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Abstracts of the 22
nd
National Congress of Digestive Diseases / Digestive and Liver Disease 48S2 (2016) e67–e231
e77
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,
2
Dipartimento di
Radiobiologia e Salute dell’Uomo, ENEA, Roma, Italy,
3
Dipartimento
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.
OC.02.6
IDENTIFICATION OF A CUT-OFF FOR PERSISTENT ANTI-
INFLIXIMAB 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
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
Background and aim:
The clinical and predictive role of anti-
Infliximab 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 Harvey-
Bradshaw 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
1
Surgery oncology and Gastroenterology, University of Padua, Padua,
Italy,
2
Internal Medicine, IRCCS San Martino Internal Medicine
Department, Genoa, Italy
Background and aim:
Adalimumab (ADA) has been approved for
the treatment of Crohn’s disease refractory to standard medications.