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Poster presentations
P484
Identification of clinical and genetic predictors of response
to therapy in patients with ulcerative colitis (UC)
P. Ferreira1 *, P. Sousa2 , P. Moura Santos2 , P. Ministro3 , J. de
Deus4 , L. Tavares2 , P. Peixe5 , J. Velosa2 , M. Brito1 , M. Cravo6 .
1
Escola Superior de Tecnologia da Saúde de Lisboa, Lisboa,
Portugal, 2 Hospital Santa Maria, Lisboa, Portugal, 3 Hospital
S. Teotónio, Viseu, Portugal, 4 Hospital Fernando Fonseca,
Lisboa, Portugal, 5 Hospital Egas Moniz, Lisboa, Portugal,
6
Hospital Beatriz Ângelo, Loures, Portugal
5ASA Corticosteroids Azathioprine Biologics
Responders
107
Non-responders 42
49
6
28
19
18
6
Clinical and demographic variables were recorded. A total of ten Single Nucleotide Polymorphisms (SNPs) were
studied: MDR1C3435T and G2677T/A, IL23RG1142A, C2370A,
G43045A and G9T, CASP9C93T, FASG670A, FASLGC844T and
ATG16L1A898G. Genotyping was performed by real time PCR,
with Taqman Probes.
Results: Individuals with the mutant allele for MDR1G2677T/A
were more often diagnosed after 16 yrs (OR6.61 95% CI
(1.18 37.01), p = 0.03) and individuals with the mutant allele
for MDR1C3435T had the disease for less than 5 years
(OR0.34 95% CI (0.15 0.76), p = 0.01). Carriers of the mutant
allele for IL23RG43045A had a significantly higher probability
of developing extra intestinal manifestations (EIM) (OR3.52
95% CI (1.40 8.84), p = 0.01). Regarding response to therapy
we observed that older patients were more prone to respond
to 5ASA (0R6.71 95% CI (1.04 43.21), p = 0.05), while those
with an extensive disease (E2 and E3) were less likely to
respond to 5ASA (OR0.11 95% CI (0.01 0.96), p = 0.05 and
OR0.03 95% CI (0.01 0.27), p = 0.001, respectively). Individuals
with EIM were more often refractory to 5ASA (OR0.20
95% CI (0.08 0.50), p = 0.001), to azathioprine (OR0.20 95% CI
(0.05 0.86), p = 0.03) and corticodependent (OR0.23 95% CI
(0.07 0.79), p = 0.02). In respect to genetic predictors of
response we found that homozygotes AA for IL23RC2370A
were more often corticodependent (OR0.16 95% CI (0.03 0.76),
p = 0.02).
Conclusions: Besides extension of disease, which has been
associated with increased need of IS, the presence of EIM is
a marker of refractoriness to 5ASA and azathioprine as well as
of corticodependency. IL23R SNPs are not only associated with
EIM as well as with corticodependency.
Study supported with grant GEDII 2009 2012.
Background: Iron deficiency anaemia (IDA) is common in
patients with gastrointestinal (GI) disease due to multiple
factors: blood loss, malnutrition, malabsorption and chronic
disease. While oral iron is the preferred first-line treatment
for patients with IDA, many patients cannot take oral iron, do
not tolerate it or do not adequately respond. Oral iron may be
inappropriate or ineffective for some patients, often the case in
patients with inflammatory bowel disease. Ferumoxytol (FER)
is an IV iron approved in the USA, Canada, Switzerland and
the EU for the treatment of IDA in adult patients with chronic
kidney disease with a dosing regimen that permits the delivery
of a full 1 g course of iron in 2 510 mg doses, 3 8 days apart.
Few studies have evaluated IV iron treatment in head-to-head
comparisons. This randomized, controlled trial was designed
to investigate the efficacy and safety of FER compared to iron
sucrose (IS) for the treatment of IDA in patients with a history
of unsatisfactory oral iron therapy or in whom oral iron could
not be used.
