DOP052. Active smoking, and pre-operative anti-flagellin Fla2 and pANCA antibodies may predict postoperative Crohn's disease recurrence: results from a prospective mono-centric trial
M. Noben1, A. de Buck van Overstraeten2, S. Lockton3, G. De Hertogh4, F. Princen3, A. Wolthuis2, G. Van Assche1, S. Vermeire1, S. Singh3, A. D'Hoore2, M. Ferrante1, 1University Hospitals Leuven, Department of Gastroenterology, Leuven, Belgium, 2University Hospitals Leuven, Department of Abdominal Surgery, Leuven, Belgium, 3Prometheus Laboratories, Department of Research and Development, San Diego, United States, 4University Hospitals Leuven, Department of Pathology, Leuven, Belgium
Preventing postoperative endoscopic (ER) and clinical recurrence (CR) remains a challenging issue in patients with Crohn's disease (CD) undergoing an intestinal resection. Several clinical and histological risk factors have been identified, and may guide postoperative prophylactic CD therapy. We evaluated if pre-operative serological markers could strengthen prediction of postoperative ER and CR.
The study population consisted of 100 consecutive patients (41 males, 27 active smokers, median age 41.7 years) undergoing an ileal resection with ileocolonic anastomosis for refractory CD, in whom a serum sample was collected ≤1 week prior to surgery. All patients underwent a postoperative endoscopic evaluation at 6 months. The primary endpoint, ER, was defined as a postoperative endoscopic recurrence score of i3 or i4. Secondary endpoints included time to clinical recurrence. Sera were analysed blindly at Prometheus laboratories for the expression of ASCA IgA and IgG antibodies, three different anti-flagellin antibodies (CBir1, Fla2 and FlaX), OmpC, and pANCA. The Q3 value of each individual marker in this dataset was defined as the cut-off point. Predictors of both ER and CR in univariate analyses were included in the binary logistic and Cox regression analysis.
Twenty-five patients developed ER at 6 months. Fla2 > 66 EU [Odds ratio 3.0 (95% confidence interval 1.1–8.7), p = 0.037], and active smoking [3.1 (1.1–8.8), p = 0.029], were independently associated with ER. During a median follow-up of 23.6 months, 29 patients developed a CR, with Fla2 > 66 EU [2.2 (1.0–4.6), p = 0.041], pANCA positivity [2.5 (1.2–5.4), p = 0.016], and active smoking [2.6 (1.2–5.5), p = 0.011], as independent risk factors. A cumulative risk score was developed by combining 3 risk factors (Fla2 > 66 EU, pANCA positivity, and active smoking). Based on this cumulative risk score, we could observe a significant and gradual increased risk of both ER (Figure 1, linear-by-linear p < 0.001) and CR (Figure 2, LogRank p < 0.001).
Pre-operative serological markers, including anti-flagellin Fla2 antibodies, were independently associated with postoperative ER and CR. We identified a risk panel of clinical and serological markers which may guide postoperative prophylactic therapy. Validation of these results in an independent cohort is warranted.