OC.02.6 IDENTIFICATION OF A CUT-OFF FOR PERSISTENT ANTI-INFLIXIMAB ANTIBODIES AS A PREDICTOR OF RESPONSE TO INFLIXIMAB MONOTHERAPY

Abstracts of the 22nd National Congress of Digestive Diseases / Digestive and Liver Disease 48S2 (2016) e67–e231

of markers of platelets activation correlate with the incidence of CAD in IBD. Our results may also provide the rationale for targeting platelet activation to improve both IBD activity and cardiovascular risk.

OC.02.5 EXPERIMENTAL COMPARISON BETWEEN TWO MARKERS OF INTESTINAL INFLAMMATION, HMGB1 AND FECAL CALPROTECTIN, IN INFLAMMATORY BOWEL DISEASES Barberio B.*1, D’Inca’ R.1, Stronati L.2, Vitali R.2, Palone F.2, Cucchiara S.3, Sturniolo G.C.1 1 Azienda Ospedaliera di Padova, Padova, Italy, 2Dipartimento di Radiobiologia e Salute dell’Uomo, ENEA, Roma, Italy, 3Dipartimento di Gastroenterologia ed Epatologia Pediatrica, Azienda Policlinico Umberto I, Roma, Italy

Background and aim: In inflammatory bowel diseases (IBD), the fecal marker currently mostly used is calprotectin. Recently, HMGB1 has been proposed as a new surrogate marker of intestinal inflammation. This is a non-histone chromatin protein with an architectural function, which, after proinflammatory stimuli (TNFalpha, IL-1, IFN-gamma), is secreted by immune cells. We evaluated the correlation between fecal levels of HMGB1 and disease severity (as assessed by endoscopic indexes), and compared the results with those obtained with the measurement of fecal calprotectin. Moreover, we assessed the specificity of this marker for IBD by analyzing samples of non-IBD patients. Material and methods: We recruited three groups of patients: IBD patients (of which 20 with Crohn’s Disease and 25 with Ulcerative Colitis); a control group consisting of 15 irritable bowel disease (IBS) patients; a control group consisting of 7 patients with intestinal inflammation of non-IBD type (3 infectious colitis and 4 diverticulitis). We collected two fecal samples for each subject: calprotectin was analyzed by ELISA, HMGB1 by the Western blot technique. Results: Both calprotectin and HMGB1were significantly increased in IBD compared to IBS patients. In non-IBD patients, calprotectin was statistically more elevated than in IBS controls. Calprotectin more effectively than HMGB1 correlated with endoscopic indices of Crohn’s Disease with significant discrimination between mild IBD vs IBS (p <0.01), and mild vs moderate IBD (p<0.05). In Ulcerative Colitis, HMGB1 discriminated mild disease from IBS controls (p <0.01), and moderate vs severe disease activity (p <0.01). Both markers showed satisfactory sensitivity and specificity by the ROC curves: calprotectin showed sensitivity of 85% and specificity of 86.7% in Crohn’s disease, while in Ulcerative Colitis sensitivity was 68% and specificity 87.6%; on the other hand, HMGB1 had 75% sensitivity and 73.3% specificity in Crohn’s disease, and 80% sensitivity and 73% specificity in Ulcerative Colitis. In IBD calprotectin had 75.5% sensitivity and 86.7% specificity, while HMGB1 showed 77.7% sensitivity and 73.4% specificity. In non-IBD patients, calprotectin showed high sensitivity and specificity (85.7% and 93.7% respectively), while HMGB1 had 57.14% sensitivity and 73.3% specificity. Conclusions: HMGB1 is as useful as fecal calprotectin in assessing intestinal inflammation in IBD with a significant correlation with disease severity. HMGB1 performs better in UC while fecal calprotectin in CD.

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OC.02.6 IDENTIFICATION OF A CUT-OFF FOR PERSISTENT ANTIINFLIXIMAB ANTIBODIES AS A PREDICTOR OF RESPONSE TO INFLIXIMAB MONOTHERAPY Del Nero L.*2, Bodini G.2, Giannini E.G.2, Savarino V.2, De Maria C.2, Baldissarro I.2, Savarino E.1 Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua,, Padua, Italy, 2 Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy, Genoa, Italy

1

Background and aim: The clinical and predictive role of antiInfliximab antibodies (AIA) presence and concentration are still debated, both in Crohn’s disease (CD) and ulcerative colitis (UC) patients. However, there is increasing evidence of their usefulness in order to improve the management of patients on biological treatment who experience a loss of response (LOR). AIA can be subdivided into 2 types, persistent and transient, on the basis of their occurrence on multiple samples and capability of interfering with infliximab trough levels (TL), and therefore persistent AIA seem to play a major role on treatment outcome. The aim of our retrospective study was to evaluate the clinical relevance of persistent AIA in a single-center cohort of inflammatory bowel disease (IBD) patients. Material and methods: We selected from our cohort of 56 IBD patients treated with IFX mono-therapy who achieved clinical and biochemical remission after induction (IFX schedule: 5 mg/kg at week 0, week 2, and week 6), 18 patients (32.1%) who developed persistent AIA during 48 weeks follow-up. Blood samples were drawn at standardized time points (i.e., baseline, 2 weeks, 6 weeks, and every 8 weeks) before IFX infusion. TL and AIA were measured using an homogenous mobility shift assay (HMSA; Prometheus Lab, San Diego, United States). Clinical disease activity was assessed both at week 14 (i.e. after induction) and week 48 by the HarveyBradshaw Index (HBI, remission defined by HBI<5) in CD patients and by the Mayo score for UC patients (remission defined by Mayo score <2). Also, protein-C reactive and erythrocyte sedimentation rate (ESR) were measured. Results: Eighteen patients (11 CD and 7 UC, 10M/8F, median age 39.5 years, range 18-69) developed persistent AIA at a median of 2 weeks (range 2-22) during 48 weeks follow-up. Among these patients, 12 (66.7%) experienced LOR during the follow-up period. Median AIA were significantly higher in patients who showed LOR as compared to patients who maintained remission (8.29 U/ml, range 0.62-30.52 U/ml, versus 1.41 U/ml, range 0.77-9.94 U/ml; P=0.04). ROC curve identified a persistent AIA cut-off of 3.91 U/mL as the threshold with the highest accuracy for the identification of relapsers (AUROC=0.799, specificity=75.0%, sensitivity=83.3%). Conclusions: The early occurrence of elevated persistent AIA serum concentrations during IFX mono-therapy treatment is associated with high risk of LOR. Furthermore, the use of an AIA concentration cut-off of 3.91 U/mL can be useful to accurately identify patients with LOR, although these results need to be confirmed in larger series.

OC.02.7 ADALIMUMAB TROUGH LEVELS AT WEEK EIGHT AS PREDICTIVE FACTOR OF LONG TERM CLINICAL REMISSION Pellegatta G.*2, Moscatelli A.2, Savarino V.2, Savarino E.1, Bodini G.2, Baldissarro I.2, Giannini E.G.2 Surgery oncology and Gastroenterology, University of Padua, Padua, Italy, 2Internal Medicine, IRCCS San Martino Internal Medicine Department, Genoa, Italy

1

Background and aim: Adalimumab (ADA) has been approved for the treatment of Crohn’s disease refractory to standard medications.