Methods: This multicentre open label study was designed to
demonstrate the non-inferiority (NI) of FER to IS. GI patients
(n = 204) with IDA, (haemoglobin 7 10 g/dL and transferrin
saturation <20%) were randomized 2:1 to receive either 2
injections each of 17 ml FER 510 mg (n = 138), 2 to 8 days
apart, or 5 infusions or injections each of IS 200 mg (n = 66)
over 14 days. Efficacy and safety assessments were conducted
weekly from Baseline to Week 5.
Results: FER was shown to be non-inferior (NI) to IS in the
proportion of subjects with a >2 g/dL increase in haemoglobin
(Hgb) at any time from Baseline to Week 5 (FER, 80.4%; IS
80.3%) with the lower bound of the 95% CI ( 11.5%) above the
predefined NI margin ( 15%). FER also achieved NI to IS in the
mean change in Hgb from Baseline to Week 5 with a 2.7 g/dL
increase in Hgb compared to 2.5 g/dL with IS. The incidence
of overall AEs was similar between the two treatment groups:
71 (34.8%) subjects reported Adverse Events (AEs 34% FER, 36%
IS), of which 41 AEs in 22 (10.8%) subjects (8.7% FER, 15.2% IS)
were treatment related. Serious Adverse Events (SAEs) were
reported at comparable frequencies (3.6% FER, 3.0% IS), and
no treatment related SAEs were reported.
Conclusions: In this randomized, controlled trial, the efficacy
and safety of 2 doses of FER were comparable to 5 doses of IS
in treating GI patients with IDA and a history of unsatisfactory
oral iron therapy or in whom oral iron could not be used.
P486
Intravenous corticosteroids in moderate active ulcerative
colitis not responding to oral corticosteroids
J. Llaó1 , J.E. Naves2 *, A. Ruiz-Cerulla3 , L. Marín2 , M. Mañosa4 ,
L. Rodríguez-Alonso3 , E. Cabré4 , E. Garcia-Planella1 ,
J. Guardiola3 , E. Domènech4 . 1 Hospital Santa Creu i
Sant Pau, Gastroenterology, Barcelona, Spain, 2 Hospital
Universitari Germans Trias I Pujol, Dept. of Gastroenterology,
Badalona, Spain, 3 Hospital Universitari Bellvitge-IDIBELL,
Gastroenterology, L’Hospitalet de Llobregat, Spain, 4 Hospital
Universitari Germans Trias I Pujol-CIBEREHD, Dept. of
Gastroenterology, Badalona, Spain
Background: Oral corticosteroids (CS) remain the mainstay
of conventional therapy for moderate flares of ulcerative
colitis (UC). In patients who fail to respond to oral CS, it is
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Background: A third of UC patients are refractory to 5ASA
compounds will need immunossupression (IS) and/or biologics.
We aimed to identify clinical and genetic predictors of response
to therapy in patients with UC.
Methods: We included 159 UC patients, 90 female and 69
males, with a mean age of 47±16.2 yrs and a disease duration of
11±9.4 yrs. Patients were classified as responders based on long
term sustained remission lasting at least one year, not needing
steroids, surgery or escalation of therapy. Patients’ response to
therapies is shown in the table.
