P384 Predictive factors of response to prolonged intravenous corticosteroids in patients with acute severe ulcerative colitis

Clinical: Therapy & observation age, affected area, duration of illness, total dose of PSL administered 4 and 2 weeks before introduction of TAC, CRP and Hb on admission, CAI before TAC administration, and time required for the blood TAC level to reach the target level, but no significant difference was noted in any item. However, a significant difference was noted in the CAI score at the time when the blood TAC level reached the target level between the clinical remission (8±3.2) and non-remission (12±2.6) groups (p < 0.05). When the interval estimation of the mean CAI score was compared between those on admission and at the time of reaching the target TAC level, the reduction rate was 41.7 55.1% in the clinical remission group and 13.8 37% in the non-remission group. Conclusions: The rate of reduction of the CAI score from that before TAC administration to that at the time of reaching the target blood TAC level may be an important predictor of the effect. P383 Predictive factors of early infliximab infusion reactions in inflammatory bowel disease C. Duron1 , A. Buisson1 *, B. Pereira2 , G. Bommelaer1 . 1 University Hospital Estaing, Gastroenterology department, Clermont-Ferrand, France, 2 DRCI, Biostatistics Unit, Clermont-Ferrand, France Background: Anti-TNF agents including infliximab (IFX), a chimeric antibody, are the most potent therapies in inflammatory bowel diseases (IBD). Early IFX Infusion Reaction (EIIR) is rare, but is a serious complication in IBD patients, and could lead to drug withdrawal and consequently could impact the therapeutic strategy. The role of premedication remains uncertain. We aimed to establish predictors of EIIR in IBD patients and to assess the impact of premedication. Methods: Patients, disease and perfusions characteristics, collected for all IFX infusions performed in our IBD Unit, were retrieved from electronic charts from 2008 to 2013. The EIIR were defined as events related to IFX infusions occurring within the two hours of the infusion. Univariate and multivariate analysis were performed taking into account the inter-patients and intra-patients variability. Results: Among the 80 CD patients included, 23 (28.8%) experienced EIIR. Age, prior history of intestinal resection, atopy or allergy, familial history of IBD, type of IBD, disease location, disease extent or disease duration were not predictive of EIIR. In univariate analysis, non-structuring non fistulising CD was predictive of EIIR (26.4% vs 52.2%, p = 0.03). This result was not confirmed by multivariate analysis. Of 1107 infusions, we observed 38 EIIR (3.4%). In univariate analysis, the first four infusions (26.4% vs 52.6%, p = 0.002) and the reintroduction of IFX after drug discontinuation (17.2% vs 29.0%, p = 0.001) were predictive of EIIR. Multivariate analysis confirms that the reintroduction of IFX after drug discontinuation is a major risk factor of EIIR but not the first four infusions. A premedication (anti-histaminic or hydrocortisone) or concomitant therapies (5-ASA, steroids, thiopurines or methotrexate) did not decrease the risk of EIIR. Overall, 16 of the 23 patients experiencing EIIR (69.5%) had to discontinue IFX therapy. Conclusions: EIIR is a major event in the history of IBD patients treated by IFX as it leads to drug discontinuation and thus limits considerably the therapeutic armamentarium available. The reintroduction of IFX after drug discontinuation is the major risk of EIIR. The efficacy of premedication remains uncertain and might be limited only to this high risk situation. The measurement of anti-drug antibodies could be an interesting topic to predict the occurrence of EIIR in IBD patients for whom IFX was reintroduced after drug discontinuation.

S225 P384 Predictive factors of response to prolonged intravenous corticosteroids in patients with acute severe ulcerative colitis D.J. Lee *, M.E. Song, S.J. Park, S.P. Hong, T.I. Kim, W.H. Kim, J.H. Cheon. Yonsei University College of Medicine, Department of Internal Medicine and Institute of Gastroenterology, Seoul, South Korea Background: Severe ulcerative colitis (UC) can still be a life threatening condition despite intensive medical management and early colectomy. Intravenous corticosteroid therapy is used as a bridge therapy for acute severe UC, but it’s appropriate duration of administration and timing of response assessment has not yet been defined. The objective of this study was to evaluate the clinical predictive factors after prolonged intravenous steroid therapy in acute severe patients with UC. Methods: We retrospectively evaluated a total of 173 cases among 131 patients, who were hospitalized and received intravenous corticosteroid therapy for acute exacerbations of severe UC between January 2005 and September 2012 from at Severance Hospital, Seoul, South Korea. Patients who achieved remission or had treatment failure were excluded from treatment response assessment at 5 days after intravenous steroid therapy. The remaining 130 case with equivocal response, who were neither early-responders nor non-responders, were classified into late responders (who finally obtained remission; 115 cases) and non-responders (who ultimately underwent rescue therapy; 15 cases). We compared between the 2 groups on the basis of 7 days for the determination of the response assessment time. Results: On univariate analysis, there was a significant negative correlation of late-responders with initial modified Truelove score, initial Mayo score, initial partial Mayo score, modified Truelove score at 5 days, and partial Mayo score at 5 days. Previous attack count and platelet counts were negatively correlated on the basis of 5 days. On the other hand, delta of partial Mayo score (partial Mayo score at 5 days initial partial Mayo score), hemoglobin and albumin levels showed a positive correlation at 5 days, hemoglobin level was positively correlated at the time of 7 days. A multivariable analysis showed that partial Mayo score at 5 days [OR 0.085 (0.013 0.539), p = 0.009], delta of partial Mayo score [OR 5.595 (1.583 19.771), p = 0.008], previous attack count [OR 0.181 (0.039 0.850), p = 0.030] and hemoglobin level [OR 4.227 (1.109 16.112), p = 0.035] were independent predictive values at 5 days. At 7 days, partial Mayo score at 7 days [OR 0.080 (0.012 0.525), p = 0.009], hemoglobin [OR 6.271 (1.437 27.366), p = 0.015] were significantly associated with response to prolonged steroid response. Conclusions: Partial Mayo score, delta of partial Mayo score, previous attack count and hemoglobin level were the meaningful independent parameters among the predictors for prolonged intravenous steroid treatment response. These factors may help physicians determine whether to continue the steroids for equivocal responders. P385 Population pharmacokinetic modelling of vedolizumab in patients with ulcerative colitis or Crohn’s disease M. Rosario1 *, N. Dirks2 , M. Gastonguay2 , I. Fox1 , A. Milton1 . 1 Takeda Pharmaceuticals International Company, Clinical Pharmacology, Cambridge, United States, 2 Metrum Research Group LLC, Biotechnology, Tariffville, United States Background: Vedolizumab (VDZ), currently in development for treating ulcerative colitis (UC) and Crohn’s disease (CD), exhibits target-mediated drug disposition. Described here are a VDZ population pharmacokinetic (PK) model, an estimation of typical VDZ parameter values, and effects of covariates that may be predictors of VDZ PK variability.