P207 Serological Antibodies for the Prediction of Post-operative Recurrent Crohn's Disease. Results from the POCER study
A.L. Hamilton*1, M.A. Kamm2, F. Selvaraj3, F. Princen3, P. De Cruz2, E.K. Wright2, K.J. Ritchie2, E.O. Krejany1, A. Gorelik2, D. Liew2, L. Prideaux2, I.C. Lawrance2, J.M. Andrews2, P.A. Bampton2, M. Sparrow2, T.H. Florin2, P.R. Gibson2, H. Debinski2, R. Gearry2, F.A. Macrae2, R. Leong2, I. Kronborg2, G. Radford-Smith2, W. Selby2, M.J. Johnston2, R. Woods2, P.R. Elliott2, S.J. Bell2, S.J. Brown2, W.R. Connell2, P.V. Desmond2, S. Singh3
1University of Melbourne & St Vincent's Hospital, Department of Medicine, Melbourne, Australia, 2St Vincent's Hospital & University of Melbourne, Department of Gastroenterology, Melbourne, Australia, 3Prometheus Laboratories, Therapeutics & Diagnostics, San Diego, California, United States
Disease recurrence after Crohn's disease resection occurs in up to up to 80% of patients, with two thirds ultimately requiring further surgery. Although clinical risk factors help in assessing the risk of relapse, a test that identifies patients at higher risk of recurrence would be clinically valuable. We investigated the value of serological antimicrobial antibodies to predict disease recurrence after surgery in a large prospective cohort of patients.
171 patients had 525 samples tested peri-operatively, and 6, 12 and 18 months post-operatively as part of a structured study ("POCER") designed to diminish post-operative recurrence. Two-thirds of patients underwent colonoscopy at 6 months and all underwent colonoscopy at 18 months post-operatively. Serologic markers (ANCA, pANCA, ASCA IgA/IgG, anti-OmpC, anti-CBir1, anti-A4-Fla2, anti-Fla-X) were tested at each time point. Univariate analysis was performed for each (positive/negative) at all time points for endoscopic recurrence (Rutgeert's score ≥i2). Antibody titre was investigated using quartile sum score (QSS) method (range 7-28) and logistic regression analysis.
Patients with recurrence at 18 months were more likely to be positive for anti-Fla-X than those without recurrence, when measured at baseline (64% v 45%; P=0.049), 6 months (65% v 43%, P=0.021) and 18 months (53% v 33%, P=0.038) post operatively. Patients negative for anti-Fla-X at 6 months had a lower risk of recurrence at 18 months (OR 0.38, 95%CI 0.17-0.84, P=0.018), when adjusted for age, gender, disease behaviour and smoking. A negative ANCA titre at 6 months was associated with recurrence at 6 months (ANCA -ve v +ve: recurrence 87% v 13%, P=0.002). Adjusted for baseline characteristics (age, gender disease location, smoking, pANCA) the total antibody titre for all antibodies combined was not predictive of endoscopic recurrence at 6 or 18 months.
The presence of the serological antibody anti-Fla-X identifies patients at higher risk of developing early disease recurrence, while the presence of positive ANCA predicts patients at lower risk of post-operative recurrence. Fla-X is an immunogenic bacterial antigen, arising from subunits of bacterial flagella (flagellin) from Clostridium subphylum cluster XIVa. Serologic screening of patients prior to surgery may assist in selecting patients at elevated risk of post-operative recurrence. The role of Fla-X in relation to microbiota that may be linked to recurrence requires evaluation.