P485
IV iron treatment of iron deficiency anaemia with
Ferumoxytol in patients with gastrointestinal disorders
unable to take oral iron: a randomized controlled trial
versus iron sucrose
D. Hetzel1 *, W. Strauss2 , K. Bernard3 , J. Li3 , L. Allen3 . 1 Royal
Adelaide Hospital, Gastroenterology & Hepatology, Adelaide,
Australia, 2 AMAG pharmaceuticals Inc, Medical Director,
Lexington MA, United States, 3 AMAG pharmaceuticals Inc,
Lexington MA, United States
Clinical: Therapy and observation
P487
Infliximab in moderate-to-severe ulcerative colitis: efficacy
and safety in a “real life” retrospective multicenter study
from southern Italy
M. Cappello1 *, M. Mazza1 , G. Costantino2 , W. Fries2 ,
A.C. Privitera3 , M. Mastronardi4 , F. Bossa5 , F. Castiglione6 ,
A. Rispo6 , A. Lauria7 , N. Buccianti8 , R. Marasco9 , P.L. Almasio1 .
1
Gastroenterology Section, Di.Bi.Mis, Palermo, Italy,
2
Messina, Medicina Interna, Messina, Italy, 3 Azienda
Ospedaliera per l’Emergenza, Ospedale Cannizzaro, Catania,
Italy, 4 IRCSS Castella Grotte (BA), UOC Gastroenterologia
ed Endoscopia Digestiva, Castellana Grotte (BA), Italy,
5
Casa Sollievo della Sofferenza, Gastroenterologia, San
Giovanni Rotondo (FG), Italy, 6 Università Federico II,
Gastroenterologia, Napoli, Italy, 7 A. O. Bianchi-MelacrinoMorelli, Reggio Calabria, Gastroenterologia, Reggio Calabria,
Italy, 8 A. O. S. Carlo, Potenza, U.O.C. di Medicina Interna,
Potenza, Italy, 9 Policlinico Catanzaro, UOC Gastroenterologia,
Catanzaro, Italy
Background: Infliximab (IFX) has been shown effective both
for induction and maintenance of remission in moderate-tosevere ulcerative colitis (UC). The aim of this retrospective
multicenter study is to provide data on short and long-term
efficacy and safety of IFX in UC in “daily clinical practice”
patients.
Methods: All consecutive patients with UC who received at
least one infusion of IFX from January 2008 to June 2012
in nine centers from Southern Italy were evaluated. Clinical
and demographic characteristics, IFX indications, concomitant
medications, disease activity (Mayo score), date of colectomy,
and adverse events were registered. Outcomes of efficacy were
clinical and endoscopic responses at week 14 and 52, steroidfree remission and colectomy rate.
Results: The study included 257 adult patients with UC (58.4%
males, mean age 35.7, range 10 78) treated with scheduled
IFX 5 mg/kg. Median duration of UC diagnosis was 50 months
(IQR 18 115), and the extension of disease was pancolitis
in 185 (72.0%) subjects, left-sided colitis in 57 (22.2%), and
proctosigmoiditis in 15 (5.8%). Indications to IFX were steroid
dependence in 74.7% of patients, steroid-resistance in 23.0%,
extra-intestinal complications in 2.3%. Thiopurine failure was
reported in 40.5% of subjects. IFX was used as rescue therapy
in 5.8% of patients with severe refractory UC. Patients received
a median of 9 infusions (range 1 40) and median follow-up
was 26 months. IFX optimization was necessary in 39 (15.2%).
Overall median Mayo score was 9 (IQR 7 10) at enrolment, 5
(IQR 2 6) at 14 weeks and 3 (IQR 1 5) at 52 weeks (p < 0.001 by
Anova). Remission rates were 32% at week 14, 39.4% at week 52.
The rate of patients able to stop steroids was 42.0% at 14 weeks
and 40.5% at 52 weeks. Mucosal healing was obtained in 56.7%.
Colectomy was performed in 22 patients (8.6%). Median time
to colectomy was 7.1 months. Adverse events were observed in
51 (19.8%) of patients: 20 infusion reactions, 22 opportunistic
infections (7 patients with shingles). Four subjects developed
“de novo” neoplasia (2 colo-rectal carcinoma).
Conclusions: This is the first report of a large open-label
multicenter Italian series in a “real life” setting. Infliximab
is a safe and effective treatment in avoiding colectomy
and inducing both short and long-term clinical response and
mucosal healing in moderate-to-severe UC.
