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1126 Prediction of Treatment Failures in Induction of Remission With Oral Mesalamine in Mild-to-Moderately Active Ulcerative Colitis
1125 Oral Tacrolimus Versus Cyclosporine a in Patients With Moderate to Severe Ulcerative Colitis Refractory to Corticosteroids Hiroshi Aoki, Ryuichi Furukawa, Yasuo Suzuki
AGA Abstracts
BACKGROUND: There are limited treatment options for patients with corticosteroid refractory ulcerative colitis (UC). Tacrolimus belongs to a group of medicines known as immunosuppressive agents. Animal models of inflammatory bowel disease and uncontrolled studies in humans suggest that Tacrolimus may be an effective medication for patients with UC. Accordingly, although almost exclusively used in trial cases, Tacrolimus has shown significant efficacy in the suppression of UC relapse. This study compared the efficacy of oral Tacrolimus vs Cyclosporine (Cs)A in patients with UC, refractory to corticosteroids. METHODS: Between January 2006 and January 2011, a total of 113 patients with UC, all corticosteroid refractory were included in this study. The patients were randomly assigned to two groups, CsA (n= 80; 40 male and 40 female, average age 34.7 ± 13.9 years) and Tacrolimus (n=33, 23 male and 10 female, average age 41.4 ± 15.7 years). Lichtiger's clinical activity index (CAI) was applied to assess UC activity and treatment efficacy. Following an initial 14 days of remission induction therapy with CsA (2mg/kg body weight/day, iv) or Tacrolimus (0.05-0.15mg/kg body weight/day), patients who achieved a CAI score of 3 or better were followed for 12 months. During the 12 months follow-up time, maintenance rate of remission was monitored by using the Kaplan-Meier graphs for survival analyses. RESULTS: In the CsA group, the average CAI scores before and after the initial two weeks of treatment were 13.1 ± 2.92 and 5.6 ± 3.35, respectively (P<0.0001). The corresponding CAI scores in the Tacrolimus group were 9.75 ± 3.27 and 5.0±3.84, respectively (P<0.01). The clinical remission rates (CAI = 3 or better) after the initial two weeks of treatment were 30.0% (24 of 80 patients) in the CsA group and 45.4% (15 of 33 patients) in the Tacrolimus group, the difference was not statistically significant (P=0.11). Further, response rates (a decrease in CAI by at least 4 points) were 77.5% (62 of 80 patients) in the CsA group and 69.7% (23 of 33 patients) in the Tacrolimus group. Again, the difference did not reach significance level (P= 0.38). Likewise, the rates of remission maintenance at 12 months were 35.2% in the CsA group and 33.7% in the Tacrolimus group. The difference did not reach significance level (P= 0.26). CONCLUSIONS: In this study involving 113 patients with UC of corticosteroid refractory background, Tacrolimus and CsA showed similar efficacy both in the rate of remission induction and maintenance of remission. 1126 Prediction of Treatment Failures in Induction of Remission With Oral Mesalamine in Mild-to-Moderately Active Ulcerative Colitis Wolfgang Kruis, Ralph Mueller, Roland Greinwald
* p-values derived from χ2-test ** Baseline HI ≤1 vs >1
INTRODUCTION: Though mesalamine (5-ASA) is the mainstay for the treatment of ulcerative colitis (UC), not all patients are sufficiently responding. To improve treatments, it seems useful to define risk factors, which predict failure of 5-ASA to induce remission of UC. AIMS & METHODS: This is a post-hoc analysis of pooled data from three fully published RCT`s1-3 for the induction of remission (Clinical Activity Index [CAI] and Endoscopic Index [EI] acc. to Rachmilewitz) in mild-to-moderately active UC. All studies used the same product (Salofalk granules manufactured by Dr. Falk Pharma GmbH, Freiburg, Germany), the same dosis (3g/day), the same assessments, and very similar protocols. Univariate (UV) analyses were performed using χ2-test for dichotomous parameters (sex, current or former smoker vs non-smoker, Histologic Index ≤ 1 vs >1 at baseline) and for categorical parameters (localization of UC), and using logistic regression for continuous