British Society of Gastroenterology Annual General Meeting 20–23 June 2016 Abstracts

314 Pages·2016·3.51 MB·English

June 2016 Volume 7 Supplement 1
7
S1
V
o
lu
m
e
7

S
u
p
p
le
m
e
n
t
1

P
a
g
e
s
A
1
–
A
3
1
0
G
U
T
British Society of Gastroenterology
Annual General Meeting
20–23 June 2016
Abstracts
Ju
n
e
2
0
1
6
Aims and Scope: Gut is a leading international journal in gastroenterology and
hepatology with an established reputation for publishing fi rst class clinical research
of the alimentary tract, the liver, biliary tree and pancreas likely to impact on clinical
practice within the foreseeable future. Gut delivers up-to-date, authoritative, clinically
Journal of the British Society of Gastroenterology, oriented coverage of all areas in gastroenterology. Regular features include articles
a registered charity
by leading authorities, commentaries on published papers, recent advances in basic
Editor
Emad El-Omar (Australia) science and clinical practice, images illustrating important clinical messages
Deputy Editor (Hepatology) (GI snapshots) and letters. The Journal has an authoritative global Editorial Board and
Alexander Gerbes (Germany)
a growing international readership.
Deputy Editor
(Luminal Gastroenterology)
William Grady (USA) Editorial Board
Deputy Editor (Endoscopy) Contact Details
Thomas Rösch (Germany) A Adolph (Austria) K E L McColl (UK)
A Aghemo (Italy) P Michl (Germany)
Associate Editors R Bataller (Spain) S Moller (Denmark) Editorial Offi ce
Matias Avila (Spain) D C Baumgart (Germany) D J Mutimer (UK) Gut, BMJ Journals
Martin Blaser (USA) A Benesic (Germany) F Negro (Switzerland) BMA House, Tavistock Square
Guy Boeckxstaens (Belgium) C Berasain (Germany) J M Neuberger (UK) London, WC1H 9JR, UK
Patrice Cani (Belgium) MA BBeerrtnoalertdtii ((IStainlyg)apore) SJ POagnineos ((USSpaAi)n) T: [phone]
Silvio Danese (Italy) U Beuers (The Netherlands) L Peyrin-Biroulet (France) E: [email protected]
Thomas Gress (Germany) A Blackshaw (UK)
M Pinzani (UK)
Arthur Kaser (UK) J Bosch (Spain) H Pohl (Italy) Production Editor
J Brahm (Chile)
Ernst Kuipers (The Netherlands) Z-H Ran (China) Teresa Jobson
A J Bredenoord (The Netherlands)
Jake Liang (USA) J Bruix (Spain) F X Real (Spain) E: [email protected]
Herbert Tilg (Austria) M Buchholz (Germany) N Reddy (India)
Fabien Zoulim (France) M Camilleri (USA) A Salas (Spain) Permissions
L Castera (France) A Sanyal (USA) http://journals.bmj.com/misc/permissions.dtl
Statistics Editor H L Y Chan (Hong Kong) J Schoelmerich (Germany)
Mariana Lazo (USA) K Chayama (Japan) R Schwabe (USA) Supplement Enquiries
Ruben Hernaez (USA) T Chiba (Japan) T Seufferlein (Germany)
T: [phone]
E N De Toni (Germany) F Shanahan (Ireland)
Specialist Editors P Desreumaux (France) M Simren (Sweden) E: [email protected]
Willem de Vos (The Netherlands) H Diepolder (Germany) J D Sodderholm (Sweden)
Catherine Postic (France) L Egan (Ireland) S Sookoian (Argentina) Subscriptions
Kentaro Sugano (Japan) D M Fan (China) C Steib (Germany) For all subscription enquiries and orders
Joseph Sung (Hong Kong) P Ferenci (Austria) J J Y Sung (Hong Kong) T: [phone]
R Fitzgerald (UK) T Tham (UK)
Education Editor C E Forsmark (USA) R Thimme (Germany) http://support.bmj.com
Mairi McLean (UK) S Fukudo (Japan) S P L Travis (UK)
Guidelines Editor PM G Gibosgognin (sA (uUsStrAal)ia) DG vTuavne Assosnc (hUeS (AT)he Netherlands) DSoispphliea yF iAtzdsivmemrtoisnisng Sales
Tony Tham (UK) S Harrison (USA)
G R van der Brink (The Netherlands) T: [phone]
C Hellerbrand (Germany)
JournalScan Editor G Hold (UK) C J van der Woude (The Netherlands) E: sfi [email protected]
Mairi McLean (UK) J-D Jia (China) S Vermeire (Belgium) http://group.bmj.com/group/advertising
Book Review Editor P Lampertico (Italy) A J M Watson (UK)
Mark Pritchard (UK) SMY M Le Lee (rScohu (tGh eKromreaan)y) RF WWoiensgt ((CSawniatzdear)land) Online Advertising Sales
Social Media Editor L J Li (China) C-Y Wu (Taiwan) Marc Clifford
Philip Smith (UK) J-T Lin (Taiwan) M-S Wu (Taiwan) T: [phone]
J Liu (China) H Yamamoto (Japan) E: [email protected]
Guidelines for Authors and P Lochhead (UK) YS Yang (China) http://group.bmj.com/group/advertising
Reviewers R Loomba (USA) K G Yeoh (Singapore)
Full instructions are available online at J V Mayerle (Germany) S Zeissig (Germany) Display & Online Advertising Sales (USA)
http://gut.bmj.com/ifora. Articles
Jim Cunningham
must be submitted electronically soundcloud.com/bmjpodcasts/ T: [phone]
http://mc.manuscriptcentral.com/gut. facebook.com/Gut.BMJ sets/gut-podcast E: [email protected]
Authors retain copyright but are required
to grant Gut an exclusive licence to @Gut_BMJ Author Reprints
publish http://gut.bmj.com/ifora/licence.dtl Reprints Administrator
E: [email protected]
Subscription Information
Commercial Reprints (except USA & Canada)
Nadia Gurney-Randall
Gut is published monthly; subscribers receive all supplements T: [phone]
M: [phone]
Institutional Rates 2016 Personal Rates 2016 E: [email protected]
Print Print (includes online access at no additional cost) Commercial Reprints (USA & Canada)
£816; US$1592; €1102 £325; US$634; €439 Ray Thibodeau
T: [phone]
Online Online only M: [phone]
Site licences are priced on FTE basis and allow £174; US$340; €235 E: [email protected]
access by the whole institution. Details available
ISSN 0017-5749 (print); 1468-3288 (online) British Society of Gastroenterology
online at http://group.bmj.com/group/subs-sales/
subscriptions or contact the Subscription Manager 3 St Andrew’s Place, Regents Park,
in the UK (see above right). London NW1 4LB, UK
T: [phone]
Personal print or online only and institutional print subscriptions may be purchased online at E: [email protected]
http://group.bmj.com/group/subs-sales/subscriptions (payment by Visa/Mastercard only). www.bsg.org.uk
Residents of some EC countries must pay VAT; for details, call us or visit www.bmj.com/subscriptions/
For all other Gut journal contacts
vatandpaymentinfo.dtl
http://gut.bmj.com/site/help/index.xhtml
gutjnl_65_7_EB.indd 1 27/05/16 8:18 AM
S71 June 2016 Volume 7 Supplement 1 Contents Volume 7 Supplement 1 | GUT June 2016
Volume 7 Supplement 1 Pages A1–A310
A1 BSG 2016
GUT
British Society of Gastroenterology A300 Author Index
Annual General Meeting
20–23 June 2016
Abstracts
June 2016
An international journal of
gastroenterology and hepatology
Editor
Emad El-Omar (UK)
Deputy Editor (Hepatology)
Alexander Gerbes (Germany)
Deputy Editor (Luminal
Gastroenterology)
William Grady (USA)
Associate Editors
Matias Avila (Spain)
Guy Boeckxstaens (Belguim)
Laurence Egan (Ireland)
Thomas Gress (Germany)
Ernst Kuipers (The Netherlands)
Julian Panes (Spain)
Herbert Tilg (Austria)
Fabien Zoulim (France)
Editorial Office
Gut
BMJ Journals
BMA House, Tavistock Square
London, WC1H 9JR, UK
T: [phone]
F: [phone]
E: [email protected]
ISSN: 0017-5749 (print)
ISSN: 1468-3288 (online)
Disclaimer: Gut is owned and published by BMJ
Publishing Group Ltd, a wholly owned subsidiary
of the British Medical Association and the British
Society of Gastroenterology. The owners grant
editorial freedom to the Editor of Gut. Gut follows
guidelines on editorial independence produced
by the World Association of Medical Editors and
the code on good publication practice of the
Committee on Publication Ethics.
