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s1.49 [1.34-1.79]) and UC (p=3.87 x 10-2, OR 1.31 [1.02-1.68]). Moreover, the PTPN2SNP rs7234029 demonstrated a significant association with susceptibility to CD (p=1.30 x10-3; OR 1.35 [1.13-1.62]) and a trend towards association with UC (p=7.53 x 10-2; OR1.26 [0.98-1.62]). Conclusion: Our data confirm the association of PTPN2 gene variantswith susceptibility to both CD and UC in the German population. Given the association ofPTPN2 variants with other autoimmune diseases such as type 1 diabetes and Graves‘ disease,PTPN2 gene variants may partially explain the increased susceptibility of IBD patients forother autoimmune diseases.

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Response to Influenza Vaccine a/H1N1 2009 in Patients With InflammatoryBowel Disease on Anti TNF-Alpha TherapyGianluca Andrisani, Daniela Frasca, Alessandro Armuzzi, Alfredo Papa, Manuela Marzo,Carla Felice, Giammarco Mocci, Daniela Pugliese, Giovanna Vitale, Italo De Vitis, GianLudovico Rapaccini, Luisa Guidi

Aim: Patients with inflammatory bowel disease (IBD) are exposed to the same infectionsaffecting the community, in adjunct to the opportunistic infection related to the immunesuppression. Some of these infectious diseases may be prevented by the appropriate use ofa vaccination program. The immune response to vaccine in these patients is still unclear.Aim of the study was to assess the efficacy and safety of influenza A/H1N1 vaccine in patientswith IBD on anti TNF-alpha therapy. Materials and Methods: We enrolled 25 healthy controlsand 62 patients, 26 affected by Ulcerative Colitis (UC) and 36 by Crohn's disease (CD),all undergoing maintenance treatment with anti TNF-alpha. Patients were on anti TNFαmonotherapy (47) or on anti TNFα associated with immunosuppressor or corticosteroids(15). Mean age of patients was 45±16, of normal controls 38±14. All patients were vaccinatedwith the adjuvated vaccine A/ California/7/2009 (H1N1), Focetria®, Novartis. Sera wereobtained during the 2009/10 vaccination campaign before (T0) and 4-6 weeks after thevaccination (T1). Immune response to vaccination was measured by hemoagglutinationinhibition assay (HI). The results of HI are expressed as titers ≥1:40 at t1 (seroprotectionrate), as well as fold-increase after vaccination (titer at t1/titer at t0, seronversion rate),response rate (seroconversion or titer > 1:40 at T1 if lower at T0), geometric mean titer(GMT) and factor increase of GMT between T1 and T0. We recorded the activity indicesof disease before and after H1N1 vaccination. Results: IBD patients on anti TNF-alphaafter “pandemic” 2009 influenza vaccine obtained good HI seroprotection rates, while HIseroconversion rates and HI response rates were lower than HC (p<0.0001 by Fisher test).HI GMT and factor increase at T1 were significantly lower in IBD patients compared tohealthy controls (p<0.0001 and p=0.0026, respectively, by Mann Whitney test), and inpatients on combined therapy vs anti TNF-alpha monotherapy (p<0.022 and 0.034 respect-ively, by Mann Whitney test). Few patients in this study reported systemic adverse eventsafter the vaccination: 3% headache, 3% malaise and 2% shivering. None of them reporteda flare of the IBD. Activity indices showed no differences after vaccination. Conclusion: Inour patients the vaccine was safe and did not affect IBD activity. Moreover, patients withIBD undergoing anti TNF-alpha therapy showed a reduced response to the vaccine, ascompared to healthy controls, and among these patients those with anti TNF- α therapyand immunosuppressor were more impaired in the response to the vaccine but still able torespond. Vaccination is indicated to protect these patients. A double injection vaccinationschedule could be explored to improve the efficacy in the subgroup of patients on com-bined therapy.

