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Su1132 Toxicity and Mortality Related to the Use of Ciclosporin in Steroid Refractory Ulcerative Colitis: A Multicentric Nationwide Study (ENEIDA)
on by a single surgeon was reviewed. The cohort was divided into 2 groups based on exposure to biologics before surgery: Group A had been treated with biologics and Group B was not treated with biologics. Patient demographics, disease severity and cumulative rates of postoperative outcomes within 30 days of surgery were reviewed. These variables were also compared in 3 subgroups of Group A: infliximab alone group, infliximab in combination with other biologics group, and other biologics excluding infliximab group. Associations between Groups A and B and postoperative outcomes were analyzed using Fisher's exact and t-test. Associations between each of the biologics subgroups (in comparison to Group B) and covariates were analyzed using multinomial logistic regression model, and ANOVA model, followed by pairwise post-hoc analysis, with adjustment for multiple comparisons. Results: The study cohort comprised 458 consecutive patients (median age 33; 55% males). Group A included 213 (47%) patients and Group B included 245 (53%) patients. In Group A, 126 (59%) had been on infliximab alone, 51 (24%) had been on infliximab and other biologics, and 36 (17%) had been treated with adalimumab and/or certolizumab without infliximab. Patient demographics and disease severity in the two groups were similar, except Group A had a higher incidence of preoperative immunomodulator use (98% vs 88%, p=0.0002), and lower rates of internal penetrating disease behavior (37% vs 51%; p=0.005) and preoperative enteric perforation (23% vs 36%; p=0.002). Surgery in Group A was not associated with significantly higher risk of overall postoperative morbidity and infectious complications. However, compared to Group B, subgroup analyses demonstrated an increased risk of postoperative intraabdominal infections in the infliximab-alone group (10% vs 4%, OR 3.5, p=0.047). Rates of readmission (14% vs 7%, p=0.06) and ileus (14% vs 7%, p=0.06) after surgery were also higher in the infliximab-alone group although these did not reach statistical significance. On multivariate analysis, postoperative hospitalization stay and time to tolerance of diet was higher in the infliximab alone group. Conclusion: Preoperative biologic therapy was not associated with an overall increased risk of postoperative complications in our CD cohort. However, subgroup analysis showed increased risks of postoperative intraabdominal infections, time to tolerance of diet and postoperative hospitalization stay in the infliximab-alone treated group.
Incidence rate of lymphoma by the cumulative duration of exposure to thiopurines Su1132 Toxicity and Mortality Related to the Use of Ciclosporin in Steroid Refractory Ulcerative Colitis: A Multicentric Nationwide Study (ENEIDA) Ingrid Ordás, Eugeni Domenech, Valle García-Sánchez, Mireia Peñalva, Alex Cañas, Olga Merino, Fernando Fernández-Bañares, Fernando Gomollon, Isabel Vera, Ana Gutiérrez, Esther Garcia-Planella, Javier P. Gisbert, Mariam Aguas, Elena Gento, Fernando Muñoz, Maddi Aguirresarobe, Carmen Muñoz, Luis Fernandez, Pere Vilar, Xavier Calvet, Manuel Barreiro-de Acosta, Carlos E. Jiménez, Miguel A. Montoro, Joaquin Hinojosa, Cristina Saro, Alberto Mir, Luisa De-Castro, Mariana F. Garcia-Sepulcre, Fernando Bermejo, Maria Esteve Introduction: A recent randomized controlled trial comparing ciclosporin (CyA) with infliximab (IFX) in the setting of steroid refractory ulcerative colitis (SR-UC) has shown similar efficacy and safety for both treatments. However, the safety profile of CyA remains to be a concern in some countries. Aims: 1) To evaluate the toxicity and mortality related to the use of CyA in patients with severe SR-UC flares in clinical practice 2) To compare CyA adverse events (AEs) with other treatment regimens (IFX and surgery) with the same indication. Patients and Methods: Multicenter, community-based cohort study. Patients were identified using a prospectively maintained database (ENEIDA registry). Data collected included: age, sex, disease extent, treatment (CyA, IFX, surgery and/or combination of these), dose, treatment duration, AEs, concomitant use of immunomodulators, prophylactic treatment in case of triple immunosuppression, clinical remission, colectomy rate at 1 and 5 years and mortality rate related to the steroid-refractory flare. To avoid an inclusion bias, all participating centers reviewed the cases of death