Gut is intended for medical professionals and is
provided without warranty, express or implied.
Statements in the Journal are the responsibility
of their authors and advertisers and not authors’
institutions, the BMJ Publishing Group, the
British Society of Gastroenterology or the BMA
unless otherwise specifi ed or determined by
law. Acceptance of advertising does not imply
endorsement.
To the fullest extent permitted by law, the BMJ
Publishing Group shall not be liable for any loss,
injury or damage resulting from the use of Gut or
any information in it whether based on contract,
tort or otherwise. Readers are advised to verify any
information they choose to rely on.
Copyright © 2015 BMJ Publishing Group Ltd
and British Society of Gastroenterology. All
rights reserved; no part of this publication may
be reproduced, stored in a retrieval system
or transmitted in any form or by any means,
electronic, mechanical, photocopying, recording or
otherwise without prior permission
Gut is published by BMJ Publishing Group Ltd,
typeset by Exeter Premedia Services Private Ltd.
Gut (ISSN: 0017-5749) is published monthly by
BMJ Publishing Group and is distributed in the USA
by Air Business Ltd. Periodicals postage paid at
Jamaica NY 11431 POSTMASTER: send address
changes to Gut, Air Business Ltd, c/o Worldnet
Shipping Inc., 156-15, 146th Avenue, 2nd Floor,
Jamaica, NY 11434, USA.
Abstracts
BSG 2016 Disclosure of Interest G. Heap Conflict with: Abbvie, T.
Ahmad Grant/research support from: Abbvie, MSD, Hospira,
Inflectra, Conflict with: Abbvie, MSD
OC-001 CLINICALFACTORSTHATDETERMINEPRIMARYNON-
RESPONSE(PNR)TOANTI-TNFDRUGSINPATIENTS
WITHACTIVELUMINALCROHN’SDISEASE(CD)
1,2GA Heap*, 1,2T Ahmad, on behalf of Pants Consortium. 1Department of OC-002 CIRCULATINGDENDRITICCELLSUBSETSINCROHN’S
Gastroenterology,RoyalDevon&ExeterHospital;2PrecisionMedicineExeter,Universityof DISEASESHOWALTERATIONSINTISSUEHOMING
Exeter,Exeter,UK
ANDCYTOKINEPRODUCTION
10.1136/gutjnl-2016-312388.1 1,2PAHendy*,1DReddi,3DBarnardo,1LDurant,1ANoble,1PBhat,1NEnglish,1SCKnight,
1,2ALHart.1APRG,ImperialCollege;2Gastroenterology,StMark’sHospital,London,UK;
Introduction 10–40% of patients with CD fail to respond to 3ResearchUnit(7thfloor),HospitalUniversitariodelaPrincesa,Madrid,Spain
anti-TNF induction therapy at 10–14 weeks. The mechanisms
underlying PNR are uncertain but a better understanding of 10.1136/gutjnl-2016-312388.2
these factors might allow more cost-effective, individualised
Introduction Crohn’s disease (CD) is characterised by an exag-
anti-TNF treatment. We present an interim analysis of PNR in
gerated immune response to mucosal antigen. Dendritic cells
the PANTS cohort.
(DC) are the primary antigen presenting cells and may pro-
Methods The PANTS study is a UK wide, multi-centre 3 year
mote either tolerogenic or inflammatory T cell responses to
prospective, observational cohort study investigating PNR to
mucosal antigens. We characterised homing marker profile and
Infliximab (IFX) and Adalimumab (ADA). Serial collection of
ongoing cytokine production of circulating DC subsets from
clinical data and sampling of DNA, RNA, serum and stool
patients with Crohn’s disease.
will allow down-stream multi-omic studies. Inclusion criteria
include active luminal Crohn’s disease supported by raised Methods DC within peripheral blood mononuclear cells from
adults with active luminal Crohn’s or from healthy controls
CRP or Calprotectin and no prior exposure to anti-TNF ther-
apy. PNR was defined as failure of HBI to fall by (cid:1)3 points (HC) were characterised using flow cytometry. DC were iden-
or to £4 AND failure of CRP to fall by (cid:1)50% or to £3 mg/ tified as HLA-DR+ and negative for markers of other cell lin-
eages (CD3, CD14, CD16, CD19, CD34). Myeloid DC
dL OR failed steroid withdrawal. Drug and anti-drug antibody
(mDC, CD11c+CD123(cid:3)) and plasmacytoid DC (pDC,
levels were measured using Immunodiagnostic drug tolerant
CD11c(cid:3)CD123+) were assessed for phenotype (maturation sta-
assays.
Results 1176 (568 male) patients aged 4.0–77.2 years have tus, homing markers and pattern recognition receptors) and
on-going cytokine production by surface and intracellular
been recruited from 106 sites and reached 14 weeks after
staining, respectively.
quality control. Patients were treated with IFX (695, 59.1%)
Results In patients with Crohn’s (n = 16), a greater propor-
or ADA (481, 40.9%). At entry 39.7% of patients had an
HBI of £4, 32.14% (cid:1) 8, and 29.4% of patients had a tion of myeloid DC expressed a gut-homing profile
CRP £ 3, 42.4% had a CRP (cid:1) 10. Concomitant drugs at (CLA(cid:3)b7+, p = 0.0022) compared to controls (n = 10)
where most myeloid DC were not tissue-specific (CLA+b7+,
entry included steroids 18.5%, azathioprine 39.2%, mercapto-
p = 0.0014, Fig C). In Crohn’s and controls, myeloid DC
purine 7.40%, methotrexate 5.4%. PNR could be assessed at
were largely gut-homing (CLA(cid:3)b7+, p = 0.003) whilst plas-
week 14 for 1090 (92.7%) patients. PNR was observed in
macytoid DC were strongly skin (CLA+b7(cid:3)) and lymph node
16.9% and 23.7% of the IFX and ADA treated patients
(CCR7+) homing (p < 0.0001 e.g. Fig D). Production of pro-
respectively. This difference was not significant once adjusted
inflammatory cytokines was up-regulated in Crohn’s, with
for baseline disease activity (P = 0.2). To date only 2 patients
myeloid DC producing higher levels of TNFa (p = 0.0042,
who met the week 14 PNR criteria achieved remission on
Fig A) and plasmacytoid DC producing higher levels of IL-6
anti-TNF at 1 year (sensitivity 0.99, specificity 0.4). A multi-
(p = 0.013, Fig B). Expression of maturation marker CD86
variate regression identified albumin (P = 0.0036) as associ-
was increased on myeloid DC in Crohn’s but not on plasma-
ated with PNR at Week 14 in the IFX group and drug level
cytoid DC (p = 0.027 and p = 0.13 respectively). Expression
(P = 0.00035), calprotectin (P = 0.033), albumin
of IFN-a, Il-1b, Il-12, CD40, CD80, TLR2 and TLR4 on DC
(P = 0.037) and anti-drug antibody level (P = 0.024) in the
were not different between Crohn’s and controls for either
ADA group. In combined analysis BMI (P = 0.017) and drug
DC subset.
