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P344 Therapeutic escalation in patients with ulcerative colitis: systematic analysis of the prevalence and risk factors in the Swiss IBD cohort
Clinical: Therapy and observation (P = 0.02). One patient (5%) in the EN group and 5 patients (25%) in the control group required reoperation for recurrence (P = 0.18). The cumulative incidence of reoperation was lower in the EN group vs the control group, the difference not being significant (P = 0.08). Conclusions: The outcomes of this study suggest that EN therapy reduces the incidence of postoperative CD recurrence. P343 TPMT genotyping before thiopurine treatment results in lower leucopenia occurrence in a prospective randomized strategy study in 850 patients with inflammatory bowel disease M.J. Coenen1 , C.J. van Marrewijk1 , L. Derijks2 , S.H. Vermeulen3 , H. Scheffer1 , B. Franke1 , H.-J. Guchelaar4 , D.J. de Jong5 *. 1 Radboud University Nijmegen Medical Centre, Genetics, Nijmegen, Netherlands, 2 Maxima Medical Centre, Clinical Pharmacy, Veldhoven, Netherlands, 3 Radboud University Nijmegen Medical Centre, Epidemiology, Biostatistics and Health Technology, Nijmegen, Netherlands, 4 Leiden University Medical Centre, Clinical Pharmacy and Toxicology, Leiden, Netherlands, 5 Radboud University Nijmegen Medical Centre, Gastroenterology; Topic study group, Nijmegen, Netherlands Background: Thiopurines play an important role in the treatment of IBD. However, over 20% of the patients discontinue therapy due to adverse drug reactions. Leucopenia is a serious side effect, which is associated with thiopurine S-methyltransferase (TPMT) genotype in retrospective studies. Yet, TPMT pharmacogenetics in order to improve safety and efficacy of thiopurine treatment is only used on a limited scale. Our aim was to investigate the value of pre-treatment TPMT genotyping and thiopurine dose adjustments based on genotype on the occurrence of leucopenia. Methods: We performed a prospective randomized trial in thiopurine naïve IBD patients starting thiopurine treatment as part of the Dutch TOPIC study (ClinicalTrials.gov NCT00521950). Patients were randomly assigned to undergo pre-treatment genotyping for three common variants in TPMT (TPMT*2, *3A and *3C) or to undergo standard treatment with azathioprine or 6-mercaptopurine (6-MP). The standard initial dose was 2.0 to 2.5 mg/kg bodyweight for azathioprine and 1.0 to 1.5 mg/kg for 6-MP. In the genotype group, patients that carried one of the TPMT variants were recommended a dose reduction of 50% and for patients with a variant on both alleles a maximum of 10% of the standard dose was recommended. The primary endpoint to assess the effect of pre-treatment genotyping was the rate of leucopenia <3.0×109 /l in the first 5 months after treatment initiation between both arms. Results: 850 patients were randomized (62% with Crohn’s disease; 38% with ulcerative colitis) and 64% of these patients were treated with azathioprine and 36% with 6-MP. In both the genotype guided group (n = 428) and the standard treatment group (n = 422) 42 patients (10%) carried at least one genetic variant in the TPMT gene. Finally 832 patients started with a thiopurine and 65 of these patients (8%) developed leucopenia <3.0×109 /l. Overall, the rate of leucopenia was not significant different between both groups (7.2% versus 8.1%). However, in the group of intermediate metabolizers, we found a statistically significant reduction of the number of leucopenia cases in the group that underwent pre-treatment genotyping versus standard treatment (2.4% (n = 1) versus 21.4% (n = 9), p-value 0.003). Conclusions: In this prospective pharmacogenetic study in thiopurine naïve IBD patients, we demonstrated that pretreatment TPMT genotyping results in a significant lower occurrence of leucopenia in patients with at least one variant in the TPMT gene, which is the case in 10% of the population.