diagnosed with UC and its causes since 1990. Results: From 5783 UC patients, 473 (8.2%) met the inclusion criteria (SR-UC). All cases received treatment with corticosteroids. Treatment regimens for induction of remission were the following: CyA (n=210; 47.1%), IFX (n=44; 9.5%), CyA-IFX (n=24; 5.2%), IFXCyA (n=3; 0.6%), Colectomy (n=92; 19.8%), CyA-Colectomy (n=59; 12,7%), IFX-Colectomy (n=10; 2.2%), CyA-IFX-Colectomy (n=12; 2.6%), IFX-CyA-Colectomy (n=2; 0.4%). Global remission rate was 73.6%. The mortality rate associated to CyA and the global mortality rate was 2.5% and 10% respectively (52% related to colectomy), varying from 0 to 13.5% according to different centers. There was no difference between CyA and IFX-related mortality (n=5, 2.5% vs. n=1, 2.3%; p=1, respectively), neither between CyA-colectomy and IFXcolectomy (n=6, 10% vs. n=0, 0%; p=0.27). Patients treated with CyA presented less AEs [n=18, 9.5% (infections 3.7%)] than IFX treated patients [n=12, 27.3%; p=0.002 (infections 11.4%)]. From patients treated with colectomy (without having received medical rescue therapy; either CyA or IFX), 34.8% presented AEs (n=23), infections being the more frequent (n=7; 10.6%). Conclusions: we provide safety results of the largest series of patients treated with CyA for severe SR-UC. The lower rate of AEs associated with CyA compared to IFX and a similar mortality rate between both treatment strategies give support to the use of CyA as a first-line rescue therapy in cases of SR-UC. Colectomy in cases of severe SR-UC should be performed in experienced centers due to the elevated mortality rate associated with the procedure.
Su1134 Prediction of Dose of Tacrolimus Required for Remission Induction of Ulcerative Colitis Patients Sakiko Hiraoka, Jun Kato, Toshihiro Inokuchi, Asuka Nakarai, Tomoko Hirakawa, Mitsuhiro Akita, Keita Harada, Hiroyuki Okada, Kazuhide Yamamoto Background and Aims: Calcineurin inhibitors such as cyclosporine A and tacrolimus have been shown to be effective for treatment of steroid-dependent or steroid-refractory ulcerative colitis (UC) patients with moderate to severe activity. Tacrolimus is usually taken orally with efficacy, and therefore, it can be prescribed for outpatients. However, large variety in dose required for reaching sufficient trough levels among individuals has made the administration for outpatients difficult. This study aimed to identify factors that regulated the dose of tacrolimus required for achieving sufficient trough levels for remission induction of UC patients. Methods: Data on all patients with moderate to severe UC who had been treated with tacrolimus at our hospitals from September 2006 to October 2012, were analyzed. No patients had renal function disorders, and patients who were readministered tacrolimus were excluded. The initial oral dose of tacrolimus was 0.05-0.15 mg/kg/day. Trough concentrations were measured and doses were adjusted with the aim of achieving whole blood trough concentrations of 10-15 ng/ml. Medical charts provided clinical information including demographic data, such as age, gender, and duration of the disease, severity of disease, and extent of disease. In addition, we examined medications (5-aminosalicylates, corticoisteroids, immunomodulator use), bowel movements (frequency/day), diet (fasting or not), and laboratory data (WBC, CRP) at starting tacrolimus. Tacrolimus dose was analyzed with correction by body weight. Results: We administered tacrolimus to 47 UC patients (24 (51%) male, median (range) age of 37(12-70) years) during the study period. Of the 47 patients, 41 (87%) achieved a clinical remission or response with the tacrolimus therapy. Median daily dose of tacrolimus required for sufficient trough levels was 0.19 (0.07-0.42) mg/kg. Because the dose required for each patient showed bimodal distribution, patients were divided into two groups by the required dose ( , 0.2mg/kg or ≥ 0.2mg/kg). Age, gender, and CRP (. 1.5 mg/dL) differed significantly between the two groups. Multivariate analysis revealed that male (OR = 7.10; 95% CI, 1.35-50.0) and CRP . 1.5 mg/dL (OR = 7.24; 95% CI, 1.39-53.2) were independent factors for the required dose ≥ 0.2mg/kg. The remission rate and adverse events did not differ significantly between the two groups. Conclusions: The required dose of tacrolimus for remission induction of UC showed bimodal distribution and predictive factors for requirement of high dose were identified. For further generalization of tacrolimus, the additional analysis including genetic polymorphisms on the pharmacokinetics is required.
