Download P406 Predictive factors of refractory to tacrolimus therapy in patients

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61 months. Independent predictors of relapse-free survival
were combined use of IMM during IFX induction [Odds ratio 1.47
(95% CI 1.04 2.08), p = 0.031] and short-term complete clinical
response [3.30 (2.33 4.67), p < 0.001]. IFX dose optimization
was performed in 100 patients (76%) and was successful in
half of them. During a median follow-up of 65 months, 56 of
the 277 patients (20%) needed colectomy (Figure). Independent
predictors of colectomy-free survival were short-term clinical
response [11.23 (5.71 21.74), p < 0.001], a baseline CRP
5 mg/L [2.50 (1.22 5.26), p = 0.012] and a baseline albumin
35 g/L [2.33 (1.12 3.23), p = 0.024]. Nine out of 37 patients
(24%) with IV steroid-refractory UC required colectomy. During
IFX therapy, 99 of 127 patients under CS at baseline (78%) could
definitively stop CS. Furthermore, 17 infectious adverse events
necessitating hospitalization occurred. Throughout followup, 20 patients developed a malignancy and 10 patients
died. Short- and long-term post-operative complications were
observed in 53% and 58%, respectively.
Poster presentations
perianal fistulae, postop. smoking, postop. medications were
noted. Rutgeerts score was used to define postop. endoscopic
recurrence.
Results: The patients’ mean age±SD at their final colonoscopy
was 42.81±11.99 yr, at operation: 36.32±11.23 yr, 45% being
female. The mean follow-up time between resection and the
final colonoscopy was 45 (range, 2 300) months. 13/83 (16%)
patients had their 2nd resection. 45/83 patients (54%) had an
ileocecal resection without any postop. residual disease in the
remnant intestine. 51/83 (61%) patients were in endoscopic
remission whereas 32 (39%) were not. There was no difference
regarding age at disease onset, at operation, at colonoscopy,
and the time from resection to the latest colonoscopy, sex
or disease duration, behavior, location, smoking status, and
family history between patients with and without endoscopic
recurrence. 9/32 (28%) with endoscopic recurrence compared
to 4/51 (8%) without relapse had a history of a 2nd resection
(p = 0.013), disclosing a 3.58 (1.2 10.68) fold risk for relapse.
The presence of any postop. residual disease was another risk
factor [p = 0.015; OR: 1.77 (1.12 2.8)] but the regular use of
azathioprine (AZA), defined as its use at least in 85% of postop.
time period, was found to be a protective factor [p = 0.022;
OR: 1.35 (1.06 1.72)]. In a logistic regression analysis all the
three variables proved to be independent predictors of relapse
(p = 0.013, p = 0.015, p = 0.022 for a history of a 2nd resection,
for the presence of any postop. residual disease, and for the
absence of regular AZA use, respectively).
Conclusions: Having multiple resections for CD was identified
as one of the risk factors for endoscopic recurrence, and the
strict regular use of AZA seemed to add a little positive effect
in preventing endoscopic relapse. The presence of any residual
disease after resection came out as an independent risk factor
for relapse, an issue never mentioned in previous reports.
P406
Predictive factors of refractory to tacrolimus therapy in
patients with active ulcerative colitis
Figure: Colectomy-free survival.
Conclusions: With a median follow-up of 65 months, 20%
of 277 patients treated with IFX for refractory UC needed
colectomy. Short-term clinical response, normal baseline CRP
and normal baseline albumin were independently associated
with colectomy-free survival.
P405
Predictors of endoscopic recurrence in a long term follow
up cohort of Crohn’s disease patients How effective is
azathioprine? A single tertiary referral center experience
Y. Erzin1 *, G. Sisman1 , I. Hatemi1 , B. Baca2 , I. Hamzaoglu3 ,
A. Dirican4 , A.F. Celik1 . 1 Istanbul University Cerrahpasa
Medical Faculty, Gastroenterology, Istanbul, Turkey, 2 Istanbul
University Cerrahpasa Medical Faculty, Surgery, Istanbul,
Turkey, 3 Istanbul Univesrity Cerrahpasa Medical Faculty,
Surgery, Istanbul, Turkey, 4 Istanbul University Istanbul Medical
faculty, Biostatistics, Turkey
Background: Aim was to determine the predictors of
endoscopic recurrence in a cohort of CD patients with prior
intestinal resections.