S147 P344 Therapeutic escalation in patients with ulcerative colitis: systematic analysis of the prevalence and risk factors in the Swiss IBD cohort E. Safroneeva1 *, S. Vavricka2 , N. Fournier3 , A. Straumann4 , A. Schoepfer5 . 1 University of Bern, Institute of Social and Preventive Medicine, Bern, Switzerland, 2 University Hospital Zurich, Gastroenterology and Hepatology, Zurich, Switzerland, 3 University of Lausanne, Institute of Social and Preventive Medicine, Lausanne, Switzerland, 4 University Hospital Basel, Gastroenterology and Hepatology, Switzerland, 5 University Hospital Lausanne / CHUV, Gastroenterology and Hepatology, Lausanne, Switzerland Background: To date, studies that systematically assess therapeutic escalation in patients with ulcerative colitis (UC) are scarce. We aimed to assess the percentage of UC patients undergoing therapeutic escalation over time and to identify escalation-associated risk factors. Methods: Data from the Swiss IBD Cohort Study were analyzed. Eighty percent of patients were recruited in hospitals and 20% in private practices. The percentage of patients undergoing treatment with the following regimens relative to disease duration was assessed: 5-aminosalicylates (5-ASA), steroids, immunomodulators (IM) (azathioprine and 6-mercaptopurine), anti-TNF drugs (infliximab, adalimumab), and calcineurininhibitors (cyclosporine, tacrolimus). Patients that were not treated with medical therapy and those that underwent UCrelated surgery were also evaluated. Non-parametric data are presented as median and interquartile range. Results: A total of 901 UC patients were included (females: 45.3%, median age: 41 [32 52] years, median age at diagnosis: 31 [24 40] years, disease duration: 6 [2 14] years). Fortytwo percent of patients presented with pancolitis, 42% with left-sided colitis, and 16% with proctitis. The proportions of patients that were either not treated with therapy or else treated with various regimens are as follows: 5-ASA 28.0%, steroids and/or IM 51.0%, anti-TNF and/or calcineurin inhibitors 18.3%, surgery 2.3%, no therapy 0.4% for disease duration of 0 to 2 years; 5-ASA 18.9%, steroids and/or IM 49.5%, antiTNF and/or calcineurin inhibitors 28.6%, surgery 2.0%, no therapy 1.0% for disease duration of 3 6 years; 5-ASA 16.3%, steroids and/or IM 57.5%, anti-TNF and/or calcineurin inhibitors 20.4%, surgery 5.0%, no therapy 0.8% for disease duration of 7 14 years; 5-ASA 15.0%, steroids and/or IM 60.9%, anti-TNF and/or calcineurin inhibitors 9.7%, surgery 14.0%, no therapy 1.4% for disease 15 years. Young age at UC diagnosis (OR 0.955, 95% CI 0.929 0.981, p = 0.001) as well as pancolitis (OR 2.404, 95% CI 1.261 4.584, p = 0.007) were the main risk factors for a rapid therapeutic step-up requiring treatment with antiTNF drugs and/or calcineurin inhibitors within the first two years after UC diagnosis. Conclusions: Less than 20% of UC patients were treated solely by 5-ASA after a disease duration of 3 years. Young age at disease onset and pancolitis are the major risk factors requiring a rapid step-up within the first two years of disease course. P345 The natural history of azathioprine therapy for steroid-dependent ulcerative colitis: a Korean study S.K. Park1 *, S.K. Yang1 , B.D. Ye1 , K.J. Kim1 , D.H. Yang1 , K.W. Jung1 , S.H. Park1 , J.W. Kim1 , J.S. Byeon1 , S.J. Myung1 , J.H. Kim1 . 1 Asan Medical Center, Gastroenterology, Seoul, South Korea Background: Azathioprine is widely used for the treatment of inflammatory bowel disease. In contrast to Crohn’s disease, relatively few studies have addressed the therapeutic efficacy of azathioprine in patients with ulcerative colitis (UC). We aimed to evaluate efficacy of azathioprine in Korean patients with steroid-dependent UC.
