P179 INTENSIFICATION OF INFLIXIMAB (IFX) THERAPY IN CROHN'S DISEASE: EFFICACY AND SAFETY

P179 INTENSIFICATION OF INFLIXIMAB (IFX) THERAPY IN CROHN'S DISEASE: EFFICACY AND SAFETY

58 fied into adverse events, clinical refractoriness (at least 3 months therapy), or non-compliance. Therapeutic effectiveness was assessed by calcula...

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58 fied into adverse events, clinical refractoriness (at least 3 months therapy), or non-compliance. Therapeutic effectiveness was assessed by calculating those patients continuing thiopurines and were considered to be in remission, based on clinical, laboratory and endoscopic findings. Results: At the academic hospital, 281/781 IBD patients were included (63% female). Median age at start of thiopurine therapy was 34 years (range 1171). Crohn' s disease (CD) and ulcerative colitis (UC) were diagnosed in 67% and 33%, respectively. Thiopurines were continued in 117/281 patients, of which 78% remained in remission after two years. Fifty-eight percent discontinued thiopurines after a median duration of 6 months (range 0-174) due to adverse events (69%), refractoriness (24%), remission (5%) and noncompliance (2%). At the general district hospital, 72/416 IBD patients were included (47% female). Median age at initiation of thiopurines was 39.5 years (range 17-84). CD and UC were diagnosed in respectively 47 and 53 percent. Forty percent continued thiopurines, of which 83% remained in remission after two years of therapy. 43/72 discontinued therapy after a median duration of 2 months (range 0-95), due to adverse events (63%), refractoriness (19%), remission (16%) and non-compliance (2%). Significant differences between the both cohorts were an absolute number of thiopurine users (36% versus 17%), sex (P=0.015, Mann-Whitney), age (P=0.010, Mann-Whitney) and distribution of UC (P=0.000, Mann-Whitney). Conclusion: Analysis of two 8-years interception cohorts of an academic and general district hospital demonstrated that the therapeutic effectiveness of thiopurines in IBD patients was 40%. Sixty percent discontinued thiopurines, mostly due to adverse events. Significant differences between the cohorts were the number of thiopurine users, sex, age and distribution of UC.

P179 INTENSIFICATION OF INFLIXIMAB (IFX) THERAPY IN CROHN' S DISEASE: EFFICACY AND SAFETY M. Chaparro 1 , P. Martínez-Montiel 2, M. Van Domselaar 3 , F. Bermejo 4 , J. Pérez-Calle 5 , B. Casis 2 , A. López-San Román 3 , A. Algaba 4 , J. Maté 1 , J.P. Gisbert 1 . 1 La Princesa Hospital, Madrid, Spain; 2 12 de Octubre Hospital, Madrid, Spain; 3 Ramón y Cajal Hospital, Madrid, Spain; 4 Fuenlabrada Hospital, Madrid, Spain; 5 Alcorcón Hospital, Madrid, Spain Introduction: The response of Crohn' s disease to IFX therapy is initially high. However, a loss of efficacy is observed in some cases over time. In such patients with loss of response, an IFX therapy “intensification” has been recommended. Nevertheless, it is still unknown whether the beneficial effect of this intensification is prolonged or just transient. Aims: 1) To study the short- and long-term response of Crohn' s disease patients treated with IFX intensification (e.g., higher doses or shortened intervals). 2) To evaluate the adverse effects associated to therapy intensification. Methods: Retrospective multicenter survey. We included Crohn' s disease patients who had been treated with at least the three induction doses of the standard IFX therapy (5 mg/kg 0-2-6 w), and who later on needed treatment intensification (10 mg/kg/8w or 5 mg/kg/4w), because of loss of response. Short-term (after the first intensification dose) and the long-term (at the end of follow-up) efficacy of the intensified therapy was analyzed. HarveyBradshaw' s index was used in luminal Crohn' s disease. In fistulizing Crohn' s disease, complete response was defined as closure of all fistulas, and partial response as a 50% or more reduction in the number or the debit of fistulas. Safety was evaluated by collection of adverse effects. Results: We included 33 patients (mean age, 39 years; 50% male; 33% smokers; 60% with ileocolic (L3) disease; 50% with fistulizing (B3) phenotype; 70% with perianal (p) disease). The majority (70%) of the patiens was treated with immunomodulators. The mean follow-up for intensified treatment was 40 weeks (range: 16-72 w). Mean time of IFX exposure before intensification was 12 months (range: 3-29 m). On the short-term, after the first intensification dose, 83% responded (31% complete response, 52% partial response). On the long-term, after the last intensification dose, only 65% were still responding (17% complete response, 48% partial response). One patient suffered an infusion reaction after 36 doses of intensified treatment, which subsided with slower infusion. One patient suffered an episode of herpes zoster, that did not interrupt the treatment. Conclusions: The intensification of IFX therapy is sometimes necessary after a mean drug exposure of one year. A high proportion will initially respond, but 20% of all cases lose effect again a mean of 10 months after intensification. Safety profile of IFX therapy intensification is good, having no severe adverse effects.