Methods: CD patients’ charts were reviewed in a retrospective
manner. 104 of 537 (19%) CD patients had a history of prior
intestinal resection. 21/104 (20%) were either lost to follow-up
or had no postoperative (postop.) colonoscopy, so 83 patients
were eligible for the final analysis. Age at disease onset,
at resection, at the last postop. colonoscopy; presence of
family history, sex, disease location, and behavior, presence of
Y. Yokoyama1 *, K. Watanabe2 , N. Hida1 , K. Nogami1 ,
K. Kamikozuru1 , K. Tozawa1 , K. Nagase1 , K. Fukunaga1 ,
T. Matsumoto1 . 1 Hyogo College of Medicine, Department
of Internal Medicine, Division of Lower Gastroenterology,
Nishinomiya, Japan, 2 Graduate School of Medicine, Osaka City
University, Department of Gastroenterology, Osaka, Japan
Background: Although tacrolimus (TA) is recognized as an
effective therapy for induction remission in intractable patients
with ulcerative colitis (UC), there are some refractory cases
in spite of appropriate TA dose adjustment. Therefore, the
evaluation of predictors for refractory including surgery is
important issue for suitable treatment strategy. The aim of the
present study is to investigate the predictors for refractory to
TA therapy in patients with active UC.
Methods: Forty-seven patients who had been treated with TA
for active intractable UC were investigated retrospectively.
Clinical UC activity was assessed with the Lichtiger’s
clinical activity index (CAI) and Mayo score. The refractory
case was defined as underwent surgery or changing to
alternative treatment during TA therapy with high trough level
(10 15 ng/ml, at least 7 days). We compared to evaluate the
predictors between the response group and refractory group
with multivariate analysis for patients’ demographic variables.
Results: The median of age was 35.5 years, duration of
disease was 4.5 years, CAI was 10.3 and Mayo score was 8.0
for enrolled patients. Nine cases (19.1%) were refractory to
TA therapy. Among them, 7 cases underwent surgery and 2
cases were changed to infliximab. The median interval from
the achieving high TA trough level to the evaluation as TArefractory was 18.7 days (7 34days). At baseline, both of CAI
and Mayo score were significantly higher in the refractory group
than the response group (p = 0.016 and p = 0.023, respectively).
Clinical: Therapy and observation
And the dose of prednisolone (PSL) at baseline was also
significantly higher in the refractory group than the response
group (p = 0.005). Multiple logistic regression analysis showed
that high daily PSL dose (p = 0.032, 95% CI 1.014 1.363) at
baseline and high CAI score at 7 days after achieving high trough
level (p = 0.047, 95% CI 1.007 3.065) were significant predictive
factors for the refractory to TA therapy.
Conclusions: Higher activity and higher daily PSL dose at
baseline, poor response at 7 days after achieving high trough
level were predictive factors for refractory to TA therapy. These
refractory patients should be changed to alternative treatment
including surgery without missing the appropriate timing.
P407
Predictive factors for the efficacy of leukocytapheresis
in ulcerative colitis
K. Mitsuyama1 *, K. Nagayama1 , H. Takedatsu1 , T. Kobayashi1 ,
H. Yamasaki1 , K. Kuwaki1 , S. Yoshioka1 , O. Tsuruta1 ,
M. Sata1 . 1 Kurume University School of Medicine, Division of
Gastroenterology, Department of Medicine, Kurume, Japan
Background: Leukocytapheresis (LCAP) has been reported to be
a safe and effective treatment for active ulcerative colitis (UC).
However, the factor predicting the efficacy of LCAP had not
been yet established. The aim of this study was to perform the
univariate analysis of the predictive factor for the efficacy of
LCAP in patients with UC.
Methods: Between October 2001 and March 2011, LCAP therapy
was conducted in Kurume University Hospital for 41 patients
with moderate to severe UC which involves the left-sided
to entire colon. These patients received the LCAP treatment
from total 5 to 10 sessions once weekly. Disease activity was
evaluated clinically by the Lichtiger’s clinical activity index
(CAI) and endoscopically by the Rachmilewitz index. Univariate
analysis in retrospective based on the patient’s case record
was performed to identify the predictive factors which affected
the therapeutic effect [1], the rapid response (responds within
3-sessions of LCAP) [2], and the long term remission [3].
Results: [1] The LCAP treatment showed 75.0% of clinical
remission (Lichtiger’s CAI of 4 or less than) and 11.1% of
clinical response (the reduction of 5 points or half from
baseline). A significant difference (p = 0.0369) was observed
in body mass index with univariate analysis performed
between clinical responders and non-responders. [2] 47.2%
of the LCAP-treated patients had rapid effects (the clinical
remission and response after 3 LCAP sessions). The sex
differed significantly between rapid responders and non-rapid
responders (p = 0.0411). [3] Patients with male (p = 0.0222),
first attack (p = 0.0005), elevated CRP levels (pre-treatment
level, p = 0.0041), high leukocyte counts (post-treatment level,
p = 0.0181), low endoscopic scores (post-treatment level,
p = 0.0282) and low erythrocyte sedimentation rate (posttreatment level, p = 0.0029) achieved a long-term remission.