level (P = 0.024) were associated with PNR. 75 IFX and 36
Conclusion The increased myeloid DC expression of gut hom-
ADA patients had anti-drug antibodies at week 14, of which
ing phenotype markers and production of TNFa in Crohn’s
33 and 6 patients had no detectable drug. Development of
compared with controls highlights the central role that DC
anti-drug antibodies in the first 14 weeks was associated with
play in the pathogenesis of Crohn’s disease.
monotherapy (P = 0.00021) and was seen more commonly in
patients with early infusion reactions (P = 2x10(cid:3)16). Differences between homing markers on myeloid DC (gut
homing) and plasmacytoid DC (skin homing) suggest that they
Conclusion The PANTS study has provided a real world esti-
may have different roles in different manifestations of
mate of PNR and associated risk factors in a large prospective
Crohn’s, with myeloid DC being central to gut inflammation
cohort using a simple clinical and biochemical definition at
whilst plasmacytoid DC might be involved in cutaneous
week 14 that predicts non-remission at week 54. Low drug
Crohn’s disease and the skin sequelae of anti-TNFa therapy.
level and immunogenicity are associated with PNR, infusion
DisclosureofInterestNone Declared
reactions and monotherapy suggesting early measurement
might help prevent and manage PNR.
Gut2016;7(1):A1–A310 A1
Abstracts
AbstractOC-002Figure1 A–D:DCproductionofTNFa(A)IL-6(B)&frequencyofCLA+/b7+mDC(C)inHCandCDandofb7+mDCandpDC
inCrohn’s(D)(shown as%DCexpression)
OC-003 EFFICACYANDSAFETYOFGOLIMUMABINDUCTION (cid:1)1 point or an absolute rectal bleeding score £1. Patients
FORMODERATETOSEVEREULCERATIVECOLITISIN without scores were considered nonresponders. Clinical remis-
THEUNITEDKINGDOM:RESULTSFROMTHEGO- sion was defined as partial Mayo score £2 and no individual
COLITISSTUDY Mayo subscore >1.
Results 205 patients were enrolled (mean [range] age, 39.3
1CProbert*,2DGaya,3PJHamlin,4PIrving,5SSebastian,6GGillespie,6HTate,6CWheeler.
1University of Liverpool, Liverpool; 2Glasgow Royal Infirmary, Glasgow; 3Leeds Teaching [18–79] years; male, n = 123 [60%]). The mean baseline
HospitalTrust,Leeds;4Guy’sandSt.Thomas’Hospitals,London;5Hull&EastYorkshireNHS (SD) partial Mayo score was 6.4 (1.4). All patients received
Trust,Hull;6MSDUK,Hoddesdon,UK one or two doses of induction GLM. Clinical responses
occurred in 141/205 patients (response rate, 68.8%; 95% CI,
10.1136/gutjnl-2016-312388.3 62.0%–75.1%). Clinical remission occurred in 79/205 patients
(remission rate, 38.5%; 95% CI, 31.8%–45.6%). The mean
Introduction Induction and maintenance of clinical response is
(SD) change from baseline in partial Mayo score (n = 198)
a treatment goal for ulcerative colitis (UC). GO-COLITIS was –3.2 (2.4). AEs (any cause) occurred in 37 (18%)
(NCT02092285; 2013–004583-56) is a UK phase 4, multi-
patients. Serious AEs occurred in 17 (8%) patients: UC flare/
centre, open-label, single-arm trial evaluating the efficacy of
worsening (n = 11), accidental overdose (n = 2), anaphylaxis
golimumab (GLM) in induction and maintenance of clinical
(n = 1), constipation (n = 1), rectal fissure (n = 1), and res-
response in patients with moderate to severe UC. We report
piratory tract infection (n = 1). Eight patients (4%) discontin-
the results of an interim analysis of clinical response at the
ued due to serious AEs. There were no fatal AEs.
end of the GLM induction phase.
Conclusion During the GLM induction phase of GO-COLITIS,
Methods Anti-TNF naive patients ((cid:1)18 y) with UC (cid:1) 3
68.8% of patients had a partial Mayo response and were eli-
months and with moderate to severe disease (partial Mayo
gible to continue to the 48 week maintenance phase. AEs
score 4–9 or Mayo score 6–12) at baseline, Mayo rectal
were consistent with previous observations; no new safety sig-
bleeding subscore (cid:1)1, and Mayo endoscopy subscore (cid:1)2 (if
nals were identified.
full Mayo was used) were included. Patients received SC
Disclosure of Interest C. Probert Consultant for: Abbvie, MSD,
GLM on day 0 (200mg) and day 14 (100mg) during the 6
Napp, Takeda, Speaker bureau with: Abbvie, Falk, Ferring,
week induction phase, followed by GLM 50 or 100mg every
MSD, Shire, Takeda, Conflict with: Abbvie, Falk, MSD, Shire,
4 weeks during the 48 week maintenance phase with 12 week
Takeda, D. Gaya Speaker bureau with: Abbvie, Falk, Ferring,
follow-up, in line with the Summary of Product Characteris-
MSD, Shire, Takeda, Vifor, Conflict with: Abbvie, Falk, Fer-
tics. Clinical response and remission were summarised descrip-
ring, MSD, Shire, Takeda, Vifor, P. Hamlin Speaker bureau
tively at the end of week 6. Clinical response was defined as
with: Abbvie, Ferring, MSD, Takeda, Tillotts, Warner Chilcott,
decrease in partial Mayo score of (cid:1)2 points and (cid:1)30% from
Conflict with: Abbvie, Falk, MSD, Tillotts, P. Irving Grant/
baseline, plus either a decrease in rectal bleeding subscore of
research support from: MSD, Takeda, Consultant for: Abbvie,
A2 Gut2016;7(1):A1–A310
Abstracts
MSD, Takeda, Warner Chilcott, Vifor Pharma. Pharmacosmos, Baseline Oneyear pvalue
Topivert, Genentech, Hospira, Speaker bureau with: Abbvie, N Mean(IQR) N Mean(IQR) PairedTtest
Falk Pharma, Ferring, MSD, Takeda, Warner Chilcott, Johnson
CDAI 40 332(246–418) 37 193(79–295) <10(cid:3)5
and Johnson, Shire, S. Sebastian Grant/research support from:
PRO2 40 24(16–31) 37 12(4–21) <10(cid:3)5
Abbvie, Ferring, Warner Chilcott, Consultant for: Falk Pharma,
EQ5D 34 0.7(0.7–0.8) 31 0.8(0.7–1) 0.033
Ferring, MSD, Takeda, Warner Chilcott, Vifor Pharma,
IBDQ 37 120(102–141) 31 154(120–201) 0.0007
Speaker bureau with: Abbvie, Takeda, Warner Chilcott, G. Gil-
SESCD 36 14(7–22) 36 5.4(0.3–7) <10(cid:3)5
lespie Shareholder of: MSD UK, Conflict with: Employment
MSD UK, H. Tate Consultant for: MSD UK, C. Wheeler
Shareholder of: MSD UK, Conflict with: Employment MSD
Conclusion One year outcome in the largest reported cohort
UK
of patients undergoing HSCT for refractory Crohn’s disease
shows a significant reduction in both clinical and endoscopic
disease activity with an improvement in quality of life. Endo-
OC-004 PREDICTIONOFCLINICALANDENDOSCOPIC scopic severity at baseline predict outcome.
