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sthe others. Predictive factors for CPM and RPM were assessed in a multivariate analysis.Results: One-hundred-twenty-one patients (69 W; median age: 27.4 years) have beenrecruited during the study period. Nine (7%), including 7 women, have developped a CPM(8 cases of psoriasis), and 10 (8%), including 7 women, a RPM (all with severe and disablingpolyarthralgia). Median ITL were 5.87 (range: 0.52-19.53) μg/mL in patients with CPM and5.12 (0.00-49.12) μg/mL in those without (P=0.560), and 1.9 (0.00-13.5) μg/mL in patientswith RPM and 5.57 (0.00-49.12) μg/mL in those without (P=0.058). ATI have been detectedin 16 (13%) patients, including 3 with RPM (P=0.128) and none with CPM (P=0.605). Inmultivariate analysis, no predictive factor associated with CPM could be identified and, thesole factor associated with RPM was anti-nuclear antibodies > 1/100 at inclusion. Conclusion:ITL and ATI levels were similar in patients developing IFX paradoxical manifestations. Assuggested by elevated antinuclear antibodies, RPM could be related to an autoimmunedisorder induced by IFX.

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Bilberry Ingestion Improves Disease Activity in Mild to Moderate UlcerativeColitis - an Open Pilot StudyLuc Biedermann, Jessica Mwinyi, Michael Scharl, Pascal Frei, Jonas Zeitz, Gerd A. Kullak-Ublick, Stephan R. Vavricka, Gerhard E. Krammer, Michael Fried, Achim Weber, Hans-Ulrich Humpf, Simone Peschke, Alexander Jetter, Gerhard Rogler

Background A significant fraction of patients with ulcerative colitis (UC) is not sufficientlycontrolled with conventional anti-inflammatory or immunosuppressive therapy or suffersfrom therapy related side effects. Interest in the therapeutic potential of polyphenols hasrisen in recent years for several diseases, including coronary heart disease or colorectalcancer. Anthocyanines, highly abundant in bilberries (Vaccinium myrtillus), were shown tohave antioxidative and antiinflammatory effects. We therefore investigated the therapeuticpotential of a peroral bilberry preparation in mild to moderate active UC. Methods In an openpilot trial with a total follow-up of 9 weeks the effect of a daily standardized anthocyanine-richbilberry preparation, equaling an intake of around 300g (10.6 oz) of fresh bilberries perday, was tested in 13 patients with mild to moderate UC (CAI 4-8). Clinical, biochemical,endoscopic and histologic parameters were assessed. Results At the end of the treatmentinterval (6 weeks) 63.4% of patients achieved remission (CAI <4), the primary endpoint,while 90.9% of patients showed a response (drop of CAI ≥3 points). In all patients adecrease in total Mayo Score was detected. A significant sustained beneficial effect (46.2%and 72.7% for remission and response, respectively) was found at the end of the follow upperiod. Fecal calprotectin levels significantly decreased during the treatment phase (baseline:mean 778ug/g, range 192-1790ug/g; end of treatment: mean 373ug/g, range <30-3027ug/g), including 4 patients achieving undetectable levels at end of treatment. However, anincrease was observed after cessation of bilberry intake. In addition, a decrease in endoscop-ically (endoscopic Mayo Score) and histologically (Riley) indices confirmed the beneficialeffects of the bilberry preparation. Adherence to bilberry intake during the entire treatmentperiod and patient satisfaction were high. No serious adverse events were observed. Conclu-sion This is the first report on the promising therapeutic potential of a standardized anthocy-anine-rich bilberry preparation in UC in humans. The results, although limited by the smallpatient number and the open study design, clearly indicate a therapeutic potential of bilberriesin UC. Further studies on mechanisms and randomized clinical trials are warranted.Patient characteristics

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ITT, intention to treat population; PP, per protocol; UC, ulcerative colitis; 5-ASA, 5 aminosal-icylates

Figure 1. Fecal calprotectin before, during and after bilberry intake. Boxplots depictingmedian (solid black line across the box), interquartile (IQ) range (box represents the middle50% of Calprotectin values) and values within 1.5 times the IQ range (indicated by whiskers).An outliner (cases with values between 1.5 and 3 times IQ range, small circle, 1), and anextreme (value more than 3 times the IQ range, asterisk, 2) value at week 7 are depicted separ-ately.

