P431 Serology panel for prediction relapse after discontinuation of infliximab in patients with Crohn's disease achieving clinical remission
K. Papamichail*1, 2, K. Claes1, M. de Bruyn1, S. Hauenstein3, F. Princen3, S. Singh3, G.A. Van Assche1, P.J. Rutgeerts1, S. Vermeire1, M. Ferrante1
1KU Leuven, Department of Clinical and Experimental Medicine, Translational Research Center for GastroIntestinal Disorders (TARGID), Leuven, Belgium, 2Evaggelismos Hospital, Gastroenterology Clinic, Athens, Greece, 3Prometheus Laboratories, Therapeutics & Diagnostics, San Diego, California, United States
Stopping rules for anti-tumor necrosis factor (TNF) therapy are urgently needed. The identification of predictive markers identifying patients at low or high risk for relapse after stopping is therefore warranted. There are limited data concerning the role of non-invasive, serological factors as predictors of relapse after anti-TNF cessation in patients with Crohn's disease (CD). We investigated whether a novel serology panel for assessment of wound healing and repair can predict relapse after infliximab (IFX) cessation for clinical remission in patients with CD.
This was an observational, retrospective, single-center study. From an electronic database we identified 100 CD patients (57 luminal CD, 40 male, median age at diagnosis 25 years) who discontinued IFX for clinical remission. The majority of patients (n=84) continued on immunomodulators. Relapse was defined as the need to re-introduce medical therapy or surgery. The serology panel included serum TNFα, amphiregulin (AREG), epiregulin (EREG), heparin-binding EGF-like growth factor (HBEGF), hepatocyte growth factor (HGF), heregulin beta EGF domain (HRGB), betacellulin (BTC), epidermal growth factor (EGF), and transforming growth factor alpha (TNFα). These markers were determined in samples taken at the time of IFX discontinuation by Prometheus Laboratories (San Diego, CA). A test was considered positive if the titers were higher than the Q3 of the samples measurements: [TNFα (>12 μg/ml), AREG (>20 U/ml), EREG (>243 U/ml), HBEGF (>12 U/ml), HGF (>74 U/ml), HRGB (>33 U/ml), BTC (>235 U/ml), EGF (>88 U/ml), TNFα (>7 U/ml)].
During a median (IQR) follow up of 9.7 (8.0-11.5) years, 48 out of 100 patients relapsed. A receiver operating characteristic (ROC) analysis did not identify predictive cut-off values for relapse after IFX discontinuation for any of the investigated serological markers. Univariate (Log-Rank) and multiple COX regression analysis revealed borderline significance for positive AREG in predicting relapse (p=0.066 and 0.068 respectively). However, multiple COX regression analysis for a sub-group of patients treated mainly for luminal disease, identified positive AREG as an independent factor predicting relapse after IFX cessation [n=34, p=0.008, HR: 8.1 (95%CI: 1.7-38.1), SN: 80%, SP: 52%, PPV: 22%, NPV: 94%].
Positive amphiregulin titers may be associated with relapse in patients who discontinue IFX for clinical remission. AREG is a member of the epidermal growth factor family which is highly expressed only in the active inflamed and not in the normal mucosa of CD patients.1 Our results warrant further study of the role of serum AREG in mucosal healing and repair in IBD.
 Nishimura T, et al., (2008), Amphiregulin and epiregulin expression in neoplastic and inflammatory lesions in the colon., Oncol Rep