REMISSIONAFTERAUTOLOGOUSSTEMCELL DisclosureofInterestNone Declared
TRANSPLANTATIONINTREATMENTREFRACTORY
CROHN’SDISEASE:POOLEDRESULTSFROMTHEASTIC
TRIAL
OC-005 AMULTICENTER,DOUBLE-BLIND,PLACEBO(PBO)-
1JOLindsay*,2MAllez,3MClark,4MLabopin,5ERicart,6JSatsangi,7GRogler,5MRovira, CONTROLLEDPH3STUDYOFUSTEKINUMAB(UST),A
2DFarge,3CHawkey,onbehalfofAsticTrialGroup.1Bart’sHealthNHSTrust,London,UK; HUMANIL-12/23P40MAB,INMODERATE-SEVERE
2Hospital St Louis, Paris, France; 3Queens Medical Centre, Nottingham, UK; 4European CROHN’SDISEASE(CD)REFRACTORYTOANTI-TNFA:
GroupforBlood&MarrowTransplantation,Paris,France;5HospitalClinic,Barcelona,Spain;
UNITI-1
6WesternGeneralHospital,Edinburgh,UK;7UniversityHospital,Zurich,Switzerland
1PRutgeerts,2CGasink*,3MBlank,2YLang,2JJohanns,2L-LGao,4BSands,5SHanauer,
10.1136/gutjnl-2016-312388.4 6BFeagan,7STargan,8SGhosh,9WdeVilliers,4J-FColombel,10SDLee,11PDesreumaux,
12EV Loftus, 13S Vermeire, 14WJ Sandborn. 1U Hosp Gasthuisberg, Leuven, Belgium;
Introduction The randomised controlled ASTIC trial compared 2JanssenR&D,Spring House;3JanssenPharmaLLC, Horsham; 4Mt Sinai MedCtr,New
autologous stem cell transplantation (HSCT) with conventional York; 5Northwestern U, Chicago, United States; 6Robarts Res Inst, London, Canada;
care in treatment refractory Crohn’s disease (CD). Although 7Cedars-SinaiMedCtr,LosAngeles,UnitedStates;8UCalgary,Calgary,Canada;9UCape
the trial failed its ambitious primary endpoint (clinical remis- Town,CapeTown,SouthAfrica;10UWashington,Seattle,UnitedStates;11CHRUdeLille,
Hopital Claude Huriez, Lille, France; 12Mayo Clinic, Rochester, United States; 13U Hosp,
sion for >3 months off all CD medication with no ulceration
Leuven,Belgium;14UCSD,LaJolla,UnitedStates
on imaging / endoscopy at 1 year) significant benefit was seen
in individual components. Patients randomised to conventional
10.1136/gutjnl-2016-312388.5
care subsequently underwent HSCT. We report outcome for
all patients 1 year after HSCTand identify factors that predict Introduction In a Ph2b study(CERTIFI),1 UST intravenous(IV)
remission. induction followed by subcutaneous(SC) maintenance was
Methods Patients with active CD who were refrctory biologics effective in moderate-severe CD refractory to anti-TNF ther-
underwent cyclophosphamide mobilisation and were rando- apy. This Ph3 study examined efficacy&safety of IV UST
mised to immediate (4 weeks) or delayed (52 weeks) HSCT. induction in these pts.
Clinical (CDAI), endoscopic (SES-CD), and quality of life Methods Pts with moderate-severe CD(CDAI 220–450) who
scores were compared immediately prior to (baseline) and one previously failed/were intolerant to (cid:1)1 TNF-antagonist were
year after HSCT. An adjudication panel blinded to allocation randomised 1:1:1 at Wk0 to a single dose of IV PBO, UST
and visit reviewed radiology and endoscopy. 130 mg, or weight-based tiered UST dosing ~6mg/kg. Pri-
Results 45 patients with successful mobilisation were rando- mary endpoint was clinical response at Wk6(baseline [BL]
mised to early (n = 23) or delayed (n = 22) HSCT. Data CDAI score reduced by (cid:1)100); pts with BL CDAI (cid:1)220 to
from baseline and 1 year after HSCT were available for 40 £248 were considered in clinical response if CDAI score of
patients. Compared to baseline, there were significant <150 was present. At Wk8, pts transitioned to the IM-UNITI
improvements at 1 year for CDAI, PRO2, quality of life maintenance study or were followed to Wk20.
(IBDQ, and EQ5D) and SES CD (see Table). Complete endo- Results The 741 randomised pts had history of TNF-antago-
scopic regression (SES-CD score of 0 in all segments exam- nist failure, with BL median CDAI = 317, CRP = 9.9mg/L,
ined) occurred in 26%, with complete ulcer healing in 50% and prior disease duration of 10.1 yrs. Of these, 51% had
and partial healing (ulcers £5 mm in no more than 2 seg- previously failed (cid:1)2 anti-TNFs with 29.1%, 69.4%, and
ments) in 82%. Clinical remission (CDAI < 150) at one year 36.4% of pts, respectively. Clinical response at Wk6 was
occurred in 46% patients (39% in remission >3 months off observed in 33.7%/34.3% of the ~6mg/kg/130mg UST grps
steroids). On univariate analysis baseline factors associated vs 21.5% on PBO(p = 0.003, p = 0.002, respectively). Clini-
with steroid free clinical remission at 1 year include colonic cal remission(CDAI < 150) at Wk8 was seen in 20.9%/15.9%
localization (p = 0.006), inflammatory phenotype vs 7.3% on PBO(p < 0.001, p = 0.003, respectively). Clinical
(p = 0.009), high SES-CD (p = 0.005). Age, CRP and early response at Wk8 was seen in 37.8%/33.5% vs 20.2% on PBO
vs delayed HSCTwere not significant. On multivariate analysis (each p £ 0.001). Proportion of pts with 70 pt CDAI
high baseline SES CD was associated with steroid free remis- response at Wk6 was 43.8%/46.1% vs 30.4% on PBO
sion at year 1 (OR 1.21 95%CI 1.03–1.41; p = 0.017). (p = 0.002, p < 0.001, respectively) and at first post-BL
Wk3 visit, 40.6%/38.4% vs 27.1% on PBO(p = 0.001,
Gut2016;7(1):A1–A310 A3
Abstracts
p = 0.009, respectively). Both IV UST induction doses Pfizer, Takeda, Protagonist Therapies, Celgene, Genentech,
resulted in significant improvements in CDAI, IBDQ, CRP, Second Genome, Vertex, Amgen, Merck Sharp Dohme, Jans-
faecal lactoferrin and calprotectin vs PBO. Rates of AEs, SAEs, sen, Nestle, AbbVie, Tigenix, Receptos, Conflict with: Speaker
and infections were similar in the UST&PBO grps. One for AbbVie, Ferring, Shire, Takeda, S. Lee Grant/research sup-
opportunistic infection(listeria meningitis) was reported in the port from: AbbVie Pharmaceuticals UCB Pharma Janssen Phar-
~6mg/kg UST grp. No malignancies, deaths, major adverse maceuticals, Inc. Salix Pharmaceuticals Takeda Pharmaceuticals,
cardiovascular events, or TB occurred in UST-treated pts Inc. Celgene Pharmaceuticals, Inc. Amgen Pharmaceuticals, Inc.