Su1133 Influence of Biologic Agents on Short-Term Postoperative Complications in Patients With Crohn's Disease: A Prospective, Single-Surgeon Cohort Study Cheryl C. Lau, Marla Dubinsky, Gil Y. Melmed, Eric A. Vasiliauskas, Dermot P. McGovern, Dror Berel, Zuri A. Murrell, Andrew Ippoliti, David Q. Shih, Manreet Kaur, Stephan R. Targan, Phillip Fleshner Aim: Biologic therapy is an essential component in the management of patients with Crohn's disease (CD). Current evidence on the influence of biologic therapy on postoperative outcomes is conflicting. Method: A prospectively maintained CD registry of patients operated
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AGA Abstracts
AGA Abstracts
199,204. Majority were Caucasians (75%), males (93%) with median age at inclusion of 60 years. Among the included patients, 4,734 used thiopurines with median duration of one year. Numbers of lymphoma cases identified were 119 and 18 among non-users and while using thiopurines respectively. The incidence rate of lymphoma among those who never used thiopurines was 0.6 compared to 0.9, 1.6, 1.6, 5, 8.9 per 1000 person-year for the 1st, 2nd, 3th, 4th and .4 years of thiopurine use respectively (Figure). The incidence rates of the fourth and more than four years were significantly different from the incidence rate of non-users, yielding HR of lymphoma of 8 and 14 for the fourth year and more than four year of thiopurines use respectively (p ,0.001). Conclusion: In this nationwide cohort of UC patients, the incidence rate of lymphoma significantly increased after the third year of cumulative exposure to thiopurines.
Incidence rate of lymphoma by the cumulative duration of exposure to thiopurines Su1132 Toxicity and Mortality Related to the Use of Ciclosporin in Steroid Refractory Ulcerative Colitis: A Multicentric Nationwide Study (ENEIDA) Ingrid Ordás, Eugeni Domenech, Valle García-Sánchez, Mireia Peñalva, Alex Cañas, Olga Merino, Fernando Fernández-Bañares, Fernando Gomollon, Isabel Vera, Ana Gutiérrez, Esther Garcia-Planella, Javier P. Gisbert, Mariam Aguas, Elena Gento, Fernando Muñoz, Maddi Aguirresarobe, Carmen Muñoz, Luis Fernandez, Pere Vilar, Xavier Calvet, Manuel Barreiro-de Acosta, Carlos E. Jiménez, Miguel A. Montoro, Joaquin Hinojosa, Cristina Saro, Alberto Mir, Luisa De-Castro, Mariana F. Garcia-Sepulcre, Fernando Bermejo, Maria Esteve Introduction: A recent randomized controlled trial comparing ciclosporin (CyA) with infliximab (IFX) in the setting of steroid refractory ulcerative colitis (SR-UC) has shown similar efficacy and safety for both treatments. However, the safety profile of CyA remains to be a concern in some countries. Aims: 1) To evaluate the toxicity and mortality related to the use of CyA in patients with severe SR-UC flares in clinical practice 2) To compare CyA adverse events (AEs) with other treatment regimens (IFX and surgery) with the same indication. Patients and Methods: Multicenter, community-based cohort study. Patients were identified using a prospectively maintained database (ENEIDA registry). Data collected included: age, sex, disease extent, treatment (CyA, IFX, surgery and/or combination of these), dose, treatment duration, AEs, concomitant use of immunomodulators, prophylactic treatment in case of triple immunosuppression, clinical remission, colectomy rate at 1 and 5 years and mortality rate related to the steroid-refractory flare. To avoid an inclusion bias, all participating centers reviewed the cases of death diagnosed with UC and its causes since 1990. Results: From 5783 UC patients, 473 (8.2%) met the inclusion criteria (SR-UC). All cases received treatment with corticosteroids. Treatment regimens for induction of remission were the following: CyA (n=210; 47.1%), IFX (n=44; 9.5%), CyA-IFX (n=24; 5.2%), IFXCyA (n=3; 0.6%), Colectomy (n=92; 19.8%), CyA-Colectomy (n=59; 12,7%), IFX-Colectomy (n=10; 2.2%), CyA-IFX-Colectomy (n=12; 2.6%), IFX-CyA-Colectomy (n=2; 0.4%). Global remission rate was 73.6%. The mortality rate associated to CyA and the global mortality rate was 2.5% and 10% respectively (52% related to colectomy), varying from 0 to 13.5% according to different centers. There was no difference between CyA and IFX-related mortality (n=5, 2.5% vs. n=1, 2.3%; p=1, respectively), neither between CyA-colectomy and IFXcolectomy (n=6, 10% vs. n=0, 0%; p=0.27). Patients treated with CyA presented less AEs [n=18, 9.5% (infections 3.7%)] than IFX treated patients [n=12, 27.3%; p=0.002 (infections 11.4%)]. From patients treated with colectomy (without having received medical rescue therapy; either CyA or IFX), 34.8% presented AEs (n=23), infections being the more frequent (n=7; 10.6%). Conclusions: we provide safety results of the largest series of patients treated with CyA for severe SR-UC. The lower rate of AEs associated with CyA compared to IFX and a similar mortality rate between both treatment strategies give support to the use of CyA as a first-line rescue therapy in cases of SR-UC. Colectomy in cases of severe SR-UC should be performed in experienced centers due to the elevated mortality rate associated with the procedure.
