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S1142 The Pattern and Outcome of Acute Severe Colitis
gentle compression. Data were analyzed using nonresponder imputation (NRI). Results: Of 945 pts in CARE, 18% (171) had draining fistulas at baseline. Of the fistula cohort, 64% were female, 98% were white, median age was 35 yrs, median weight was 64 kg, 84% had prior immunosuppressant use, 43% had prior steroid use, 27% had used prior CD-related antibiotics, and 63% had prior exposure to IFX (26 of 108 were primary nonresponders to IFX). Complete fistula healing results at Wks 12 and 20 are provided (table). One-quarter of all pts with fistulas at baseline had healed fistulas at Wk 20. Conclusions: ADA therapy led to clinically meaningful rates of complete fistula healing at Wk 12, which were sustained through Wk 20. ADA was effective in anti-TNF-naïve pts and pts who had failed therapy with IFX. ADA was well-tolerated, with safety consistent with prior reports in CD. References 1. Colombel J-F, et al. Gastroenterology. 2007;132:52-65. 2. Colombel J-F, et al. Am J Gastroenterol. 2008;103(Suppl 1):S417.
S1142 The Pattern and Outcome of Acute Severe Colitis Lotte C. Dinesen, Alissa J. Walsh, Marijana Nedeljkovic Protic, Graham A. Heap, Fraser Cummings, Bryan F. Warren, Bruce George, Neil Mortensen, Simon Travis Background: The prognosis of acute severe ulcerative colitis (ASC) influences therapeutic decisions, but data on prevalence or long-term outcome are few. Methods: To assess the prevalence of ASC defined by Truelove and Witts' (TW) criteria and determine whether outcome is related to disease activity on admission, the likelihood of recurrence and longterm prognosis, a systematic review of all patients with UC diagnosed in Oxford was performed. Results: 750 patients with UC (median follow up 12.7yr, range 0-648mo) were evaluated out of a total cohort of 1853 patients. 24.8% (186/750) had at least one admission for ASC (294 admissions in 186 patients). Overall, 12% (93/750) had a colectomy, compared to 39.8% (74/186) of patients with one or more episodes of ASC (p<0.0001) and 3.4% (19/ 564) who had no admission. The colectomy rate on first admission (37/186, 19.9%) was lower than on the second or subsequent admissions (OR 2.35, 95% CI 1.33-4.14, p=0.003), being 29.0%, 36.6%, 38.2% after two, three, or subsequent episodes respectively. It was 8.5% (11/129) if patients had one TW criterion in addition to >6 bloody bowel motions/ day, compared to 31% (29/94) if two additional criteria were present and 48% (29/60) if three additional criteria were present (p=1.2x10-6; OR 4.01, 95% CI 2.24-7.19 one criterion vs two or more). Conclusions: A quarter of all patients with ulcerative colitis experience at least one episode of ASC; 20% come to colectomy on the first admission, but 40% after two admissions. The likelihood of colectomy is related to biological severity on admission.