variables. Multivariate (MV) analyses were performed using stepwise logistic regressions to select the relevant risk factors among all parameters. The endpoints of interest were “failing induction of remission”; p<0.05 was considered significant. RESULTS: A total of 531 patients were included into the analyses. Table 1 provides the core results: CONCLUSION: Young age, high baseline CAI, nonsmoker, localization, and elevated baseline CRP have been identified as major parameters in both, UV and MV analyses, which can predict failures in induction of clinical remission; high baseline EI and elevated CRP as predictors for failures to achieve endoscopic remission; and high baseline EI alone as predictor for failures to achieve deep endoscopic remission with 5-ASA in mild-to-moderate active UC. These results may influence clinical decision making and the design of future treatment trials. REFERENCES: 1) Kruis W, et al. Clin Gastroenterol Hepatol. 2003;1(1):36-43. 2) Kruis W, et al. Gut. 2009;58(2):233-40. 3) Marakhouski Y, et al. Aliment Pharmacol Ther. 2005;21(2):133-40. Table 1: P-values and odds ratio estimates for prediction of failure to induce remission (treatment failures)
1127 Infliximab in Steroid-Dependent Ulcerative Colitis: Efficacy and Predictors of Clinical and Endoscopic Remission Alessandro Armuzzi, Daniela Pugliese, Silvio Danese, Gianluca Rizzo, Carla Felice, Manuela Marzo, Gianluca Andrisani, Gionata Fiorino, Italo De Vitis, Alfredo Papa, Gian Ludovico Rapaccini, Luisa Guidi Background and aim: Up to 40% of ulcerative colitis (UC) patients need steroids during their course and 20% of them become steroid-dependent. Immunosuppression with thiopurines is the most used therapy in steroid-dependent UC, but their efficacy is still debated. Data exploring the use of infliximab (IFX) in patients with steroid-dependent UC are scarce. Aims of our study were to evaluate the efficacy and safety of IFX in active steroid-dependent UC and to identify predictive factors of steroid-free clinical remission, mucosal healing and colectomy. Methods: Consecutive patients with active steroid-dependent UC were enrolled and intentionally treated with IFX (standard induction and maintenance treatment). The prospectively designed analyses evaluated: 1) steroid-free clinical remission at 6 and 12 months; 2) mucosal healing (MH) at 12 months; 3) colectomy within 12 months. Clinical remission was defined as Powell-Tuck index of 0 and mucosal healing as a Baron index ≤1. Results: One hundred twenty-six active steroid-dependent UC patients were studied. 70% of patients were taking steroids at baseline, with a median prednisone dose of 25 mg (IQR 15-30). 45% of patients were naïve to thiopurines and 56% were started on concomitant thiopurines. Steroid-free clinical remission was 53% (67/126) and 47% (59/126) at 6 and 12 months, respectively. Thiopurines-naïve status and combination therapy with thiopurines were identified as predictors of steroid-free clinical remission at 6 months (OR:2.9; p=0.03 and OR:3.07; p=0.03, respectively). At 12 months, 32% (41/126) of patients were in steroidfree clinical remission and MH. Thiopurine-naïve status was confirmed as predictor of steroid-free clinical remission and MH (OR:3.6; p=0.01). A higher C-reactive protein (CRP) level after induction was predictive of lower rate of steroid-free clinical remission at 6 (OR:0.1; p=0.0001) and 12 months (OR:0.14; p=0.0005) and steroid-free clinical remission and MH at 12 months (OR:0.17; p=0.009). 12 patients (9.5%) underwent colectomy after a median of 4.7 months (IQR 2.2-8). Patients who were able to spare steroids had a reduced risk of colectomy within the first year (HR:6.3; p=0.005). Adverse events were recorded in 16 patients (13%), but only 10 (8%) withdrew from treatment. Conclusions: IFX appears effective and safe in the treatment of steroid-dependent UC. Thiopurine-naïve patients have higher rates of clinical remission at 6 months and endoscopic remission at 12 months. Combination therapy appears more effective until the first 6 months. Steroid-sparing is protective from colectomy.