Conclusions: This study demonstrates the clinical efficacy of
LCAP in active UC patients and also indicates that the induction
of remission by repeated sessions of LCAP therapy is important
to maintain the long-term remission.
P408
Prediction of clinical responders to treatment with
DIMS0150 a Toll-Like Receptor 9 agonist in therapy
refractory ulcerative colitis patients
O. von Stein1 *, E. Musch2 , R. Löfberg3 , N. Kuznetsov1 ,
P. von Stein1 . 1 InDex Pharmaceuticals, Stockholm, Sweden,
2
Marienhospital, Clinic of Colo-Proctology, Bottrop, Germany,
3
IBD unit Sophiahemmet and the Dept of Medicine, Karolinska
Institutet, Stockholm, Sweden
Background: Previous clinical studies suggest that local rectal
administration of the Toll-Like Receptor 9 (TLR9) agonist
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in therapy refractory UC patients induced clinical response
and remission. Clinical improvements were paralleled by a
restoration of steroid sensitivity in vitro as determined by the
use of specific biomarkers. The aim of the presented study was
to determine whether patients mostly likely to benefit from
DIMS0150 treatment could be identified through the use of
these specific biomarkers.
Methods: We investigated, in the context of a randomized,
placebo controlled clinical study, whether screening of a preselection of steroid response genes could identify steroid
refractory UC subjects most likely to respond to DIMS0150
treatment. Expression analysis of 34 steroid response genes
were performed in vitro in peripheral blood mononuclear cells
(PBMCs) derived from in 9 steroid refractory UC patients
and compared to healthy volunteers. Clinical utility of the
biomarkers was subsequently tested in a placebo controlled,
randomized, double blinded study in active therapy resistant
UC patients on concomitant steroid therapies.
Results: We identified two biomarkers CD163 and TSP1 whose
response to steroids was significantly enhanced when DIMS0150
was applied in vitro. Thirty-four subjects were randomized
to receive a single rectal administration of placebo or 30 mg
of DIMS0150. Blood derived PBMCs were obtained prior to
dosing and assayed for evidence of a steroid sensitizing effect
following steroid incubation in the presence of DIMS0150.
Upon study completion and un-blinding, the biomarker assay
correctly predicted a clinical response in over 90% of those
patients positive for both biomarkers. The clinical response
rate in this positively identified group was impressive being
over 80% for active at weeks 1 and 4 with a delta of over 50% to
placebo. By contrast, patients with a negative outcome for the
biomarkers had a response rate no different to placebo being
14% and 27% at weeks 1 and 4 respectively.
Conclusions: Using specific steroid response biomarkers,
therapy refractory UC patients more likely to benefit from
DIMS1050 treatment could be identified and illustrates the
usefulness of a personalized treatment approach.
P409
Physician knowledge of reproductive issues in inflammatory
bowel disease is highly variable
V. Huang1 *, K. Kroeker2 , K. Goodman2 , L. Dieleman2 ,
R. Fedorak2 . 1 University of Alberta, Edmonton, Canada,
2
University of Alberta, Canada
Background: Reproductive care during inflammatory bowel
disease (IBD) can be challenging in its multifactorial nature.
Physicians must consider the impact of IBD and its treatment on
fertility, pregnancy, and neonatal outcome. While women with
inactive IBD have outcomes similar to the general population,
patients with active IBD are faced with decreased fertility and
varied fetal outcomes. There is a higher rate of voluntary
childlessness in women with IBD compared to the general
population, with this decision often being made because
of the IBD diagnosis. Our previous study assessing patient
knowledge of reproductive issues in IBD demonstrated that
patient knowledge regarding reproductive issues in IBD was
poor, despite 50% reported discussing these issues with their
physicians. The aim of this study was to assess, in physicians
treating women with IBD, their IBD-related reproductive
knowledge and their practice in discussing this knowledge with
IBD patients.
Methods: Physicians attending a national IBD conference,
and a provincial gastroenterology for general practitioners
conference both in 2012, were invited to complete a survey
package consisting of: 1) Crohn’s and Colitis Pregnancy
Knowledge (CCPKnow) score and 2) questionnaire regarding
individual practice patterns. The validated CCPKnow score
differentiates between poor (0 7), adequate (8 10), good
(11 13) and very good (14 18) reproductive knowledge.