S1145 Long-Term Impact of Clostridium difficile On Inflammatory Bowel Disease Adeeti Chiplunker, Ashwin N. Ananthakrishnan, Dawn B. Beaulieu, Amar S. Naik, Yelena Zadvornova, Susan Skaros, Kathryn Johnson, Lilani P. Perera, David G. Binion, Mazen Issa Introduction: Increased incidence and virulence of Clostridium difficile (C diff) has been reported over past 5 years. IBD pts have been impacted disproportionately with increased rates of hospitalization, colectomy and mortality. Long-term impact of C diff infection in IBD is unknown. Methods: This was a retrospective study of all IBD pts with positive stool toxin during 2005-6 from a single tertiary center who had 1 year followup after C diff infection. Demographic data and disease characteristics were collected. The main outcomes of interest were: 1) escalation of drug therapy, 2) need for hospitalization related to IBD flare and 3) need for surgery. Each patient served as their own control, as we examined the rates of hospitalization and IBD drug therapy in the year immediately preceding the C diff infection (control period) compared with the year following C diff infection. Results: A total of 87 IBD pts (51 F, 36 M) with C diff were identified. The mean age was 41.7 years (range 20-88 years) with a mean age of disease onset of 29.8 years (range 8-71 years). Fifty-three pts (60.9%) had Crohn's disease (CD), 31 (35.6%) had ulcerative colitis (UC) and 3 had indeterminate colitis. Colectomy occurred in 10.3% of pts (9/87) following C diff infection. The mean difference in hospitalizations between the year prior and the year following C diff infection was 0.89 (95% CI 0.51 - 1.27). 41.3% of pts (36/87) had no difference in the number of hospitalizations while 8% had fewer hospitalizations in the year following infection. However, 46% of pts (40/87) had more hospitalizations in the year following C diff infection (range 1-9). Over half (46/87; 53%) of IBD pts with C diff required an escalation in their IBD medical therapy. This included initiation of biologic therapy (26%;23/87), escalation of current biologic (8%; 7/87), escalation or initiation of azathioprine / 6-MP (11.5%;10/ 87) or methotrexate (7%;6/87). Recurrent C diff occurred in 11.5% of pts (10/87)documented by toxin assay. No deaths occurred during the 1 year followup. Conclusions: Within one year following C diff infection, over half of IBD pts required an escalation in IBD treatment. Further studies assessing the impact of C diff pathogenicity on IBD disease activity are warranted.
S1143 Azathioprine/Biological Therapy Does Prevent Surgery But Not Reoperation in Smokers with Crohn's Disease Peter L. Lakatos, Tamas Szamosi, Zsofia Czegledi, Janos Papp, Eszter Schafer, Gyula David, Pandur Tunde, Zsuzsanna Erdelyi, Janos Banai, Laszlo Lakatos Background/Aim: Smoking may alter the natural course of Crohn's disease (CD). Smokers are more likely to develop complications, relapses and have a greater risk for surgery. In contrast smoking might improve the disease course in ulcerative colitis (UC). Our aim was to assess the combined effect of smoking and immunomodulator (azathioprine, AZA/ biological) treatment on the risk of intestinal resection and re-operation in CD and colectomy in UC. Patients/Methods: 502 IBD patients were analyzed (CD: 277, 46.2% males, age at diagnosis: 28.7 (SD 13.2) years, mean duration: 9.5(7.8) years; UC: 227, 48.5% males, age at diagnosis: 34.3 (SD 14.5) years, mean duration: 11.3 (10.4) years). Patients' medical records have been analyzed retrospectively and patients were asked for smoking status at diagnosis and during follow-up by standardized questionnaires. Results: Smoking was present in 47.1% in CD and 13.2% in UC. 133 CD patients (48%) underwent at least one bowel resection, while at least one reoperation was necessary in 44 (15.9%). In univariate analysis disease location (p=0.004), behavior (p<0.0001), AZA or AZA/biological use prior to surgery (OR: 0.19 and 0.227, p<0.0001 for both) and smoking (OR: 1.79, p=0.018) were associated with the risk for surgery. Perianal disease (OR: 3.83, p=0.001) and frequent relapses (OR: 5.85, p<0.0001) but not smoking status or AZA or AZA/biological use after first surgery were predictive for re-operation. Smoking (OR: 1.91), AZA or AZA/IFX use prior to surgery (OR: 0.19) and disease behavior (OR: 3.13) were independently associated with risk for surgery in a logistic regression analysis. The deleterious effect of smoking was most striking in stenosing disease (pLogRank: 0.028). AZA use decreased the risk for first surgery (p<0.0001 for both)but not re-operation in patients with and without smoking also in a Kaplan-Meier analysis and LogRank/Breslow tests. In UC, 12 (5.3%) patients had colectomy. Disease location (p=0.001) but not smoking status was associated with risk for colectomy. Of note, none of the patients with colectomy smoked compared to 14% of patients without colectomy (p=NS). Conclusion: Our data suggest that AZA/biological therapy reduces the risk for first operation but not reoperation in CD in CD in both smokers and none-smokers. The deleterious effect of smoking was most pronounced in patients with stenosing disease.