S-205
AGA Abstracts
AGA Abstracts
BACKGROUND: There are limited treatment options for patients with corticosteroid refractory ulcerative colitis (UC). Tacrolimus belongs to a group of medicines known as immunosuppressive agents. Animal models of inflammatory bowel disease and uncontrolled studies in humans suggest that Tacrolimus may be an effective medication for patients with UC. Accordingly, although almost exclusively used in trial cases, Tacrolimus has shown significant efficacy in the suppression of UC relapse. This study compared the efficacy of oral Tacrolimus vs Cyclosporine (Cs)A in patients with UC, refractory to corticosteroids. METHODS: Between January 2006 and January 2011, a total of 113 patients with UC, all corticosteroid refractory were included in this study. The patients were randomly assigned to two groups, CsA (n= 80; 40 male and 40 female, average age 34.7 ± 13.9 years) and Tacrolimus (n=33, 23 male and 10 female, average age 41.4 ± 15.7 years). Lichtiger's clinical activity index (CAI) was applied to assess UC activity and treatment efficacy. Following an initial 14 days of remission induction therapy with CsA (2mg/kg body weight/day, iv) or Tacrolimus (0.05-0.15mg/kg body weight/day), patients who achieved a CAI score of 3 or better were followed for 12 months. During the 12 months follow-up time, maintenance rate of remission was monitored by using the Kaplan-Meier graphs for survival analyses. RESULTS: In the CsA group, the average CAI scores before and after the initial two weeks of treatment were 13.1 ± 2.92 and 5.6 ± 3.35, respectively (P<0.0001). The corresponding CAI scores in the Tacrolimus group were 9.75 ± 3.27 and 5.0±3.84, respectively (P<0.01). The clinical remission rates (CAI = 3 or better) after the initial two weeks of treatment were 30.0% (24 of 80 patients) in the CsA group and 45.4% (15 of 33 patients) in the Tacrolimus group, the difference was not statistically significant (P=0.11). Further, response rates (a decrease in CAI by at least 4 points) were 77.5% (62 of 80 patients) in the CsA group and 69.7% (23 of 33 patients) in the Tacrolimus group. Again, the difference did not reach significance level (P= 0.38). Likewise, the rates of remission maintenance at 12 months were 35.2% in the CsA group and 33.7% in the Tacrolimus group. The difference did not reach significance level (P= 0.26). CONCLUSIONS: In this study involving 113 patients with UC of corticosteroid refractory background, Tacrolimus and CsA showed similar efficacy both in the rate of remission induction and maintenance of remission. 1126 Prediction of Treatment Failures in Induction of Remission With Oral Mesalamine in Mild-to-Moderately Active Ulcerative Colitis Wolfgang Kruis, Ralph Mueller, Roland Greinwald
* p-values derived from χ2-test ** Baseline HI ≤1 vs >1
INTRODUCTION: Though mesalamine (5-ASA) is the mainstay for the treatment of ulcerative colitis (UC), not all patients are sufficiently responding. To improve treatments, it seems useful to define risk factors, which predict failure of 5-ASA to induce remission of UC. AIMS & METHODS: This is a post-hoc analysis of pooled data from three fully published RCT`s1-3 for the induction of remission (Clinical Activity Index [CAI] and Endoscopic Index [EI] acc. to Rachmilewitz) in mild-to-moderately active UC. All studies used the same product (Salofalk granules manufactured by Dr. Falk Pharma GmbH, Freiburg, Germany), the same dosis (3g/day), the same assessments, and very similar protocols. Univariate (UV) analyses were performed using χ2-test for dichotomous parameters (sex, current or former smoker vs non-smoker, Histologic Index ≤ 1 vs >1 at baseline) and for categorical parameters (localization of UC), and using logistic regression for continuous variables. Multivariate (MV) analyses were performed using stepwise logistic regressions to select the relevant risk factors among all parameters. The endpoints of interest were “failing induction of remission”; p<0.05 was considered significant. RESULTS: A total of 531 patients were included into the analyses. Table 1 provides the core results: CONCLUSION: Young age, high baseline CAI, nonsmoker, localization, and elevated baseline CRP have been identified as major parameters in both, UV and MV analyses, which can predict failures in induction of clinical remission; high baseline EI and elevated CRP as predictors for failures to achieve endoscopic remission; and high baseline EI alone as predictor for failures to achieve deep endoscopic remission with 5-ASA in mild-to-moderate active UC. These results may influence clinical decision making and the design of future treatment trials. REFERENCES: 1) Kruis W, et al. Clin Gastroenterol Hepatol. 2003;1(1):36-43. 2) Kruis W, et al. Gut. 2009;58(2):233-40. 3) Marakhouski Y, et al. Aliment Pharmacol Ther. 2005;21(2):133-40. Table 1: P-values and odds ratio estimates for prediction of failure to induce remission (treatment failures)
1127 Infliximab in Steroid-Dependent Ulcerative Colitis: Efficacy and Predictors of Clinical and Endoscopic Remission Alessandro Armuzzi, Daniela Pugliese, Silvio Danese, Gianluca Rizzo, Carla Felice, Manuela Marzo, Gianluca Andrisani, Gionata Fiorino, Italo De Vitis, Alfredo Papa, Gian Ludovico Rapaccini, Luisa Guidi Background and aim: Up to 40% of ulcerative colitis (UC) patients need steroids during their course and 20% of them become steroid-dependent. Immunosuppression with thiopurines is the most used therapy in steroid-dependent UC, but their efficacy is still debated. Data exploring the use of infliximab (IFX) in patients with steroid-dependent UC are scarce. Aims of our study were to evaluate the efficacy and safety of IFX in active steroid-dependent UC and to identify predictive factors of steroid-free clinical remission, mucosal healing and colectomy. Methods: Consecutive patients with active steroid-dependent UC were enrolled and intentionally treated with IFX (standard induction and maintenance treatment). The prospectively designed analyses evaluated: 1) steroid-free clinical remission at 6 and 12 months; 2) mucosal healing (MH) at 12 months; 3) colectomy within 12 months. Clinical remission was defined as Powell-Tuck index of 0 and mucosal healing as a Baron index ≤1. Results: One hundred twenty-six active steroid-dependent UC patients were studied. 70% of patients were taking steroids at baseline, with a median prednisone dose of 25 mg (IQR 15-30). 45% of patients were naïve to thiopurines and 56% were started on concomitant thiopurines. Steroid-free clinical remission was 53% (67/126) and 47% (59/126) at 6 and 12 months, respectively. Thiopurines-naïve status and combination therapy with thiopurines were identified as predictors of steroid-free clinical remission at 6 months (OR:2.9; p=0.03 and OR:3.07; p=0.03, respectively). At 12 months, 32% (41/126) of patients were in steroidfree clinical remission and MH. Thiopurine-naïve status was confirmed as predictor of steroid-free clinical remission and MH (OR:3.6; p=0.01). A higher C-reactive protein (CRP) level after induction was predictive of lower rate of steroid-free clinical remission at 6 (OR:0.1; p=0.0001) and 12 months (OR:0.14; p=0.0005) and steroid-free clinical remission and MH at 12 months (OR:0.17; p=0.009). 12 patients (9.5%) underwent colectomy after a median of 4.7 months (IQR 2.2-8). Patients who were able to spare steroids had a reduced risk of colectomy within the first year (HR:6.3; p=0.005). Adverse events were recorded in 16 patients (13%), but only 10 (8%) withdrew from treatment. Conclusions: IFX appears effective and safe in the treatment of steroid-dependent UC. Thiopurine-naïve patients have higher rates of clinical remission at 6 months and endoscopic remission at 12 months. Combination therapy appears more effective until the first 6 months. Steroid-sparing is protective from colectomy.
S-205
AGA Abstracts