S276 Poster presentations

P500Efficacy and safety of granulocyte, monocyte/macrophageadsorptive apheresis in steroid-dependent active UC withinsufficient response or intolerance to immunosuppressantsand/or biological therapies (the ART trial): Results at12 weeksA. Dignass1 *, A. Akbar2, B. Bonaz3. 1Agaplesion MarkusHospital, Department of Medicine I, Frankfurt, Germany,2St Mark’s Hospital, Dept. of Medicine, Harrow, UnitedKingdom, 3CHU de Grenoble, Clinique Universitaired’Hepato-Gastroenterologie, Grenoble, France

Background: The current medical treatment options forpatients with steroid-dependent, active ulcerative colitis (UC)with insufficient response or intolerance to immunosuppres-sants (IS) and/or biologicals are limited and not evidence-based. The clinical use of Granulocyte, Monocyte/MacrophageAdsorptive (GMA) apheresis with Adacolumn® has previouslyindicated a potential benefit in this specific subgroupof UC patients. The present study intended to generatefurther clinical data to document efficacy and to identifysubpopulations of this difficult-to-treat UC population thatwould benefit from GMA apheresis.Methods: This was an uncontrolled, open-label, multicentertrial conducted in the UK, France and Germany (ART,NCT01481142). Consecutive eligible patients (18 75 years)with steroid-dependent active UC with a Rachmilewitz (CAI)index �6 and an Endoscopic Activity Index (EAI) �4, andinsufficient response or intolerance to IS and/or biologicalswere included. Patients received at least 5 weekly GMAaphereses. Evaluation visits were planned at Week 12, 24 and48. The primary endpoint was the remission rate (CAI �4) atWeek 12 in the Intention-to-treat (ITT) population.Results: We report interim results from the 12 Week visit. TheITT population comprised 84 enrolled and treated patients atcutoff date. At Week 12, 33 (39.3%) subjects had achievedremission. Out of 30 patients with prior failure of IS and/orbiologicals, the remission rate was 30%. Secondary efficacyparameters were clinical response defined as a reduction inCAI of �3, and steroid-free remission and response. 47 patients(55.9%) achieved response; steroid-free remission was reachedby in 23% and steroid-free response was seen in 36% of thesubjects. In clinical remitters, EAI dropped from 8.2 to 4.4; inclinical responders the EAI decreased from 8.6 to 5.3. Quality oflife improved in parallel. The majority of Adverse Events (AEs)were of mild or moderate intensity. Six (7.1%) of 85 subjectsin the Safety Population experienced serious adverse events(SAEs), all occurring during the treatment-emergent period;however, none of those SAEs was considered related to studytreatment. No new safety signals were seen.Conclusions: This study describes a larger cohort of steroid-dependent active UC patients with intolerance to IS and/or

biologicals treated with GMA apheresis. GMA apheresis withAdacolumn® showed benefit in more than 50% of patientswith moderate to severe, active, steroid-dependent UC andinsufficient response or intolerance to IS and/or biologicalagents. Further controlled studies are needed to confirm thesedata.This trial was sponsored by Otsuka Pharmaceuticals Europe,Ltd.

P501Effects of continued vedolizumab therapy forulcerative colitis in week 6 induction therapynonresponders

B. Feagan1 *, W.J. Sandborn2,3, M. Smyth4, S. Sankoh5,A. Parikh6, I. Fox7. 1Western University/Robarts ResearchInstitute, Robarts Clinical Trials Inc, London, Ontario,Canada, 2University of California, San Diego, Divisionof Gastroenterology, La Jolla, United States, 3RobartsClinical Trials Inc., Robarts Research Institute, WesternUniversity, London, Ontario, Canada, 4Takeda DevelopmentCentre (Europe) Ltd, General Medicine/GI/Renal, London,United Kingdom, 5Takeda Pharmaceuticals InternationalCompany, Global Statistics, Cambridge, United States,6Takeda Pharmaceuticals International, Inc., GeneralMedicine, Deerfield, United States, 7Takeda PharmaceuticalsInternational Company, Clinical Development, Cambridge,United States

Background: Vedolizumab (VDZ) is a gut-selective, humanized,anti-a4b7 integrin monoclonal antibody that was evaluated fortreating ulcerative colitis (UC). In the GEMINI 1 trial, 47.1% ofpatients had a clinical response to VDZ induction therapy atweek (wk) 6. Here the efficacy of continuing VDZ therapy isevaluated in wk 6 nonresponders.Methods: GEMINI 1 (NCT00783718) patients were randomlyassigned to receive placebo (PBO) or VDZ 300 mg (cohort 1)or assigned to receive open-label VDZ (cohort 2) at wks 0and 2. Those who did not respond to VDZ at wk 6 receivedopen-label VDZ every 4 wks (Q4W) during maintenance, andall PBO-treated patients continued on PBO. Clinical response(reduction in partial Mayo Clinic score [MCS] of �2 pointsand decrease of �25%, with a reduction in rectal bleedingsubscore of �1 point or a rectal bleeding subscore of 0 or 1)and clinical remission (partial MCS of �2 points and no subscore>1 point) were assessed in wk 6 nonresponders at wks 10 and 14(prespecified) and at wk 52 (post hoc). Wk 52 post hoc analyseswere also performed for mucosal healing (Mayo Clinic scaleendoscopic subscore of 0 or 1) in wk 6 nonresponders and forefficacy end points in wk 6 nonresponders who had clinicalresponse at wk 10 or 14.Results: At baseline, the median duration of UC in VDZwk 6 nonresponders (4.6 years) was similar to that of wk 6

