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sresponse to long term IFX treatment in CD. Methods: CD patients treated with IFX wereretrospectively classified as having: A) Maintained response: Good initial and maintainedclinical response (n=48). B) Secondary non-response: Good initial clinical response followedby loss of response (n=24). C) Primary non-response: Inadequate clinical response to theinitial three IFX infusions (n=15). S-IFX- and ADA levels were measured by RIA. Results:IFX trough levels were significantly higher, and ADA significantly lower, in patients withmaintained clinical response (median s-IFX 2.4 μg/ml, median ADA 0 U/ml) compared topatients with secondary loss of response (median s-IFX 0 μg/ml, median ADA 34 U/ml)(p<0.0001). In primary non-responders, ADA levels were below detection limit and s-IFXwas higher than in the two other groups. Receiver Operating Characteristic (ROC) analysisshowed that IFX trough levels ≦0.5 μg/ml were associated with loss of response with asensitivity of 81% (95% confidence interval 58-95%), and a specificity of 80% (65-91%),while ADA levels ≧10 U/ml were associated with loss of response with a sensitivity of 75%(53-90%), and a specificity of 85% (72-94%). Combined assessment of ADA- and s-IFXtrough levels using the above mentioned cut-off levels had a sensitivity of 79% (54-93%),and a specificity of 89% (72-96%) (combined test regarded as positive if both tests werepositive and considered negative if both tests were negative). Conclusion: ADA levels ≧10U/ml and s-IFX ≦0.5 μg/ml measured by RIA had a sensitivity and specificity of 79% and89% for discrimination between various clinical response types in patients with Crohn'sdisease treated with infliximab. Monitoring of anti-drug-antibody levels and s-infliximabtrough levels in infliximab-treated patients may improve the clinical decision making ininfliximab therapy. 1 Ainsworth MA et al. Am J Gastroenterol 2008; 103:944-8.

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Anti-TNF Therapy in Elderly People in IBD: An Italian Multicentre SurveyMario Cottone, Anna Kohn, Marco Daperno, Alessandro Armuzzi, Luisa Guidi, RenataD'Incà, Fabrizio Bossa, Livia Biancone, Paolo Gionchetti, Sandro Ardizzone, Claudio Papi,Walter Fries, Silvio Danese, Maria Cappello, Fabiana Castiglione, Ambrogio Orlando

Background: Many trials on anti-TNF therapy in adults IBD regard people from 18 to 65years. Few data are available on the role of biologics in people over 65 years. Aim of thestudy : to evaluate the risk and benefits of anti TNF therapy in an Italian series of IBDpatients over 65 looking to remission rate , side effects and mortality. Patients and Methods:from 2000 to 2009 in 14 tertiary centers 2405 pts with IBD were treated with Infliiximaband 601 with Adalimumab . Among them data on patients over 65 years age treated withthe 2 biologics were collected . Every center collected prospectively the data on biologictreatment on an excel data base . 81 patients (2.4% of the total patients treated with biologics). 38men/43 women;37Ulcerative Colitis/44 Crohn's disease were treated (68with Infliximaband 13 with Adalimumab ). The mean follow-up from first biological treatment was 26months .The primary end point was remission ,side effects and survival. Results: In CD theoverall rate of remission was 65 % and in UC the overall remission rate was 61 % . 8(10%)severe infections was observed . 2 neoplasms (rectal cancer and prostatic tumor)wereobserved during the follow-up . 9 deaths (11%) were observed ; 6 during treatment (4 dueto severe infections and two to DIC postcolectomy and 3 after at least 3 months from thelast treatment (one due to rectal tumor and two to cardiovascular disease) . Maintenancetreatment was carried out in 43 patients (53%). Conclusions: an high rate of severe infectionand mortality was observed in this series of elderly people with IBD treated with anti/TNFtherapy. The role of anti/TNF on mortality is to be elucidated considering that older patientswith IBD related hospitalizations have higher mortality than younger patients (1). Furtherprospective data on the elderly population are warranted. (1)Ananthakrishan A,Mc GinleyE, Binion D. Inflammatory bowel disease in the elderly is associated with worse outcomes:anational study of hospitalizations.Inflamm Bowel Dis 2009;15;182-