Sa1887

Adalimumab in Active Ulcerative Colitis: A “Real-Life” Observational StudyAlessandro Armuzzi, Livia Biancone, Marco Daperno, Alessandra Coli, Vito Annese,Sandro Ardizzone, Paola Balestrieri, Fabrizio Bossa, Fabiana Castiglione, Michele Cicala,Silvio Danese, Renata D'Incà, Pietro Dulbecco, Giuseppe Feliciangeli, Walter Fries,Stefania Genise, Paolo Gionchetti, Stefano Gozzi, Anna Kohn, Roberto Lorenzetti, MonicaMilla, Sara Onali, Claudio Papi, Luigi Giovanni Papparella, Daniela Pugliese, Sara Renna,Chiara Ricci, Fernando Rizzello, Raffaello Sostegni, Luisa Guidi, Ambrogio Orlando

Background and aim: The effectiveness of adalimumab (ADA) in the treatment of ulcerativecolitis (UC) is under debate. Controlled trials have shown that ADA is significantly betterthan placebo for both induction and maintenance of remission, but the absolute benefit issmall. We report data on the effectiveness of ADA in a large cohort of patients with activeUC. Methods: Patients with active UC treated with ADA in 21 Italian referral centres havebeen collected. Clinical characteristics before and after ADA treatment were reported in acommon database. Active UC was defined as a partial Mayo score≥2. All patients receivedADA induction and maintenance regimen and concomitant medications according to clinicaljudgement. Co-primary endpoints were clinical remission (partial Mayo score≤1) at 4, 12,

24 and 54 weeks. Secondary endpoints were sustained clinical remission, steroid discontinu-ation, endoscopic remission and need of colectomy. Results: Eighty-two patients (30 male;median age 39 years, IQR 32-48) have been enrolled. Main indications for ADA treatmentwere steroid-dependency (45%), steroid-resistance (23%) and extraintestinal manifestations(15%). Most of patients (78%) received previous infliximab treatment. Median partial Mayoscore at baseline was 6 (IQR 4-7). ADA induction regimen was 160/80 mg (88%) or 80/40mg (12%) and maintenance treatment was 40 mg every other week for a median time of11 months (IQR 4-17). During follow up 30% of patients required dose-escalation. Clinicalremission at 4, 12, 24 and 54 weeks was achieved in 13/82 (16%), 20/78 (27%), 26/75(35%) and 24/60 (42%) patients, respectively. Sustained clinical remission at 12, 24 and54 weeks was achieved in 10/60 (17%) patients. Thirty-three of 55 patients (60%) receivingcorticosteroids at baseline were able to discontinue them. Forty-seven patients underwentbaseline and follow-up endoscopy after a median of 11 months (IQR 3-13). Endoscopicremission was achieved in 21/47 patients (45%). During the study period, 18 patients (22%)underwent colectomy after a median of 5.5 months (IQR 2-14). No significant differencesin remission rates at 4, 12, 24 and 54 weeks and colectomy rates were observed betweenanti-TNF alpha naïve and non-naïve patients. Conclusions: In this large “real-life” experienceADA appeared to be effective in active UC. One fourth of patients achieved clinical remissionwithin three months. In patients receiving scheduled maintenance treatment for one year theremission rate was about 40%. Although ADA shows a steroid-sparing effect, the probability ofcolectomy for treatment failure is high.

Sa1888

Need for Infliximab Dose Intensification in Patients With Crohns Disease andUlcerative ColitisCarlos Taxonera, Juan L. Mendoza, David Olivares, María M. Cañas, Fermin EstremeraArevalo, Manuel Diaz-Rubio

Background: A relatively high efficacy of infliximab dose intensification has been reportedin patients with Crohns disease (CD) who have lost response to the drug. Approximately15% CD patients-year on infliximab needed infliximab dose intensification. Data on theefficacy of infliximab dose intensification in patients with ulcerative colitis (UC) are lacking.Requirement for infliximab dose intensification in UC are also not well known. The aim ofthe study was to compare the need for and timing of infliximab dose escalation in twocohorts of patients with CD or UC. Methods: In this single-center study, dose intensificationwas determined by two senior staff specialized in IBD. We compared the rates of patientsand of patients-months on infliximab who needed infliximab dose intensification (either byincreasing the dose to 10 mg/kg or by shortening the dosing interval) in the cohorts of CDor UC patients. We also compared the interval between infliximab first induction dose andthe first escalated infliximab dose. Intensification-free survival was estimated by the Kaplan-Meier method. Results: We evaluated 61 patients with CD (mean age 42 years; 54% female)and 41 patients with UC (mean age 44 years; 41% female). Three in four CD patients vs83% UC patients (p=0.38) were receiving an immunomodulator when infliximab is initiated.After a median follow-up of 12.5 months (IQR, 7-23 months) and 8.5 months (IQR, 5-13months) for CD or UC patients, respectively, 16/61 (26 %) of CD patients required infliximabintensification vs 16/41 (39%) of UCpatients (p=0.16). The rate of patient-monthwho neededinfliximab dose intensification was 1.5% vs 3.9% (p<0.001) for CD and UC, respectively. Inpatients who underwent infliximab optimization, median time between the first infliximabinduction dose and the first escalated dose was 10.5 (IQR, 8.7-15.2) months vs 6.2 (IQR,3.5-8.3) months (p=0.02) for CD and UC, respectively. Survival curves showed that patientswith UC had an increased probability of needing infliximab dose intensification whencompared with CD patients (p=0.02). Conclusions: The rate of patient-month who neededinfliximab dose intensification is higher in UC patients when compared with CD patients.Patients with UC required intensification of infliximab dosing earlier and infliximab intensi-fication-free survival was also lower in these patients.