Table (abstract P501)

End points in VDZ combined (Induction cohorts 1 and 2) PBO (Induction cohort 1)Wk 6 Nonresponders a Wk 10 Wk 14 Wk 52 Wk 10 Wk 14 Wk 52

All Wk 10responders

Wk 14responders

All Wk 10responders

Wk 14responders

n = 322 n = 322 n = 322 n = 102 n = 126 n = 82 n = 82 n = 82 n = 12 n = 17

Clinical response b 31.7 39.1 28.9 51 54 14.6 20.7 8.5 33 4195% CI (26.6, 36.8) (33.8, 44.5) (23.9, 33.8) (41.3, 60.7) (45.3, 62.7) (7.0, 22.3) (12.0, 29.5) (2.5, 14.6) (6.7, 60.0) (17.8, 64.6)

Clinical remission c 11.8 14.6 16.1 34 35 4.9 9.8 4.9 25 2495% CI (8.5, 15.8) (10.7, 18.5) (12.1, 20.2) (25.1, 43.5) (26.6, 43.2) (1.3, 12.0) (3.3, 16.2) (0.2, 9.5) (0.5, 49.5) (3.4, 43.7)

Mucosal healing NC NC 23.6 45 44 NC NC 8.5 33 3595% CI (19.0, 28.2) (35.4, 54.8) (35.0, 52.3) (2.5, 14.6) (6.7, 60.0) (12.6, 58.0)

NC, not collected; PBO, placebo; VDZ, vedolizumab.a Data are shown as percentages of patients.b At week 52, clinical response was defined as a reduction in complete Mayo Clinic score of �3 points and a decrease of �30% from the baseline score, withan accompanying reduction in rectal bleeding subscore of �1 point or absolute rectal bleeding subscore of �1 point.c At week 52, clinical remission was defined as a complete Mayo Clinic score of �2 points and no subscore >1 point.

Clinical: Therapy & observation S277

responders. Median baseline complete MCS was higher in VDZwk 6 nonresponders (9.0) than in wk 6 responders (8.0). Rate ofprevious tumour necrosis factor antagonist failure was higheramong wk 6 nonresponders (51%) than among wk 6 responders(32%). Proportions of wk 6 nonresponders who had clinicalresponse, clinical remission, or mucosal healing at wk 10, 14,and 52 were greater with VDZ than with PBO (Table). For bothVDZ and PBO, proportions of wk 6 nonresponders who hadclinical response, clinical remission, or mucosal healing at wk52 were similar between those who responded at wk 10 andthose who responded at wk 14; small numbers of PBO-treatedpatients in these subgroups limit this analysis.Conclusions: Among patients with UC who did respond to VDZinduction therapy at wk 6, those who continued on VDZ Q4Whad higher rates of clinical response and remission (wks 10, 14,and 52) and of mucosal healing (wk 52) than did those whoreceived PBO.

P502Effect of immunosuppressive treatment in the efficacyof Hepatitis B vaccine in patients with inflammatory boweldiseaseJ. Santos-Antunes*, P. Andrade, S. Rodrigues, F. Magro,S. Lopes, G. Macedo. Centro Hospitalar Sao Joao,Gastroenterology, Porto, Portugal

Aim: To assess the timing of Hepatitis B vaccination in ourinstitution and to study its efficacy, measured by the productionof anti-HBs antibodies, in a cohort of patients with IBD underinfliximab and/or azathioprine. Vaccination was consideredefficient when anti-HBs antibody levels exceeded 10 UI/L.Results: We identified 217 patients with IBD under infliximabwho were vaccinated for Hepatitis B, 172 (79%) with Crohn’sDisease and the remaining with Ulcerative Colitis; 114 patients(53%) were male and mean age was 33±11 years. Overall, HBVvaccine was successful in 164 (76%) patients; 43% had anti-bodies titers above 100 UI/L. Only 14 patients were vaccinatedafter infliximab and, of them, only 2 had antibodies above10 UI/L. In contrast, vaccination was efficient in 82% of thepatients vaccinated before infliximab (p < 0.001). Median levelsof anti-HBs antibodies in patients vaccinated after and beforeinfliximab were 1 UI/L (Interquartile Range (IQR) 0 3 UI/L) and84 UI/L (IQR 15 395 UI/L) respectively (p < 0.001). Among thepatients vaccinated before the beginning of infliximab, 88% ofthose vaccinated before azathioprine developed antibodies, incontrast to 55% who were under azathioprine; this differencewas significant even in multivariate analysis (p = 0.03). Meanage was similar in those who did or did not respond to thevaccine (p = 0.141).Conclusions: Our Hepatitis B vaccination policy in thispopulation is very successful, since the vast majority is beingvaccinated before starting infliximab, therefore achieving goodresponse rates. This is of major importance, as observed inthe poor immunization capability of the vaccine in thosealready under anti-TNF. In contrast to previous reports, ourdata suggests that azathioprine can also influence negativelythe immune response to HBV vaccine.