through Wk20. Pfizer Pharmaceuticals, Inc., Consultant for: UCB Pharma
Conclusion In a population of moderate-severe CD pts refrac- Robarts Mesoblast Cornerstones Janssen Pharmaceuticals, Inc.
tory to (cid:1)1 prior TNF-antagonists, IV UST induced clinical Takeda Pharmaceuticals, Inc., P. Desreumaux Grant/research
response and remission and was well-tolerated throughout support from: 1. Ferring, St Prex, Suisse 2. Ferring, Danemark
induction, confirming the previous positive induction data 3. Giuliani SpA, Milano, Italy 4. Lesaffre, Marcq en Baroeul,
from CERTIFI. France 5. Roquette, Lestrem, France 6. Sanofi-Synthelabo,
Paris, France 7. UCB Pharma, Paris, France 8. Yoplait, Paris,
REFERENCE France 9. Omega Pharma, Belgium, Consultant for: 1. Biofor-
1 SandbornWJ,etal.NEnglJMed2012;367:1519–1528. tis, Nantes, France 2. Ferring, St Prex, Suisse 3. Giuliani SpA,
Milano, Italy 4. Roquette, Lestrem, France 5. UCB Pharma,
Disclosure of Interest P. Rutgeerts Consultant for: J&J, Merck,
Paris, France 6. Txcell, Nice, France 7. Lesaffre, Marcq en
UCB, AbbVie, Millenium/Takeda, Genentech/Hoffman
Baroeul, France 8. MSD, France 9. Abbott, France 10. Nor-
LaRoche, Medimmune/AstraZeneca/Amgen, Merck/Serono,
gine, France 11. Genfit, France 12. OmegaPharma Interna-
Bristol Myers Squibb, Robarts, Tillotts Pharma, Conflict with:
tional 13. Ppm, Switzerland 14. Kitozyme, Belgium 15. LFB,
Lectures for J&J, Merck, AbbVie, C. Gasink Shareholder of:
France, Conflict with: Lecture fees: 1. Ferring, Paris, France
Janssen, Employee of: Janssen, M. Blank Employee of: Jans-
2. Ferring, London, UK 3. Shire Pharmaceuticals, USA 4. UCB
sen, Y. Lang Shareholder of: Janssen, Employee of: Janssen, J.
Pharma, Paris, France 5. MSD, France 6. Norgine, France 7.
Johanns Shareholder of: Janssen, Employee of: Janssen, L.-L.
Abbott, France 8. Pileje, France, E. Loftus Jr Grant/research
Gao Shareholder of: Janssen, Employee of: Janssen, B. Sands
support from: Takeda, UCB, Janssen, AbbVie, Genentech, Cel-
Grant/research support from: Janssen, Consultant for: Janssen,
gene, Amgen, Pfizer, Gilead, Receptos, Robarts Clinical Trials,
S. Hanauer Grant/research support from: Janssen, Consultant
Consultant for: Takeda, UCB, Janssen, AbbVie, Genentech,
for: Janssen, Conflict with: Lecturer for Janssen, B. Feagan
Celgene, Theradiag, Seres Therapeutics, Sun Pharmaceuticals,
Grant/research support from: Abbott/AbbVie, Amgen, Astra
Bristol-Myers Squibb, S. Vermeire Grant/research support
Zeneca, Bristol-Myers Squibb (BMS), Janssen Biotech (Cento-
from: Abbvie, MSD, Takeda, Consultant for: Abbvie, MSD,
cor), JnJ/Janssen, Roche/Genentech, Millennium, Pfizer, Recep-
Takeda, Ferring, Genentech/Roche, Shire, Pfizer, Galapagos,
tos, Santarus, Sanofi, Tillotts, UCB Pharma, Consultant for:
Mundipharma, Hospira, Celgene, Second Genome, Janssen,
Abbott/AbbVie, Actogenix, Akros, Albireo Pharma, Amgen,
Conflict with: Lectures: Abbie, MSD, Takeda, Ferring, Falk
Astra Zeneca, Avaxia Biologics Inc., Avir Pharma, Axcan,
Pharma, Hospira, Tillotts, W. Sandborn Grant/research support
Baxter Healthcare Corp., Biogen Idec, Boehringer-Ingelheim,
from: Receptos, Exact Sciences, Amgen, the American College
Bristol-Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen,
of Gastroenterology, Broad Foundation, Prometheus Laborato-
EnGene, Ferring Pharma, Roche/Genentech, GiCare Pharma,
ries, AbbVie, Boehringer Ingelheim, Takeda, Atlantic Pharma-
Gilead, Given Imaging Inc., GSK, Ironwood Pharma, Janssen
ceuticals, Janssen, Bristol-Myers Squibb, Genentech, Pfizer, and
Biotech (Centocor), JnJ/Janssen, Kyowa Kakko Kirin Co Ltd.,
Nutrition Science Partners, Conflict with: Personal fees from
Lexicon, Lilly, Lycera BioTech, Merck, Mesoblast Pharma, Mil-
Receptos, Prometheus Laboratories, AbbVie, Boehringer Ingel-
lennium, Nektar, Nestles, Novonordisk, Pfizer, Prometheus
heim, Takeda, Atlantic Pharmaceuticals, Janssen, Bristol-Myers
Therapeutics and Diagnostics, Protagonist, Receptos, Salix
Squibb, Genentech, Pfizer, Nutrition Science Partners, Kyowa
Pharma, Serono, Shire, Sigmoid Pharma, Synergy Pharma Inc.,
Hakko Kirin, Millennium Pharmaceuticals, Celgene Cellular
Takeda, Teva Pharma, TiGenix, Tillotts, UCB Pharma, Vertex
Therapeutics, Santarus, Salix Pharmaceuticals, Catabasis Phar-
Pharma, VHsquared Ltd., Warner-Chilcott, Wyeth, Zealand,
maceuticals, Vertex Pharmaceuticals, Warner Chilcott, Gilead
Zyngenia, Speaker bureau with: Abbott/AbbVie, JnJ/Janssen,
Sciences, Cosmo Pharmaceuticals, Ferring Pharmaceuticals, Sig-
Takeda, Warner-Chilcott, UCB Pharma, Conflict with: Patent
moid Biotechnologies, Tillotts Pharma, Am Pharma BV, Dr.