P488
Impact of complementary and alternative medicine on
quality of life in IBD patients
S. Nahon1 *, P. Lahmek2 , A. Buisson3 , A. Olympie4 ,
C. Poupardin5 , S. Chaussade6 , B. Lesgourgues5 , V. Abitbol6 .
1
Groupe Hospitalier Le Raincy-Montfermeil, Gastroenterology,
Montfermeil, France, 2 Hôpital Emile Roux, France,
3
Association François Aupetit, Paris, France, 4 Association
François Aupetit, France, 5 GHI Montfermeil, France, 6 Hôpital
Cochin, Gastroenterology, France
Background: Complementary and alternative medicine (CAM)
are widely used by IBD patients. However, only few data have
been published concerning the impact of CAM on quality of life
(QOL).
Methods: From December 2011 to March 2012, we have
conducted an Internet survey of CAM through the website of
the French association of IBD patients (AFA). Patients belonging
or not to the association were invited to answer a questionnaire
using the LimeSurvey application. The questionnaire contained
four parts: 1) socio-demographics of IBD, 2) IBD treatment,
3) CAM type [a) naturopathy, b) manipulative and body-based
practices, c) traditional medicine and homeopathy, d) herbal
products or dietary supplements and e) meditation and spiritual
approach], 4) socioeconomics data and small IBDQ (SIBDQ).
Moreover, the patient had to note the impact of CAM on his
disease’s symptoms and on his quality of life on a scale from 0
to 100.
Results: 767 (82.3%) patients completed the whole questionnaire. 503 (65.6%) reported using CAM, 172 (22.4%) had never
used them and 92 (12%) had used CAM. CAM were based
on naturopathy in 15.2% of the cases, on manipulative and
body-based practices in 25.1% of the cases, on homeopathic
or traditional medicine in 19.6% of the cases, on dietary
supplements in 30.7% of the cases and on meditation in 9.1%
of the cases. CAM users (compared with non users) were more
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recommended to attempt the intravenous (i.v.) route before
starting rescue therapies, although no evidence supports this
strategy.
Aims: To evaluate the efficacy of i.v. CS in moderate attacks
of UC according to previous failure to oral CS or not, and to
identify differences in long-term outcomes.
Methods: UC patients admitted to 3 University hospitals
between January 2005 and December 2011 were identified from
electronic databases. Disease severity was defined according
to the Montreal classification, and only patients with moderate
active UC treated with i.v. CS were included. Patients were
grouped depending on previous treatment with oral CS for the
index flare. Main end-points were: initial efficacy (defined as
mild or inactive disease according to Montreal classification at
day 7 after starting i.v. CS without rescue therapy) and the
long-term clinical outcome (steroid dependency, colectomy).
Results: 110 attacks were included (89 patients), with a median
time from UC diagnosis of 28 months (IQR, 3 108). 45% of them
were initially treated with oral CS without response, with a
median dose of 60 mg/d (IQR, 50 60) and during a median time
of 10 days (IQR, 7 17). No differences in clinical features and
biological parameters between both groups, except for younger
age and lower C-reactive protein levels at the beginning of
i.v. CS in the group of patients initially treated with oral CS.
The i.v. CS dose was 60 mg/d (IQR, 50 60) and the median
concentration of C-reactive protein at the beginning of i.v.
treatment was 44 mg/L (IQR, 16 88). Initial response was
achieved in 75%, without differences between the both study
groups (78% vs. 75%). Rescue therapy during the admission was
required in 26% of cases, with a colectomy rate of 3%. No
predictive factors to initial response to i.v. CS were found.
After a median follow-up of 12 months (IQR, 4 24), 35% of
initial responders developed steroid-dependency and up to 13%
required colectomy. The unsuccessful response to oral CS was
the only factor associated to steroid-dependence in the longterm (54% vs. 18%, P = 0.001).
Conclusions: Intravenous CS are efficient for inducing remission
in moderately active UC not responding to oral CS, but almost
half of the patients develop steroid-dependency later on.
Alternative therapeutic strategies should be assessed in this
clinical setting.
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