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10 Year Performance of Anti TNF Biologic Therapy in Inflammatory BowelDiseaseLilani P. Perera, Yelena Zadvornova, David G. Binion, Corinne Guilday, Daniel J. Stein,Amar S. Naik, Nanda Venu, Kari Best, Susan Skaros

Durability of individual anti-TNF therapy agents in moderate to severe inflammatory boweldisease [IBD, Crohn's disease (CD) and ulcerative colitis (UC)] is limited and many patientswho initially respond to biologics will discontinue therapy due to loss of response orintolerance or major complications. Data on performance and safety of long term anti-TNFtherapy with individual or multiple agents is lacking. The aim of this study was to describelong term outcomes of patients who have been on one or more anti TNF agents for over10 yrs. Method: A retrospective cohort study at a single tertiary referral center. Demographicdata, diagnosis, duration of disease at time of first biologic, disease type (inflammatory - i,structuring- s and penetrating- p), disease extent (small bowel- sb, large bowel- lb, smallbowel/ large bowel- sb_lb and pan GI- pan), exposure to immunomodulators, Short Inflam-matory Bowel Disease Questionnaire (SIBDQ) score, disease activity for CD ,Harvey-Bradshawindex (HB) and UC activity index for UC , CRP, ESR surgeries, hospitalizations andClostridiumdifficile infection and smoking status as well as side effects and major complications werereviewed. Results: Out of 929 patients who received anti-TNF therapy, there were 27 whoreceived treatment for > 10 years (2.9%). 17 of them had been on a single agent (IFX),while 5 had been on 2 agents and 5 were on their 3rd anti TNF. Neoplastic complicationsoccurred in 11% of patients (1 testicular cancer, 1 anal cancer and 1 non-melanoma skincancer). All patients responded to appropriate treatment and continued on anti TNF therapywithout recurrence. Significant infections occurred in 22% of patients (2 with recurrentURIs, 2 with recurrent skin abscesses and 2 with pyelonephritis). Conclusions: Anti-TNFtherapy can be safely continued for greater than 10 years in a small subset of IBD patients.Malignancies and infectious complications were significant but did not lead to anti TNFdiscontinuation. Larger studies are needed to define long term safety and efficacy of antiTNF therapy in IBD.

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Sa1890

White Cell Apheresis (WCA) With Adacolumn is Effective in Selected Casesof Chronic Refractory Colitis With High Histological ActivityPrem Premchand, Charlotte Ford, Dinesh Venkama

Treatment options for patients with chronic refractory colitis are limited. Recent anti-TNFtrial data has been disappointing demonstrating only modest benefit in achieving clinicalremission, suggesting a need to consider alternative therapeutic options. White cell apheresis(WCA) is effective in inducing clinical remission in chronic refractory colitis in patientswith a strong inflammatory burden at baseline and histologically active disease. Previousmultinational sham controlled trials have demonstrated significant improvement whenpatients with high histological activity (modified Rileys score) are selected for treatment. Aprospective study was conducted in 30 patients with severe steroid -dependent or steroid-refractory ulcerative colitis referred for WCA. Inclusion criteria were (i) High disease activityscore (partial Mayo score ≥ 6) (ii) Intractable symptoms despite treatment with steroidsand/or immunosuppressants (iii) Severe disease at endoscopy and histologically. The aimwas to induce clinical and IBD-Q remission at 12 weeks. A Mayo score ≤ 3 defined clinicalremission. The 32 item Inflammatory Bowel Disease questionnaire (IBD-Q) was used toassess quality of life prior to treatment and at 12 weeks, response was defined as an increasein IBD-Q total score of >16 points, remission a score of ≥ 170 points. Results PatientCharacteristics; Prior to treatment 28 patients (93.3%) were prescribed 5-ASA compounds.12 patients (40%) were prescribed topical therapies (5-ASA enemas or suppositories /steroidsenemas). 27 patients (90%) were steroid dependent (Prednisolone mean dose 21.1mg,median 20mg). 3 patients (10%) were steroid refractory (no response to high dose oralsteroids). 13 patients (43.3%) were prescribed Azathioprine of the remainder all had docu-mented intolerance or a contraindication. 1 patient (3.3%) was prescribed 6 Mercaptopurine.5 patients had failed Infliximab (16.6%) and in 1 patient (3.3%) it was contraindicated. 1patient (3.3%) had failed intramuscular Methotrexate. Outcomes At week 12 clinical remis-sion (Mayo score ≤ 3) was achieved in 22 patients (73.3%), 18 patients (60%) were nolonger prescribed oral steroids. IBD-Q remission at week 12 was achieved in 19 patients(63.3%). Of the remainder, 5 patients (16.6%) achieved an IBD-Q response. Of 8 patients(26.6%) who failed to achieve clinical remission at 12 weeks, 1 achieved delayed remissionat 20 weeks. Of the remaining 7 treatment failures, 5 underwent colectomy (16.6%).Conclusions. WCA can be effective in inducing clinical remission and improving quality oflife (IBD-Q) indices in chronic severe steroid refractory ulcerative colitis with highly activedisease histologically. This data series suggests WCA should be considered before colectomyin this challenging patient group.

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