S147 P344 Therapeutic escalation in patients with ulcerative colitis: systematic analysis of the prevalence and risk factors in the Swiss IBD cohort E. Safroneeva1 *, S. Vavricka2 , N. Fournier3 , A. Straumann4 , A. Schoepfer5 . 1 University of Bern, Institute of Social and Preventive Medicine, Bern, Switzerland, 2 University Hospital Zurich, Gastroenterology and Hepatology, Zurich, Switzerland, 3 University of Lausanne, Institute of Social and Preventive Medicine, Lausanne, Switzerland, 4 University Hospital Basel, Gastroenterology and Hepatology, Switzerland, 5 University Hospital Lausanne / CHUV, Gastroenterology and Hepatology, Lausanne, Switzerland Background: To date, studies that systematically assess therapeutic escalation in patients with ulcerative colitis (UC) are scarce. We aimed to assess the percentage of UC patients undergoing therapeutic escalation over time and to identify escalation-associated risk factors. Methods: Data from the Swiss IBD Cohort Study were analyzed. Eighty percent of patients were recruited in hospitals and 20% in private practices. The percentage of patients undergoing treatment with the following regimens relative to disease duration was assessed: 5-aminosalicylates (5-ASA), steroids, immunomodulators (IM) (azathioprine and 6-mercaptopurine), anti-TNF drugs (infliximab, adalimumab), and calcineurininhibitors (cyclosporine, tacrolimus). Patients that were not treated with medical therapy and those that underwent UCrelated surgery were also evaluated. Non-parametric data are presented as median and interquartile range. Results: A total of 901 UC patients were included (females: 45.3%, median age: 41 [32 52] years, median age at diagnosis: 31 [24 40] years, disease duration: 6 [2 14] years). Fortytwo percent of patients presented with pancolitis, 42% with left-sided colitis, and 16% with proctitis. The proportions of patients that were either not treated with therapy or else treated with various regimens are as follows: 5-ASA 28.0%, steroids and/or IM 51.0%, anti-TNF and/or calcineurin inhibitors 18.3%, surgery 2.3%, no therapy 0.4% for disease duration of 0 to 2 years; 5-ASA 18.9%, steroids and/or IM 49.5%, antiTNF and/or calcineurin inhibitors 28.6%, surgery 2.0%, no therapy 1.0% for disease duration of 3 6 years; 5-ASA 16.3%, steroids and/or IM 57.5%, anti-TNF and/or calcineurin inhibitors 20.4%, surgery 5.0%, no therapy 0.8% for disease duration of 7 14 years; 5-ASA 15.0%, steroids and/or IM 60.9%, anti-TNF and/or calcineurin inhibitors 9.7%, surgery 14.0%, no therapy 1.4% for disease 15 years. Young age at UC diagnosis (OR 0.955, 95% CI 0.929 0.981, p = 0.001) as well as pancolitis (OR 2.404, 95% CI 1.261 4.584, p = 0.007) were the main risk factors for a rapid therapeutic step-up requiring treatment with antiTNF drugs and/or calcineurin inhibitors within the first two years after UC diagnosis. Conclusions: Less than 20% of UC patients were treated solely by 5-ASA after a disease duration of 3 years. Young age at disease onset and pancolitis are the major risk factors requiring a rapid step-up within the first two years of disease course. P345 The natural history of azathioprine therapy for steroid-dependent ulcerative colitis: a Korean study S.K. Park1 *, S.K. Yang1 , B.D. Ye1 , K.J. Kim1 , D.H. Yang1 , K.W. Jung1 , S.H. Park1 , J.W. Kim1 , J.S. Byeon1 , S.J. Myung1 , J.H. Kim1 . 1 Asan Medical Center, Gastroenterology, Seoul, South Korea Background: Azathioprine is widely used for the treatment of inflammatory bowel disease. In contrast to Crohn’s disease, relatively few studies have addressed the therapeutic efficacy of azathioprine in patients with ulcerative colitis (UC). We aimed to evaluate efficacy of azathioprine in Korean patients with steroid-dependent UC.