holder; Member Scientific Advisory board, Abbott/AbbVie,
August Wolff, Avaxia Biologics, Zyngenia, Ironwood Pharma-
Amgen, Astra Zeneca, Avaxia Biologics Inc., Bristol-Myers
ceuticals, Index Pharmaceuticals, Nestle, Lexicon Pharmaceuti-
Squibb, Celgene, Centocor Inc., Elan/Biogen, Ferring, JnJ/Jans-
cals, UCB Pharma, Orexigen, Luitpold Pharmaceuticals, Baxter
sen, Merck, Nestles, Novartis, Novonordisk, Pfizer, Prome-
Healthcare, Ferring Research Institute, Amgen, Novo Nordisk,
theus Laboratories, Protagonist, Salix Pharma, Takeda, Teva,
Mesoblast Inc., Shire, Ardelyx Inc., Actavis, Seattle Genetics,
TiGenix, Tillotts Pharma AG, UCB Pharma; Member, Board
MedImmune (AstraZeneca), Actogenix NV, Lipid Therapeutics
of Directors Officer – Robarts Clinical Trials Inc, S. Targan
Gmbh, Eisai, Qu Biologics, Toray Industries Inc., Teva Phar-
Grant/research support from: Cedars-Sinai Medical Centre,
maceuticals, Eli Lilly, Chiasma, TiGenix, Adherion Therapeu-
Consultant for: Janssen, NuMedii, Inc., Conflict with: Advi-
tics, Immune Pharmaceuticals, Celgene, Arena Pharmaceuticals,
sory board for the Seaver Foundation; Scientific Advisory
Ambrx Inc., Akros Pharma, Vascular Biogenics, Theradiag, For-
Board Member Symbiotix, S. Ghosh Grant/research support
ward Pharma, Regeneron, Galapagos, Seres Health, Ritter
from: Abbvie, Conflict with: International Steering Commit-
Pharmaceuticals, Theravance, Palatin, Biogen, and the Univer-
tees: Janssen, Abbvie, Pfizer, Receptos, BMS, Aerpio; Advisory
sity of Western Ontario (owner of Robarts Clinical Trials);
Committees: Takeda, Abbvie, Janssen, Pfizer, Allergan, W. de
non-financial support from Receptos
Villiers Conflict with: member of steering committee, active
participant as investigator, J.-F. Colombel Consultant for:
A4 Gut2016;7(1):A1–A310
Abstracts
OC-006 ANTI-TNFTHERAPYALTERSDENDRITICCELL pattern recognition receptors) and intra-cellular on-going DC
TRAFFICKINGANDCYTOKINEPRODUCTIONIN cytokine production were determined.
CROHN’SDISEASE Results Treatment with anti-TNFa resulted in an alteration of
the phenotype of mDC in Crohn’s disease. The gut homing
1,2PAHendy*,1DReddi,3DBarnardo,1LDurant,1ANoble,1PBhat,1NEnglish,1SCKnight,
1,2ALHart.1APRG,ImperialCollege;2Gastroenterology,StMark’sHospital,London,UK; phenotype of mDC in Crohn’s disease was down-regulated
3ResearchUnit(7thfloor),HospitalUniversitariodelaPrincesa,Madrid,Spain with anti-TNFa (CLA(cid:3)b7+p = 0.0056 Fig A) whilst the non-
tissue specific phenotype (CLA+b7+p = 0.0026 Fig not
10.1136/gutjnl-2016-312388.6 shown) and skin homing phenotype were up-regulated
(CLA+b7(cid:3) p = 0.0055 Fig B).
Introduction Dendritic cells (DC) act as a bridge between the Production of TNFa and IL-6 by mDC and pDC respec-
innate and adaptive immune system, sensing and presenting tively, shown to be increased in Crohn’s disease, was signifi-
antigen to lymphocytes and mounting either a tolerogenic or cantly reduced by anti-TNFa therapy (p = 0.033 and
inflammatory response. They are able to imprint homing p = 0.014 Fig C and Fig D respectively). Production of IL-10
capacity on T-cells, directing them into specific tissues. Abnor- was increased following therapy (p = 0.051). There were no
mal DC function contributes to the pathogenesis of Crohn’s changes in IL-12, IL-23 and IFN-a production. Significant
disease and thus DC represent a potential therapeutic target. improvements in clinical markers were observed following
In this study we have investigated the effect of anti-TNFa treatment.
therapy on circulating DC of patients with Crohn’s disease. Conclusion The reversal of inflammatory DC phenotype and
Methods We recruited 13 consecutive patients with active function by anti-TNFa further highlights the potential role
luminal Crohn’s due to start anti-TNFa therapy. Clinical this antigen presenting cell may play in the pathogenesis of
parameters including the Harvey-Bradshaw index, C-reactive Crohn’s disease. DC are a promising therapeutic target in
protein and faecal calprotectin were measured. Peripheral Crohn’s because they can be modulated to express a non-gut
blood mononuclear cells were isolated from each patient homing phenotype and direct T cells away from the gut and
immediately before and six weeks after commencing anti- promote tolerogenic effects. The increase in skin homing DC
TNFa therapy. At both time points flow cytometry was per- following anti-TNFa treatment may explain the high rate of
formed to assess DC phenotype and function. We also ana- skin complications. The reduction in gut homing DC may
lysed subsets of DC: myeloid (mDC, CD11c+CD123(cid:3)) and offer an explanation for reduced treatment success with vedo-
plasmacytoid (pDC, CD11c(cid:3)CD123+). Expression of pheno- lizumab (a4b7 blocker) after previous anti-TNFa therapy
typic markers (including maturation and homing markers and (reduction of vedolizumab treatment target).
DisclosureofInterestNone Declared
AbstractOC-006Figure1 A–D:mDCexpression ofCLA-/b7*(A),CLA*/b7-(B)homingmarkers.ProductionofTNF-a(c)andIL(D)bymDCand
pDCrespectively.
Gut2016;7(1):A1–A310 A5
Abstracts
OC-007 AMULTICENTER,DOUBLE-BLIND,PLACEBO(PBO)- Conclusion IV UST induced clinical response & remission in
CONTROLLEDPH3STUDYOFUSTEKINUMAB(UST), pts with moderate-severe CD not previously failing anti-TNFs
AHUMANMABTOIL-12/23P40,INPTSWITH & was well-tolerated through induction.
MODERATELY-SEVERELYACTIVECROHN’SDISEASE
(CD)WHOARENAÏVEORNOTREFRACTORYTOANTI-
REFERENCE
TNFA:UNITI-2 1 SandbornWJ,etal.NEnglJMed2012;367:1519–1528.