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Predictive Factors of Response to Infliximab in Inflammatory Bowel DiseasesAnne Bourrier, Philippe Seksik, Harry Sokol, Catherine Johanet, Isabelle Nion-Larmurier,Laurent Beaugerie, Jacques Cosnes

Introduction: Infliximab (IFX) is indicated in the inflammatory bowel disease (IBD) refractoryto first line immunomodulators (IM). Rates of response after induction (about 65% at 8weeks) and in maintenance (50% at 2 years) are similar in both Crohn's disease (CD) andulcerative colitis (UC). Identification of predictive factors of response to IFX is required asearly use of IFX is more and more proposed while loss of response can occur. The aim ofthis study was to search for predictive factors of response to IFX in a cohort of referred IBDpatients irrespective of disease phenotype (CD or UC). Patients and Methods: Among patientswith IBD followed in a tertiary centre, who received at least one infusion of IFX for luminaldisease between 1999 and 2008, 182 patients (median age 29 years, 44 % men, 73% CD)constituted the cohort. Response to IFX induction was assessed clinically and maintenanceof response was defined by IFX continuation over time. Predictive factors of response toIFX at induction were searched by univariate and multivariate analysis testing the followingvariables: age, sex, IBD phenotype, family history of IBD, Montreal classification, smokingstatus, extra-intestinal manifestations, ASCA and/or pANCA serology, concomitant IM at thefirst infusion of IFX. The same variables entered the analysis of predictive factors of mainten-ance of response using log rank and Cox model. Results: 141 (77.5%) patients were respond-ers to IFX induction, and 116 of them continued with IFX maintenance regimen. At 2 years,78 patients were responders to IFX (42.9% from the initial cohort). The only predictivefactor of response to IFX induction treatment was concomitant treatment with IM (84%responders vs 48% of nonresponders, p <0.001). The 2 predictive factors of response toIFX maintenance therapy were: concomitant treatment with IM (OR=0.47, IC95 [0.23-0.95])and small bowel involvement (CD with the small bowel and UC with pouchitis) (OR=1.96,IC95 [1.02-3.78]). The IBD phenotype, pANCA, ASCA, smoking status and other variablesstudied did not affect the response to IFX. Conclusion: Our results confirm the positiveimpact of combination IM regimen both for induction and maintenance responses to IFXin IBD patients. Involvement of the small bowel jeopardizes the maintenance response to IFX.

S-688AGA Abstracts

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Thiopurine-Induced Myelotoxicity in Inflammatory Bowel Disease (IBD): AMulticenter StudyMaria Chaparro, Paula Vázquez de Parga, Manuel Van Domselaar, Raquel García, AliciaAlgaba, Pilar Martínez, Isabel Vera, Ignacio Marin-Jimenez, Angel Ponferrada Diaz, CarlosTaxonera, Antonio López-San Román, Pilar Lopez-Serrano, Fernando Bermejo, BegoñaCasis, Yago Gonzalez-Lama, Amelia Rodriguez Nogueiras, José Maté, Javier P. Gisbert