P503Effectiveness of infliximab as remission-induction therapyin patients with active ulcerative colitisK. Yokoyama*, K. Kawagishi, S. Ooka, M. Mukae, M. Sada,K. Kobayashi, W. Koizumi. Kitasato University School ofMedicine, Gastroenterology, Sagamihara, Japan

Background and Objectives: In Japan, about 3 years haveelapsed since infliximab (IFX) was approved for the treatmentof ulcerative colitis (UC). However, many factors, such as theoptimal timing of treatment and the positioning of IFX amongother drugs, remain unclear. We retrospectively studied theeffectiveness of remission-induction therapy with IFX.

tgP>Subjects: The study group comprised 28 patients whoreceived induction therapy with IFX in our hospital.Methods: Partial Mayo scores (pMS; maximum, 9 points)were used to evaluate treatment effectiveness for clinicalsymptoms. Remission was defined as a pMS of �2 plus arectal bleeding score of 0 or 1. Improvement was defined asa pMS of �2 with a �30% decrease plus a rectal bleedingscore of 0 or 1. No change was defined as the same pMS ora decrease of �1. Exacerbation was defined as a pMS higherthat before treatment.Variables: The following variables were assessed: (1) treatmentoutcomes in all patients who received IFX; (2) a comparisonof treatment effectiveness among steroid-dependent patients(n = 14), steroid-resistant patients (n = 5), and steroid non-users(n = 9); and (3) adverse reactions.Results: Outcomes: (1) The pMS in the study group as a wholewas 6.5 at the start of treatment, 3.6 at week 2, 1.8 atweek 8, and 1.3 at week 14. The remission/response ratewas 65% at week 2, 72% at week 8, and 88% at week 14.(2) The pMS at the start of treatment with IFX was 5.7 insteroid-dependent patients, 7.7 in steroid-resistant patients,and 7.2 in steroid non-users, with no significant differences.The pMS at week 14 had decreased to 2.3 in steroid-dependent patients, 0 in steroid-resistant patients, and 0.4 insteroid non-users (p < 0.01). (3) The remission/response rate2 weeks after treatment with IFX was 46% in steroid-dependentpatients, 100% in steroid-resistant patients, and 75% insteroid non-users, indicating that steroid-resistant patientsand steroid non-users promptly responded to treatment.At 14 weeks the remission/response rate was 77% in steroid-dependent patients, 100% in steroid-resistant patients and88% in steroid non-users. (4) Surgery was performed in 3patients. The reason for surgery was no change in symptomsin the steroid-dependent patients and massive bleeding in thesteroid-resistant patient. (5) Adverse reactions occurred in 12patients (42%). Serious adverse included Pneumocystis cariniipneumonia in 1 patient, sepsis in 4, and lupus syndrome in 3.Conclusions: The remission-induction rate was about 72% atweek 14 of treatment with IFX in patients with active UC.IFX therapy was effective even in steroid non-users and shouldtherefore be considered as a treatment option for UC in thefuture.

P504Effectiveness and adverse events of azathioprine ininflammatory bowel disease: 9-year follow-up study

I. Guerra1, A. Algaba1 *, A. Serrano2, C. Aullo3, D. Alcalde1,M. de Lucas1, D. Bonillo1, A. Zapatero4, F. Bermejo1. 1HospitalUniversitario de Fuenlabrada, Gastroenterology, Madrid,Spain, 2Hospital Universitario de Fuenlabrada, Surgery,Madrid, Spain, 3Hospital Universitario de Fuenlabrada,Radiology, Madrid, Spain, 4Hospital Universitario deFuenlabrada, Internal Medicine, Madrid, Spain

Background: Thiopurines are an inflammatory bowel disease(IBD) useful therapy although adverse events (AE) limit theiruse. Our aims were to evaluate the long-term effectivenessof azathioprine (AZA) in IBD and to determinate the AE,their incidence and the potential relationship of them withthiopurine methyltransferase (TPMT) activity.Methods: We included all IBD patients treated with AZA in ourhospital from June 2004 to May 2013. Epidemiological, clinicaland analytical data were prospectively recorded. TPMT activitywas measured by a radiochemical method.Results: 273 consecutive IBD patients (212 Crohn’s dis-ease (CD), 57 ulcerative colitis (UC), 4 unclassified colitis)starting treatment with AZA were included. Mean age was42±13 years, 50% male, 40% smokers. Indications: 78%steroid-dependence, 10.8% fistulizing CD, 4.8% post-resectionprophylaxis of recurrence, 3% steroid-refractoriness and 3.4%