differentiate between CD and UC/IBD-U in PIBD, this study did not find any association between ASCA and ANCA and short-term therapy response. ASCA IgG patients were more likely to have used anti-TNF at 6 months, possibly reflecting more severe disease.