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In Vivo and In Vitro Immune Response to Pandemic Influenza 2009 H1N1Vaccine in Inflammatory Bowel Disease Patients on Anti TNF-Alpha TreatmentGianluca Andrisani, Daniela Frasca, Alessandro Armuzzi, Alfredo Papa, Manuela Marzo,Carla Felice, Giammarco Mocci, Daniela Pugliese, Italo De Vitis, Gian LudovicoRapaccini, Luisa Guidi

Aim: Patients with inflammatory bowel disease (IBD) may be immunocompromised becauseof their treatment and for this reason, they might be considered as susceptible to and athigh- risk from complications of H1N1 virus infection. The immune response in thesepatients to vaccine is still unclear. Aim of this study was to assess the In Vivo and In Vitroresponse to the vaccine. Material and Methods: We enrolled 25 healthy controls and 16patients, 8 affected by Ulcerative Colitis (UC) and 8 by Crohn's disease (CD), all undergoingmaintenance treatment with anti TNF-alpha. Patients were on anti TNF-alpha monotherapy(n=10) or anti TNF-alpha associated with immunosuppressor or corticosteroids (combinedtherapy) (n=6). Mean age of patients was 46±15, of normal controls 38±14. All individualswere vaccinated with the monovalent vaccine A/ California/7/2009 (H1N1), Novartis. Bloodsamples were obtained during the 2009/10 vaccination campaign before (T0) and 4-6weeks (T1) after vaccination. Immune response to vaccination was measured In Vivo byhemoagglutination inhibition assay (HI) and ELISA. The results are expressed as fold-increaseafter vaccination (titer at T1/titer at T0). In Vitro, we evaluated the specific response of B cellsto the vaccine, as measured by AID (activation-induced cytidine deaminase) determination byqPCR. The results are expressed as fold-increase after vaccination. Results: Nine/10 (90%)of patients in monotherapy and 3/6 (50%) in combined therapy responded to vaccinationby HI, whereas 24/25 (96%) healthy controls responded (p=0.016 by Fisher test for combovs healthy controls). Six/10 (60%) patients in monotherapy also responded in H1N1-specificELISA for IgA and IgG, whereas 4/6 (66%) and 3/6 (50%) patients in combined therapyresponded in H1N1-specific ELISA for IgA or IgG, respectively. Six/10 (60%) patients inmonotherapy and 1/6 patients (17%) in combined therapy showed an In Vitro response asevaluated by AID by qPCR, as compared to 19/25 (76%) healthy controls ( p=0.013 byFisher test for combo vs healthy controls). The AID fold increase was significantly higherin the patients on monotherapy as compared with patients on combined treatment (p=0.0075 by Mann Whitney test). The fold increase AID and HI response were significantlycorrelated (p=0.001 by Spearman test, rho= 0.522). Conclusion: IBD patients showed reducedresponses to the vaccine both In Vivo and In Vitro as compared to healthy controls. AmongIBD patients, those in combined therapy showed the most significant reduction in the

S-274AGA Abstracts

response as compared to those undergoing monotherapy. We can propose the vaccinationto protect these immunocompromised patients.

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Infliximab Induces Regulatory Macrophages in Responders but Not in Non-RespondersAnne Christine W. Vos, Manon E. Wildenberg, Ingrid Arijs, Marjolijn Duijvestein, AukeVerhaar, Severine Vermeire, Gijs R. van den Brink, Paul J. Rutgeerts, Daniel W. Hommes

Introduction Regulatory macrophages play an important role in wound healing and guthomeostasis and have anti-inflammatory properties. We have previously shown that anti-TNF antibodies induce regulatory macrophages in an Fc region dependent manner In Vitro(Vos et al, Gastroenterology 2010). The aim was to examine the induction of regulatorymacrophages In Vivo, and to study a possible association between response and inductionof regulatory macrophages in patients treated with infliximab. Methods Colonic mucosalbiopsies were obtained during endoscopy from CD (n=6) and UC (n=4) patients before and4-6 weeks after first infliximab therapy. Response to infliximab was defined as endoscopicand histologic healing. Regulatory macrophages were defined as the proportion of CD206+(regulatory macrophagemarker) to CD68+macrophages (CD206+/CD68+) on immunohisto-chemistry. Results A significant (p = 0.0051) induction of regulatory macrophages wasobserved after treatment in responders to infliximab (n=5: 2 UC, 3 CD). Strikingly, thisinduction was absent in non-responders (n=5: 2UC, 3 CD). (Figure) The association betweenresponse and induction of regulatory macrophages was found in UC patients as well as inCD patients. Furthermore, non-responders had lower amounts of regulatory macrophagesat baseline (week 0), suggesting a defect in regulatory macrophage differentiation or recruit-ment in non-responders. Conclusion We show that infliximab induces regulatory macro-phages in responders but not in non-responders. This mechanism of action of infliximabmay play a role in mucosal healing in patients with IBD.