Poster Presentations P180 INCREASED THROMBIN GENERATION IN INFLAMMATORY BOWEL DISEASES S. Saibeni 1 , V. Saladino 2 , V. Chantarangkul 2, F. Villa 2 , M. Vecchi 3 , S. Bruno 1 , R. de Franchis 2, C. Sei 2 , P.M. Mannucci 2 , A. Tripodi 2 . 1 Azienda Ospedaliera Fatebenefratelli e Oftalmico, Milan, Italy; 2 IRCCS Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy; 3 IRCCS Policlinico San Donato, San Donato Milanese, Italy Inflammatory Bowel Diseases (IBD) are characterized by an increased thrombotic risk. Endogenous Thrombin Potential (ETP), a parameter of the thrombin generation curve, represents a new tool in the evaluation of thrombotic and bleeding disorders. Aim: to study ETP in IBD patients and to correlate the results with clinical and biochemical features. Materials and Methods: 74 IBD patients (37 ulcerative colitis and 37 Crohn' s disease) and 57 healthy controls enrolled. ETP values, measured with or without thrombomodulin, are expressed as nM thrombin times minutes. Results: in the presence of thrombomodulin, IBD patients with increased C-reactive protein (CRP) had significantly higher mean (± SD) ETP values (1,721.3 ± 458.0 nM·min) than either patients with normal CRP (1,356.6 ± 394.5 nM·min) and controls (1,277.1 ± 402.7 nM·min) (p<0.001). A significant correlation was observed between ETP and CRP (r=0.28, 95% C.I., 0.06-0.48, p=0.015) and erythrocyte sedimentation rate (ESR) (r=0.26, 95% C.I. 0.040.47, p=0.022). ETP values higher than the 95th percentile of control values were significantly more frequent in IBD patients than in controls (RR 1.71, 95% C.I. 1.33-2.20; p<0.002). Conclusions: ETP is increased in IBD patients, markedly in those with increased acute-phase reactants. ETP may help to identify IBD patients at increased thrombotic risk, regardless the underlying causes.

P181 IBDPROSPECT, THE ROMANIAN COMPUTERISED ON-LINE SYSTEM FOR PROSPECTIVE MONITORING OF INFLAMMATORY BOWEL DISEASE R. Iacob, C. Gheorghe, M. Diculescu. Fundeni Clinical Institute, Bucharest, Romania Background: Incidence and prevalence of IBD are rising also in Eastern European countries as life style changes are taking place. Prospective disease monitoring in this region has the perspective of revealing interesting epidemiological data with relationship to disease etiopathogeny. Aim: To establish a nationwide IBD registry for prospective monitoring of this pathology in Romania. Methods: After generating a template of significant variables to take into account, a computer database accessible from different study locations via Internet has been generated. Results: A registry system has been implemented with different study sites and individual study site registry numbers to identify individual IBD cases. Variables concerning epidemiological data, personal medical history, familial medical history, clinical, paraclinical and information concerning the therapy can be recorded, as well as other specific variables. The coordinator of the registry has the ability to define new study sites, new users and new variables which can be grouped in different categories like genetics, serology, histopatology and also do define new variable categories, thus assuring a good prospective flexibility. So far, the registry is functional in two large IBD referral Centers in Romania, in Bucharest and Cluj and 103 IBD cases have been recorded during the study period july-november 2007. Conclusion: The prospective follow-up of IBD in now possible in Romania using a computerised registry, accessible from different locations, thus allowing the study of this pathology on a nationwide basis.

P182 SPECIFIC AND NON SPECIFIC MICROSCOPIC INFLAMMATORY ANORMALITIES MAY EQUALLY AFFECT THE COLORECTUM AND THE TERMINAL ILEUM OF PATIENTS WITH CLINICALLY DIFFERENT SYMPTOM-BASED DIAGNOSIS OF FUNCTIONAL BOWEL DISORDERS A. Marcheggiano, A. Covotta, C. Iannoni, D. Badiali, R. Cantarini, M. Paoletti, N. Pallotta, E. Corazziari. University Sapienza, Rome, Italy Specific and non-specific microscopic inflammatory abnormalities of the colo-rectal mucosa have been reported in IBS. It is not known whether these histological findings can be detected in patients with other Functional Bowel Disorders (FBD) and in the terminal ileum. Aims of this study were 1) to evaluate the histological pattern of the mucosa of the large bowel and terminal ileum in patients referred for FBD, and 2) whether the clinical presentation of the FBD differs according to the site affected by, and the specific or non specific type of, the microscopic