S198 Poster presentations

P470Infliximab treatment for paediatric Crohn’s disease:long-term outcomes at a single centre

P. Church1 *, J. Guan1, K. Frost1, A. Muise1, T. Walters1,A. Griffiths1. 1Hospital for Sick Children, Paediatrics, Toronto,Canada

Background: Infliximab (IFX) is effective in treating luminalCrohn’s disease (CD) in children (Hyams, 2007), but dataabout durability of response are limited. We reviewed theeffectiveness of IFX treatment in achieving short- and long-term clinical remission and normal linear growth in a single-center cohort.Methods: From 2000 to 2011 at SickKids, Toronto, 195children (63% male; median age 14.1 yrs, IQR 3.3) with luminalinflammatory CD (20% L1; 17% L2; 63% L3) received standard IFX3-dose induction. Median duration of diagnosed CD at initiationwas 19.9 mos (range 0.3 136.8). Responders continuedscheduled maintenance treatment +/ immunomodulator (IM).Records were retrospectively reviewed to extract at yearlyintervals: physician global assessment (PGA) of continuedresponse/remission vs. loss of response (LoR), PCDAI, lineargrowth, colonoscopic data and levels of IFX and antibodies(ATI). Durability of response was explored using survivalanalysis.Results: Rates of clinical response (judged by PGA) andremission (judged by PGA and PCDAI �10) were respectively,91% and 80%. Longer time from diagnosis to IFX inductionand being female were associated with a lower responserate. 20% of primary responders later stopped IFX (LoR: 56%;intolerance/complication: 30%). LoR rate was linear (6 to8%/year) over 5 years. Over the follow-up period, 52% requireddose escalation or interval shortening. In subjects with LoR,ATI were present in 88%. Concurrent IM use did not significantlyalter LoR, ATI or need for dose escalation. Data for growthare shown in the figure. Growth was significantly improved forthose who were Tanner 1 or 2 at induction. Being youngerat diagnosis and induction were significantly associated withimproved height. Follow-up endoscopy was performed in 26patients after IFX induction. Healing was observed in 50% (35%substantial, 15% complete).

Figure: Height improves significantly when growth potential remains atinduction.

Conclusions: These long-term data support the effectivenessof IFX in achieving durable response and improving growth inpatients with luminal Crohn’s disease.

P471Infliximab therapy in patients with chronic refractorypouchitis: efficacy and safety

A. Indriolo1 *, L. Campanati2, L. Ansaloni2, F. Caprioli3,E. Contessini Avesani4, P. Ravelli1. 1Ospedali Riuniti diBergamo, Gastroenterology and Digestive Endoscopy UnitII, Bergamo, Italy, 2Ospedali Riuniti di Bergamo, Surgery IUnit, Bergamo, Italy, 3University of Milan, Department ofGastroenterology, Milan, Italy, 4University of Milan, Division IIof General Surgery, Milan, Italy

Background: 25% of patients with inflammatory bowel disease(IBD) need surgery during the course of their life because ofrefractory intestinal disease at medical therapy or dysplasiae/o colorectal cancer. Restorative proctocolectomy withileal pouch-anal anastomosis (IPAA) has become the surgicalprocedure of choice in these patients. 23 46% of patients withIPAA develop chronic pouchitis not responding to antibiotics.Only a few studies evaluated the biological therapy in patientswith chronic refractory pouchitis.The aim of this study is analyze the clinical and endoscopicefficacy and related complications in patients with chronicrefractory pouchitis (CRP).Methods: A total of 431 patients with IBD were evaluated inour Center from January 2001 to October 2012. 14 patients(3.2%) underwent at restorative proctocolectomy with IPAA (10patients with Ulcerative Colitis, UC; 4 patients with Crohn’sDisease, CD). 4 patients have a definitive ileostomy. 6/10(60%) patients with IPAA (5 UC, and 1CD, 3 males, averageage: 42.1 years, range: 28 56) developed chronic refractorypouchitis and were been treated with infliximab (IFX) (5 mg/kg,0 2-6 weeks and every 8 weeks). The efficacy of IFX hadbeen evaluated with Pouchitis Disease Activity Index (PDAI).Endoscopic response evaluated before and after treatment.Mucosal healing mucosal healing had been defined as absence ofulcerations of mucosa. Complications during IFX therapy havebeen reported.Results: 6 patients treated with infliximab therapy (IFX) forCRP. Clinical and endoscopic remission, complications relatedwill be reported in the poster table. Significative difference formedian PDAI is present after IFX (p = 0.003). Mucosal healing ispresent in 50% of patients. Complications included only oneinfection in one patient: Herpes Genitalis.Conclusions: In our study 60% patients with IPAA developedchronic refractory pouchitis. Significative differences havebeen observed with PDAI before and after IFX therapy inpatients with chronic refractory pouchitis. Mucosal Healing waspresent in 50% of patients. We observed only one infection inone patient.However, additional largest studies are needed to evaluateanti-TNFalfa therapy in patients with chronic refractorypouchitis.