Sa1295

Short and Long Term Outcome of Infliximab Scheduled Therapy for Acute,Severe Ulcerative Colitis. A Prospective, Open Label, Single-Centre, Two-YearStudyKonstantinos Papamichael, Emmanuel J. Archavlis, Alexandros Smyrnidis, George Agalos,Nikolaos Kyriakos, Panagiotis Konstantopoulos, Dimitrios M. Tzivras, Ioannis Drougas,Dimitrios Tsironikos, Gerassimos J. Mantzaris

Introduction: The role of infliximab (IFX) as rescue therapy for acute severe UC (AS-UC)is still under investigation. The aim of our study was to assess the short and long termoutcome of IFX rescue therapy in patients with AS-UC. Patients and method: Prospective,open label, single-centre, two-year study. Eligible were patients with AS-UC (as defined bythe Truelove & Witts criteria plus an endoscopic Mayo score 3), aged 18-70 years, whowere failing a 5-day intensive steroid regimen (Sweden index > 8 on day 3) and fulfilledthe safety requirements for anti-TNF therapy. Patients received a single dose of IFX (5 mg/kg i.v.). Azathioprine (AZA) was continued in prior AZA users. Patients who did not improveor deteriorated proceeded to colectomy. Responders received additional induction doses (5mg/kg at weeks 2 and 6) and then scheduled IFX maintenance therapy (5 mg/kg q8 weeks).Steroids were gradually tapered off. Patients were followed in the outpatient clinic withmonthly visits for two years or to treatment discontinuation. At each visit, clinical assessmentand laboratory tests were performed. At two years, colonoscopy was performed and endos-copic lesions were graded using the Mayo index. The primary end-points were steroid-freeremission (SFR) and complete mucosal healing (CMH) at 2 years after initiation of IFX.Results: Between January 2007 and September 2010, 37 patients [20 males, median age 33(range 18-65) years] who fulfilled the entry criteria received IFX rescue therapy. Twentytwo patients had extensive and 15 had left-sided UC of median duration 3.5 (range 0.5-16) years. Six patients were smokers; 8 had extra-intestinal manifestations. Twelve patients(32.5%) proceeded to colectomy: 5 (13.5%) did not respond to the first infusion, one (2.7%)developed severe allergic reaction during the second infusion and 6 (16.2%) relapsed beforethe fourth infusion after a partial response to IFX induction regimen. Twenty five patients(67.5%) patients achieved SFR at 6 months. In 12/25 (48%) patients who received combina-tion therapy AZA was discontinued after 6 months. During subsequent follow up 5 initiallyresponders were withdrawn for severe flare of UC (n=1) or adverse events to IFX (pneumonia,refractory psoriasiform rash, high blood pressure, and pericarditis, respectively). Five patientsneeded dose escalation of IFX (10mg/kg) and/or shortening of the time interval betweeninfusions to regain response. At the end of the two years follow up, 20 patents (54%) werein SFR. Colonoscopy revealed CMH (Mayo score 0) in 12 patients and near CMH (Mayo score1) in 8 patients. Conclusion: In this study which mirrors real life experience, approximately 2/3 of patients who received rescue IFX for AS-UC avoided emergency colectomy and over50% were maintained in long-term SFR and achieved CMH or near CMH.

Sa1296

Serum Proteome Profile of Crohn's Disease Patients Treated With Infliximab:A Pilot StudyMaria Gazouli, Gerassimos J. Mantzaris, Konstantinos Papamichael, ΑggelikiPapadopoulou, Konstantinos Vougas, Nicholas P. Anagnou, George T. Tsangaris

Background: Infliximab (IFX) is an effective treatment for Crohn's disease (CD) but consider-able proportion of patients may fail to respond primarily or lose response over time. Despiteintensive research robust factors to predict the response to IFX of patients with differentCD phenotypes have not yet been identified. Considering the cost and adverse events oftreatment this is an important unmet demand. Proteomics arose with new techniques todiscover protein biomarkers which may be useful for diagnosis. Method: In a pilot study,we analyzed the serum proteome profile of CD patients with various responses to IFXinduction therapy (5mg/kg iv at weeks 0, 2, 6). In a cohort of 60 CD patients we selected18 patients (6 females; 36.92±12.45ys) who were classified as complete, partial, or primary