1BFeagan,2CGasink*,2YLang,2JRFriedman,2JJohanns,2L-LGao,3BSands,4SHanauer,
5PRutgeerts,6STargan,7SGhosh,8WdeVilliers,3J-FColombel,9ZTulassay,10USeidler, Disclosure of Interest B. Feagan Grant/research support from:
11WJSandborn.1RobartsResInst,London,Canada;2JanssenR&D,SpringHouse;3MtSinai Abbott/AbbVie, Amgen, Astra Zeneca, Bristol-Myers Squibb
Med Ctr, New York; 4Northwestern U, Chicago, United States; 5U Hosp Gasthuisberg, (BMS), Janssen Biotech (Centocor), JnJ/Janssen, Roche/Genen-
Leuven,Belgium;6Cedars-SinaiMedCtr,LosAngeles,UnitedStates;7UCalgary,Calgary, tech, Millennium, Pfizer, Receptos, Santarus, Sanofi, Tillotts,
Canada;8UCapeTown,CapeTown,SouthAfrica;9SemmelweisU,Budapest,Hungary; UCB Pharma, Consultant for: Abbott/AbbVie, Actogenix,
10HannoverMedSchool,Hannover,Germany;11UCSD,LaJolla,UnitedStates
Akros, Albireo Pharma, Amgen, Astra Zeneca, Avaxia Biologics
Inc., Avir Pharma, Axcan, Baxter Healthcare Corp., Biogen
10.1136/gutjnl-2016-312388.7
Idec, Boehringer-Ingelheim, Bristol-Myers Squibb, Calypso Bio-
Introduction InthePh2bCERTIFIstudy,asingleintravenous(IV) tech, Celgene, Elan/Biogen, EnGene, Ferring Pharma, Roche/
USTinductiondosewaseffective&safeinCDptspreviouslyfail- Genentech, GiCare Pharma, Gilead, Given Imaging Inc., GSK,
inganti-TNFs,1butefficacyinptsonlyfailingconventionaltherapy Ironwood Pharma, Janssen Biotech (Centocor), JnJ/Janssen,
isunknown.Weevaluated2IVUSTinductiondoseregimensina Kyowa Kakko Kirin Co Ltd., Lexicon, Lilly, Lycera BioTech,
CDpopulationnotrefractorytoanti-TNFs. Merck, Mesoblast Pharma, Millennium, Nektar, Nestles, Novo-
Methods Pts with moderate-severely active CD (CDAI 220–450) nordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Pro-
who failed conventional therapy but were not refractory to anti- tagonist, Receptos, Salix Pharma, Serono, Shire, Sigmoid
TNFswererandomised toasingle dose ofIVPBO,UST 130mg, Pharma, Synergy Pharma Inc., Takeda, Teva Pharma, TiGenix,
or weight-based tiered UST dosing ~6 mg/kg. Primary endpoint Tillotts, UCB Pharma, Vertex Pharma, VHsquared Ltd.,
was clinical response at Wk6 (reduction in CDAI score of (cid:1)100 Warner-Chilcott, Wyeth, Zealand, Zyngenia, Speaker bureau
pts). At Wk8,pts transitionedtoIM-UNITI maintenancestudy or with: Abbott/AbbVie, JnJ/Janssen, Takeda, Warner-Chilcott,
hadsafetyfollow-upthroughWk20. UCB Pharma, Conflict with: Patent holder; Member Scientific
Results Of 628 pts randomised, median disease duration was 6.4 Advisory board, Abbott/AbbVie, Amgen, Astra Zeneca, Avaxia
yrs;baseline(BL)meanCDAIwas303;39%&35%werereceiving Biologics Inc., Bristol-Myers Squibb, Celgene, Centocor Inc.,
steroids&immunomodulators,respectivelyatBL;69%werenaïve Elan/Biogen, Ferring, JnJ/Janssen, Merck, Nestles, Novartis,
to anti-TNFs. At Wk6, 55.5% & 51.7% in ~6mg/kg & 130mg Novonordisk, Pfizer, Prometheus Laboratories, Protagonist,
USTgrpswereinclinicalresponsevs28.7%PBO(p<0.001).At Salix Pharma, Takeda, Teva, TiGenix, Tillotts Pharma AG,
Wk8, 40.2% & 30.6% of pts in ~6mg/kg & 130mg UST grps UCB Pharma; Member, Board of Directors Officer – Robarts
were in clinical remission vs 19.6% PBO (p £ 0.009). Both UST Clinical Trials Inc, C. Gasink Shareholder of: Janssen,
doses showed significant improvements vs PBO in CDAI, IBDQ, Employee of: Janssen, Y. Lang Shareholder of: Janssen,
CRP,&faecallactoferrin&calprotectin.ProportionsofAEs,SAEs, Employee of: Janssen, J. Friedman Shareholder of: Janssen,
& infections were similar in UST & PBO grps. No malignancies, Employee of: Janssen, J. Johanns Shareholder of: Janssen,
deaths,opportunisticinfectionsorTBoccurredinUST-treatedpts. Employee of: Janssen, L.-L. Gao Shareholder of: Janssen,
Employee of: Janssen, B. Sands Grant/research support from:
Janssen, Consultant for: Janssen, S. Hanauer Grant/research
AbstractOC-007Table1
support from: Janssen, Consultant for: Janssen, Conflict with:
PBO UST130mg UST~6mg/kgcc Lecturer for Janssen, P. Rutgeerts Grant/research support from:
(n=209) (n=209) (n=209) J&J, Merck, UCB, AbbVie, Consultant for: J&J, Merck, UCB,
ClinicalResponsea AbbVie, Millenium/Takeda, Genentech/Hoffman LaRoche,
Wk3 45(21.5) 68(32.5) 81(38.8) Medimmune/AstraZeneca/Amgen, Merck/Serono, Bristol Myers
p=0.010 p<0.001 Squibb, Robarts, Tillotts Pharma, Conflict with: Lectures for
*Wk6 60(28.7) 108(51.7) 116(55.5) J&J, Merck, AbbVie, S. Targan Grant/research support from:
Delta=23% Delta=26.8% Cedars-Sinai Medical Centre, Consultant for: Janssen, NuMe-
p<0.001 p<0.001 dii, Inc., Conflict with: Advisory board for the Seaver Founda-
Wk8 67(32.1) 99(47.4) 121(57.9) tion; Scientific Advisory Board Member Symbiotix, S. Ghosh
p<0.001 p<0.001 Grant/research support from: Abbvie, Conflict with: Interna-
ClinicalRemissionb tional Steering Committees: Janssen, Abbvie, Pfizer, Receptos,
Wk3 24(11.5) 33(15.8) 48(23.0) BMS, Aerpio; Advisory Committees: Takeda, Abbvie, Janssen,
p=0.199 p=0.002 Pfizer, Allergan, W. de Villiers Conflict with: member of steer-
Wk6 37(17.7) 60(28.7) 73(34.9) ing committee, active participant as investigator, J.-F. Colom-
p=0.007 p<0.001 bel Consultant for: Pfizer, Takeda, Protagonist Therapies,
Wk8 41(19.6) 64(30.6) 84(40.2) Celgene, Genentech, Second Genome, Vertex, Amgen, Merck
Delta=11.0% Delta=20.6% Sharp Dohme, Janssen, Nestle, AbbVie, Tigenix, Receptos,
p=0.009 p<0.001 Conflict with: Speaker for AbbVie, Ferring, Shire, Takeda, Z.