P472Infliximab therapy for inflammatory bowel disease inpatients post liver transplatation

A. Indriolo1 *, S. Fagiuoli2, L. Pasulo2, G. Fiorino3, S. Danese3,P. Ravelli1. 1Ospedali Riuniti di Bergamo, Gastroenterology andDigestive Endoscopy Unit II, Bergamo, Italy, 2Ospedali Riunitidi Bergamo, Gastroenterology I and Liver TransplantationUnit, Bergamo, Italy, 3IRCSS Umanitas, IBD Center,Gastroenterology, Rozzano, Italy

Background: From 54% to 90% of PSC patients develop IBD. 5%of patients with Ulcerative Colitis (UC) associated to PrimarySclerosing Cholangitis (PSC). To date, a few studies with a casereport or serial cases have been reported for the treatmentof refractory IBD following liver transplantation with anti-TNFalfa.

Clinical: Therapy and observation S199

The aim of this study is to evaluate the clinical and endoscopicefficacy, and safety of infliximab therapy for UC following livertransplantation in patients with PSC.Methods: We evaluated all patients clear diagnosis of UC whounderwent Orthotopic Liver Transplantation (OLT) at OspedaliRiuniti of Bergamo between January 2001 and September 2012and who had received inflixamab therapy for refractory IBDfollowing liver transplantation.Results: Four patients (all men; median age 39 years, range22 54 years) with UC (3) and pouchitis (1) who underwent OLTwere identified. Three patients (75%) experienced sustainedimprovement of IBD. Mucosal healing was observed in one ofthree patients (33%). Steroid treatment was interrupted duringinfiximab therapy in all patients. Adverse events included onlyone infection: molluscum contagiosum on face of one patient,treated with laser-therapy with resolution of symptoms. Nomalignancies were observed in all patients following infliximabtherapy. No hepatic reject was documented while on infliximabtherapy. One patient 25%) presented a recurrence of PSC twoyears before infliximab therapy (three years after OLT) and heunderwent a second OLT after 5 years after the first.Conclusions: Infliximab therapy appears to be effectivein patients with refractory ulcerative colitis after livertransplantation. Although no complications of hepatic graftfunction or reject were observed, additional largest studiesare need to evaluate the safety’s profile of biological therapycombined to anti-reject treatment in patients with refractoryIBD following liver transplantation.

P473Infliximab is more immunogenic and reaches lower troughlevels in ulcerative colitis patients compared to Crohn’sdisease patients

H. Bar-yoseph1 *, Y. Chowers1, S. Ben-Horin2, M. Waterman1.1Rambam, Gastroenterology, Haifa, Israel, 2Shiba,Gastroenterology, Tel Hashomer, Israel

Background: Infliximab is effective for treating Crohn’sdisease (CD) and ulcerative colitis (UC). However, it is unknownif serum drug levels (SDL) and Infliximab antibody (ATI)formation differs between CD and UC patients.Methods: SDL and ATI were prospectively determined in CDand UC patients on maintenance Infliximab therapy. Clinicaloutcomes were based on retrospective chart review. UC andCD patients (1:2 ratio) were matched for treatment (Infliximabdose & interval and percent of patients on combinationtherapy) and response. Mean SDL and ATI were compared usingChi-square test for categorical variables and Mann Whitney testfor continuous variables.Results: Thirty-six responding patients (12 UC, 24 CD) wereassessed. There was no difference between UC and CD groups ingender ratio, ethnicity, age at diagnosis, age at start of therapy,duration of therapy, disease duration prior to therapy, smokingstatus, treatment protocol and response to therapy. Mean ATIlevels were significantly higher in the UC group compared withthe CD group (10.34 and 1.48 mcg/ml, respectively, p = 0.029).ATI positivity (ATI >1 mcg/ml) was significantly more frequent inUC compared to CD (50% & 12.5%, respectively, p = 0.036). MeanSDL was 3.63 mcg/ml for UC and 4.32 mcg/ml for CD (p = 0.045)and 75% of UC patients had SDL �1 mcg/ml compared to 37.5%of CD patients (p = 0.038).Conclusions: UC patients on maintenance infliximab therapydevelop more ATI compared with CD patients. Serum infliximablevels associated with response to Infliximab maintenance areslightly lower in UC compared to CD. Larger cohorts arerequired to support these observations.