Background: Thiopurine drugs azathioprine and mercaptopurine have shown to be effectivein the treatment of patients with IBD. Although these drugs are well tolerated by mostpatients, many physicians are reluctant to use them because their associated adverse events(AE). Myelotoxicity is the most potentially lethal AE in patients on thiopurine therapy.Aims: To evaluate the incidence, clinical characteristics and possible predictive factors forthiopurine-induced myelotoxicity in patients with IBD. Methods: Retrospective review ofall cases of myelotoxicity caused by thiopurine drugs in a multicentric cohort of patientsdiagnosed with IBD. Myelotoxicity was defined as a blood count of leucocytes lower than3,000/ml, neutrophils lower than 1,500/ml or platelets lower than 100,000/ml. Long-termincidence of myelotoxicity was estimated using the Kaplan-Meier analysis. Cox-regressionanalysis was performed to identify potential predictive factors of myelotoxicity. Results: 90patients with myelotoxicity (mean age 40 years, 57% female) were reported among 750patients treated with thiopurines. 38% had ulcerative colitis and 62% Crohn's disease. 64%were on azathioprine and 36%onmercaptopurine. The cumulative incidence of myelotoxicitywas 12%. The risk of myelotoxicity was higher with mercaptopurine than with azathioprine(OR=8; 95% CI=3-24). Myelotoxicity due to thiopurines was reported a median of 6 monthafter starting treatment (range 0.5-148 months). Leucopenia occurred in 73%, neutropeniain 70%, thrombocytopenia in 9% and anaemia in 54% of patients. 88% of patients wereasymptomatic at the onset of the myelotoxicity, 9% developed fever, and 3.3% infections.Twelve patients (13%) were hospitalized due to myelotoxicity (median length of hospitaliza-tion, 15 days). Five patients (5.6%) received blood transfusion. Thiopurine treatment wasdiscontinued in 39 (43%) patients, dosage was reduced in 41 (46%) and was kept unchangedwith close follow-up in 10 (11%). Myelotoxicity had a favourable outcome in all cases, withnormalization of the blood count in a median of 15 days (range 0.5-12 months). Thiopurinetherapy was re-started with the initial dosage in 20 patients and only 1 of them (5%)developed leucopenia again. Conclusions: 1. More than 10% of patients treated with thiopur-ines developed myelotoxicity during follow-up. 2. The majority of patients were asymptom-atic, but approximately 10% were hospitalized due to myelotoxicity. 3. The time to theonset of the myelotoxicity varied widely from few days to more than 12 years. 4. Mercaptopur-ine was associated with a higher risk of myelotoxicity than azathioprine.

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Efficacy and Safety of Infliximab Rescue Therapy After Cyclosporine Failurein Patients With Steroid-Refractory Ulcerative Colitis: A Multicenter StudyMaria Chaparro, Paula Burgueno, Eva Iglesias Flores, Julian Panes, Fernando Muñoz,Pilar Nos, Juan Luis Mendoza, Carlos Jimenez, Luisa Castro, Xavier Calvet, ManuelBarreiro, Silvia Gomez Senent, Montserrat Andreu, Miriam Manosa, Maria Gomez-Garcia,Fernando Gomollon, Joaquín Hinojosa, Olga Pérez Nyssen, Javier P. Gisbert

Background:Cyclosporine (CyA) has shown to be effective in patients with steroid-refractoryulcerative colitis (UC).In patients who fail to this drug, a third-line therapy with infliximab(IFX) can be considered to avoid colectomy.It is unknown the efficacy and safety of thissequential treatment. Aim:To assess the efficacy and safety profile of IFX treatment afterCyA failure in patients with a steroid-refractory flare of UC. Methods:Retrospective reviewof medical records of patients with a steroid-refractory flare of UC who did not respond toCyA and received a rescue therapy with IFX within a month. The severity of the flareand response to the treatment was estimated based on the Lichtiger index.The cumulativeprobability of colectomy was calculated using the Kaplan-Meier analysis.Cox-regressionanalysis was performed to identify potential predictors of colectomy. To evaluate the safetyprofile of this treatment strategy, any adverse event which occurred from the first infusionof IFX was considered. Results:Fifty-one patients (mean age 46 years,61% male) with steroid-refractory UC treated with IFX after CyA failure were included.Seventy percent had pancolitis,and 31% were on azathioprine. The mean number of flares suffered by these patients was2, and they had received a mean of 1 cycle of steroids.Median baseline Lichtiger index was13. Seventy-eight percent of patients received intravenous and 22% oral CyA. The mediantime from the last CyA to the first IFX infusion was 12 days. After the first IFX infusion,11% of patients reached remission, and 77% partial response. From the 39 patients thatreceived the third IFX infusion, 60% achieved remission, and 31% partial response. Fifteenpatients (29%) came to colectomy within a median of 5 weeks. In the multivariate analysis,the initial treatment with oral (instead of intravenous) CyA was associated with higher riskof colectomy (OR=3.7,95%CI=1.2-11). The rate of adverse events was 25% (6 infections,3 infusional reactions, 1 leukopenia, 1 bowel perforation, 1 fever and 1 peripherical neuro-pathy). One death occurred in a 40 year-old man who failed CyA and IFX and underwentsurgery 10 days after the first IFX infusion; he died due to pneumonia. Conclusions:Treatmentwith IFX avoids colectomy in 2/3 of UC patients who failed CyA. However, due to the rateof adverse events and even mortality, the decision of administering sequential therapy (CyA-IFX) should be individualized.