Tulassay: None Declared, U. Seidler Conflict with: Local con-
N(%);a(cid:1)100ptreductioninCDAI;bCDAI<150;cweight-rangebasedUSTdoses~6mg/
tinuing medical education seminars for MSD, W. Sandborn
kg: 260mg (weight £55kg), 390mg (weight >55kg and £85kg), 520mg (weight
Grant/research support from: Receptos, Exact Sciences,
>85kg);*primaryendpoint
Amgen, the American College of Gastroenterology, Broad
A6 Gut2016;7(1):A1–A310
Abstracts
Foundation, Prometheus Laboratories, AbbVie, Boehringer months (including 3/4 withdrawn patients) was RFA: 15.6%
Ingelheim, Takeda, Atlantic Pharmaceuticals, Janssen, Bristol- & APC: 12.9% (OR 1.25; 95%CI 0.3–5.17). Endoscopy dura-
Myers Squibb, Genentech, Pfizer, and Nutrition Science Part- tion was longer for RFA especially at 2 months (Median,
ners, Conflict with: Personal fees from Receptos, Prometheus mean (SD) mins= RFA: 30.0, 38.0 (25.7) and APC 23.0,
Laboratories, AbbVie, Boehringer Ingelheim, Takeda, Atlantic 27.2 (15.8)). Residual BE at 12 months occurred in 38.7%
Pharmaceuticals, Janssen, Bristol-Myers Squibb, Genentech, (RFA) & 31% (APC). Median, mean (SD) residual BE were:
Pfizer, Nutrition Science Partners, Kyowa Hakko Kirin, Millen- RFA 0, 1.3 (2.6)cm & APC 1.0, 1.7 (2.6)cm, slightly favour-
nium Pharmaceuticals, Celgene Cellular Therapeutics, Santarus, ing RFA for BE >5 cm. AEs for APC: 2 dysphagia/strictures,
Salix Pharmaceuticals, Catabasis Pharmaceuticals, Vertex Phar- 5 bleeds & for RFA: 1 perforation due to ER, 2 dysphagia/
maceuticals, Warner Chilcott, Gilead Sciences, Cosmo Pharma- strictures, 1 syncope, 4 bleeds. There were no difference in
ceuticals, Ferring Pharmaceuticals, Sigmoid Biotechnologies, QL scores. Exit histology showed EAC (1 RFA; 0 APC),
Tillotts Pharma, Am Pharma BV, Dr. August Wolff, Avaxia Bio- buried glands (1 RFA;3 APC), HGD (3 RFA, 2 APC). Sample
logics, Zyngenia, Ironwood Pharmaceuticals, Index Pharma- size for a non-inferiority trial comparing APC to RFA (with a
ceuticals, Nestle, Lexicon Pharmaceuticals, UCB Pharma, non-inferiority margin of 6%) would be 461 subjects/arm.
Orexigen, Luitpold Pharmaceuticals, Baxter Healthcare, Ferring Conclusion Patients with BE are willing to enrol & remain in
Research Institute, Amgen, Novo Nordisk, Mesoblast Inc., studies comparing RFA & APC over 12 months. This feasibil-
Shire, Ardelyx Inc., Actavis, Seattle Genetics, MedImmune ity study suggests no difference in outcome between APC &
(AstraZeneca), Actogenix NV, Lipid Therapeutics Gmbh, Eisai, RFA. A fully powered RCT requires a large sample size to
Qu Biologics, Toray Industries Inc., Teva Pharmaceuticals, Eli show non-inferiority of APC compared to RFA. (NIHR RfPB
Lilly, Chiasma, TiGenix, Adherion Therapeutics, Immune Phar- Grant No PB-PG-0711-25066)
maceuticals, Celgene, Arena Pharmaceuticals, Ambrx Inc.,
Akros Pharma, Vascular Biogenics, Theradiag, Forward REFERENCES
1 Pechetal.Gut2008;57:1200–6.
Pharma, Regeneron, Galapagos, Seres Health, Ritter Pharma-
2 Shaheenetal.NEJM2009;360:2277–88.
ceuticals, Theravance, Palatin, Biogen, and the University of 3 Manneretal.Endoscopy2014;46:6–12.
Western Ontario (owner of Robarts Clinical Trials); non-finan-
cial support from Receptos
Disclosure of Interest M. F. Peerally: None Declared, H. Barr:
None Declared, L. Lovat: None Declared, P. Bhandari: None
Declared, K. Ragunath Conflict with: Speaker Honoraria, Edu-
OC-008 RESULTSOFAFEASIBILITYSTUDYCOMPARINGAPC cational grants, Consultancy, Research grants and support:
WITHRFAAFTERENDOSCOPICRESECTIONOFEARLY Olympus, Pentax, Cook, Boston Scientific, ERBE, Medtronics/
NEOPLASIAINBARRETT’SOESOPHAGUS:THEBRIDE Covidien, Astra Zeneca, Ferring, H. Smart: None Declared, R.
STUDY(NCT01733719) Harrison: None Declared, C. Stokes: None Declared, J. Deca-
estecker: None Declared
1MF Peerally, 2H Barr, 3LB Lovat, 4P Bhandari, 5K Ragunath, 6H Smart, 1R Harrison,
2C Stokes, 1J Decaestecker*. 1Univ Hosp Leicester, Leicester; 2Gloucs Royal Hosp,
Gloucester; 3Univ College London, London; 4QA Hosp, Portsmouth; 5Nottingham Univ
Hosp,Nottingham;6TheRoyalLiverpoolHosp,Liverpool,UK
OC-009 SPYGLASSDS™CHOLANGIOSCOPYFORDIFFICULT
10.1136/gutjnl-2016-312388.8 STONES:EARLYEXPERIENCEOFTWOUKCENTRES
1NLBekkali*,2RSturgess,2LDwyer,1SDirekze,1GJWebster.1HPB,UCLH,London;2HPB,
Introduction Endoscopic therapy is safe and effective for Bar-
Aintree,Liverpool,UK
rett’s Oesophagus (BE) patients with high grade dysplasia
(HGD) or early (T1A) adenocarcinoma (EAC). Endoscopic
10.1136/gutjnl-2016-312388.9
resection (ER) removes visible neoplasia but metachronous
lesions occur in up to 30%.1 RCTs of RFA2 & APC3 show Introduction Endoscopic clearance of bile duct stones is
reduced recurrence but the 2 techniques have not been com- achievable in >90% with conventional ERCP (ASGE 2015).
pared. We aim to test the feasibility of recruiting & retaining Additional techniques may be necessary for those patients with
up to 100 BE patients with HGD or T1A EAC to RFA or difficult stones, which may be due to stone location, size, or
APC after ER. number. Cholangioscopy and intraductal lithotripsy may have
Methods Patients with BE & HGD or T1A EAC confirmed a specific role in treating difficult stones. The Spyglass DS™
by ER (single tongues £2cm excluded) were recruited over 1 peroral cholangioscopy system was introduced in mid-2015,
year in 6 centres, stratified into 3 groups as per BE length and here we report our early experience with this technique.
(<5cm, 5–10cm, >10cm) & randomised to 4 interventions Methods Spyglass DS cholangioscopy was available in the UK
with RFA or APC every 2 months. All received high dose from May 2015. Cases referred to our 2 centres were assessed
twice-daily PPIs. ER was allowed for further visible lesions. within a specialist HPB multidisciplinary meeting, and all cases
Exit endoscopy with biopsies was at 12 months. Persistence of deemed appropriate for Spyglass DS were prospectively fol-
BE, recruitment, retention & adverse events(AEs) were lowed. Patient demographics, indication for cholangioscopy,
recorded. Quality of life (QL) was assessed with EQ-5D, technical outcome and complications were recorded.
EORTC QLQ-C30 & OES18 at 0, 6 & 12 months. Results Eight-four patients (54% female, median age 61 years
Results 171 patients were screened. 41.5% were excluded & (range 25–90)) underwent ERCP with plan for cholangioscopy.
14% declined participation. 76 patients (84.2% males, mean Indications were stones (83%), strictures (14%) and other
age 69.7) were randomised to receive RFA (36) or APC (40) (3%). The stones were extrahepatic (62%), intrahepatic (15%),
and stratified according to BE length (<5 cm (27); 5–10cm cystic duct (15%), and intra + extrahepatic (8%). The total
(44); >10cm(4)). 13 withdrew, 4 for more advanced cancer number of stones was <5 in 58%, 5–10 in 18%, 11–15 in
and 9 for other reasons. Persistence of HGD/T1 EAC at 12 9%, 16–20 in 9% and >20 stones in 6%. The 70 patients
Gut2016;7(1):A1–A310 A7