P474Infliximab induction therapy on AA amyloidosis associatedwith Crohn’s disease: case report

A. Pukitis1 *, E. Ostrovskis1, T. Zake2, J. Pokrotnieks2. 1PaulsStradins Clinical University Hospital, Gastroenterology Center,Riga, Latvia, 2Riga Stradins University, Riga, Latvia

Background: Secondary systemic (AA) amyloidosis is a rare butserious complication of Crohn’s disease (CD) with high mortalityrate. Infliximab (IFX) is proven to induce clinical responseand remission in CD. Unfortunately, only a few case reportshave shown the therapeutic effects of IFX on CD-associatedamyloidosis.Methods: We report a case of a patient with CD complicatedby AA amyloidosis, nephrotic syndrome, chronic kidney disease(CKD) and treated with IFX as induction therapy.Results: Patient is a 24-year-old man diagnosed withCD terminal ileitis at the age of 18 years. Thereafter,patient was treated with 5-aminosalicylate and azathioprineand maintained in clinical remission. Six years later hewas admitted due to marked peripheral edema due tohypoalbuminemia, ascites, diarrhea and severe malnutrition.Laboratory tests showed nephrotic syndrome and renal biopsywas performed to confirm a diagnosis of AA amyloidosis. Serumamyloid A protein level was increased to 1082 mg/l (normalvalue (NV) <6.4 mg/l), C-reactive protein (CRP) to 13.0 mg/l(NV <5.0 mg/l), laboratory findings showed proteinuria 18.0g/day, serum creatinine level 0.88 mg/dL and normal estimatedglomerular filtration rate (eGFR) 113 ml/min/1.73m2. Thepatient received treatment with corticosteroids, azathioprine(2.5 mg/kg), enteral and parenteral nutrition to achieveremission of CD and additionally induction treatment with IFXwas started to reduce the complications of AA. The levelof eGFR (72 ml/min/1.73m2) revealed stage 2 CKD beforetreatment with IFX. Patient received IFX (5 mg/kg body weight)in three infusions at 0, 2, 6 weeks. There were no adverseeffects from the medication. After the IFX induction therapy:serum amyloid A protein level was decreased to 22.5 mg/l(for 97.9%) and CRP to 3.9 mg/l, with improvement of bowelsymptoms. There had been no notable changes in proteinuria,but significantly increased the reduction of renal function.Laboratory tests showed a progressive increase in serumcreatinine level to 3.69 mg/dL and decreased eGFR to 4 stageof CKD.Conclusions: In this rare CD combined with systemic AA casesignificant decrease of amyloid A protein level was achieved bythe IFX induction treatment. An expected stabilization of renalfunction after IFX induction therapy was not achieved due toirreversible systemic amyloidosis damage. Theoretically longerterm IFX treatment may delay the progression of amyloidosisand prevent further progression of the renal failure.

P475Infliximab concentration is associated with mucosal healingin intestinal bowel disease (IBD)

S. Paul1, E. Del Tedesco1, H. Marotte1, M. Rinaudo-Gaujous1,J.M. Phelip1, L. Peyrin-Biroulet2, X. Roblin1 *. 1University ofSaint Etienne, France, 2Nancy, France

Background: For the first time, relationship between infliximabconcentration and mucosal healing (HM) is evaluated in IBD,after therapeutic optimisation.Methods: We included, in a prospective study, all IBD subjectsin infliximab (IFX) failure at 5 mg/kg, after a primary response.A clinical relapse was defined by a CDAI >220, a faecalcalprotectin >400 mg/g and a C reactive protein >10 mg/l inCD. In UC, clinical relapse was considered when the Mayo scorewas >7 with a Mayo endoscopic subscore >1. An increment ofthe dose to 10 mg/kg IFX was managed in all patients. IFXconcentration and ATI were evaluated from serum samples