Su1134 Prediction of Dose of Tacrolimus Required for Remission Induction of Ulcerative Colitis Patients Sakiko Hiraoka, Jun Kato, Toshihiro Inokuchi, Asuka Nakarai, Tomoko Hirakawa, Mitsuhiro Akita, Keita Harada, Hiroyuki Okada, Kazuhide Yamamoto Background and Aims: Calcineurin inhibitors such as cyclosporine A and tacrolimus have been shown to be effective for treatment of steroid-dependent or steroid-refractory ulcerative colitis (UC) patients with moderate to severe activity. Tacrolimus is usually taken orally with efficacy, and therefore, it can be prescribed for outpatients. However, large variety in dose required for reaching sufficient trough levels among individuals has made the administration for outpatients difficult. This study aimed to identify factors that regulated the dose of tacrolimus required for achieving sufficient trough levels for remission induction of UC patients. Methods: Data on all patients with moderate to severe UC who had been treated with tacrolimus at our hospitals from September 2006 to October 2012, were analyzed. No patients had renal function disorders, and patients who were readministered tacrolimus were excluded. The initial oral dose of tacrolimus was 0.05-0.15 mg/kg/day. Trough concentrations were measured and doses were adjusted with the aim of achieving whole blood trough concentrations of 10-15 ng/ml. Medical charts provided clinical information including demographic data, such as age, gender, and duration of the disease, severity of disease, and extent of disease. In addition, we examined medications (5-aminosalicylates, corticoisteroids, immunomodulator use), bowel movements (frequency/day), diet (fasting or not), and laboratory data (WBC, CRP) at starting tacrolimus. Tacrolimus dose was analyzed with correction by body weight. Results: We administered tacrolimus to 47 UC patients (24 (51%) male, median (range) age of 37(12-70) years) during the study period. Of the 47 patients, 41 (87%) achieved a clinical remission or response with the tacrolimus therapy. Median daily dose of tacrolimus required for sufficient trough levels was 0.19 (0.07-0.42) mg/kg. Because the dose required for each patient showed bimodal distribution, patients were divided into two groups by the required dose ( , 0.2mg/kg or ≥ 0.2mg/kg). Age, gender, and CRP (. 1.5 mg/dL) differed significantly between the two groups. Multivariate analysis revealed that male (OR = 7.10; 95% CI, 1.35-50.0) and CRP . 1.5 mg/dL (OR = 7.24; 95% CI, 1.39-53.2) were independent factors for the required dose ≥ 0.2mg/kg. The remission rate and adverse events did not differ significantly between the two groups. Conclusions: The required dose of tacrolimus for remission induction of UC showed bimodal distribution and predictive factors for requirement of high dose were identified. For further generalization of tacrolimus, the additional analysis including genetic polymorphisms on the pharmacokinetics is required.
Su1133 Influence of Biologic Agents on Short-Term Postoperative Complications in Patients With Crohn's Disease: A Prospective, Single-Surgeon Cohort Study Cheryl C. Lau, Marla Dubinsky, Gil Y. Melmed, Eric A. Vasiliauskas, Dermot P. McGovern, Dror Berel, Zuri A. Murrell, Andrew Ippoliti, David Q. Shih, Manreet Kaur, Stephan R. Targan, Phillip Fleshner Aim: Biologic therapy is an essential component in the management of patients with Crohn's disease (CD). Current evidence on the influence of biologic therapy on postoperative outcomes is conflicting. Method: A prospectively maintained CD registry of patients operated
S-407
AGA Abstracts
AGA Abstracts
199,204. Majority were Caucasians (75%), males (93%) with median age at inclusion of 60 years. Among the included patients, 4,734 used thiopurines with median duration of one year. Numbers of lymphoma cases identified were 119 and 18 among non-users and while using thiopurines respectively. The incidence rate of lymphoma among those who never used thiopurines was 0.6 compared to 0.9, 1.6, 1.6, 5, 8.9 per 1000 person-year for the 1st, 2nd, 3th, 4th and .4 years of thiopurine use respectively (Figure). The incidence rates of the fourth and more than four years were significantly different from the incidence rate of non-users, yielding HR of lymphoma of 8 and 14 for the fourth year and more than four year of thiopurines use respectively (p ,0.001). Conclusion: In this nationwide cohort of UC patients, the incidence rate of lymphoma significantly increased after the third year of cumulative exposure to thiopurines.