S1146 Predictors of Post-Operative Outcome of Perianal Fistula Surgery in Patients with Crohn's Disease Alexandra Gutierrez, Ernesto R. Drelichman, Robert A. Oster, Talha Malik Background: Crohn's disease (CD) is a chronic transmural process which is complicated >30% of the time by fistulas. A combined medical and surgical approach is the cornerstone of treatment for CD associated perianal fistulas(PF). Aim: To identify clinical and serologic predictors of post-operative outcome of PF surgery in patients with CD. Methods: 30 consecutive CD patients over 18 who underwent surgical closure of PF (fistulotomy, flap procedure or diversion) from 2005-2008 were identified. Laboratory, clinical and historic data were extrapolated from the medical records. Bivariate and multivariate logistic regression analyses were used to identify variables associated with fistula closure at 3 and 6 months. Statistical significance was assessed at P < 0.05. Results: 30% of patients were African American and 77% of patients were female. 23% of patients smoked and 53% had elevated rectal disease activity (RDA). 33% had anal stenosis (AS). 87% of the patients were on immunomodulators at the time of surgery. 57% were on an anti tumor necrosis factor antibody (aTNF). Mean body mass index (BMI) was 27.6 kg/m2. 53% of patients underwent fistulotomy and 23% of patients had diversion or flap procedure. Bivariate analysis revealed that increased RDA and AS were significant negative predictors of outcome at 3 months (P= 0.008 and P=0.012 respectively) and at 6 months (P=0.006 and P=0.029 respectively).Type of surgery was significant only at 3 months (P=0.033). Patients on an aTNF had a lower likelihood of not having achieved closure of the fistula at 3 months post-op (P=0.045 OR= 0.162 95% CI 0.027-0.961). No statistical significance was identified based on BMI, duration of CD, smoking status, number or type of fistulas, or history of steroid use. Type of surgical intervention was a significant predictor when all three procedures were compared to outcome together, but not when compared individually. PF was closed in 19 (63%) and 15 (50%) of the 30 patients at 3 and 6 months respectively. Both clinically significant and significant variables from the bivariate analysis were included in multivariate logistic regression models. When controlling for BMI, number of years with the diagnosis of CD and number of prior surgeries, only elevated RDA predicted a decreased likelihood of fistula closure at both 3
S1144 Adalimumab Induces Sustained Fistula Healing in Both Anti-TNF-Naïve and Anti-TNF-Experienced Patients with Crohn's Disease: The Care Trial Robert Lofberg, Edouard Louis, Walter Reinisch, Martina Kron, Anne Camez, Anne Robinson, Paul F. Pollack Introduction: Adalimumab (ADA), a fully human anti-tumor necrosis factor (anti-TNF) monoclonal antibody, has been shown to induce and maintain remission in patients (pts) with Crohn's disease (CD). Fistulizing disease complicates the course of CD in up to 40% of pts. The efficacy of ADA in complete fistula closure for up to 3 years (yrs) was demonstrated previously in CHARM and its open-label extension (ADHERE), in which one-third of pts with fistulas had complete healing at the end of CHARM, approximately 60% of whom maintained healing through 2 additional yrs of treatment in ADHERE.1,2 Methods: In the Crohn's Pts Treated With ADA: Results of a Safety and Efficacy Study (CARE), we evaluated efficacy and safety of ADA in a large population of pts whose treatment approximated usual clinical practice. Pts with Harvey-Bradshaw Index (HBI) scores >7 enrolled in this multicenter, open-label, European trial. Pts received induction therapy of 160-mg/80-mg ADA at Weeks (Wks) 0/2, followed by ADA 40-mg every-other-wk maintenance therapy through at least Wk 20 (pts with flares/nonresponse could receive 40 mg weekly at/after Wk 12). Endpoints in CARE included fistula healing and response, and here we evaluated ADA's ability to induce fistula healing in pts naïve to biologic therapy, as well as those who had failed therapy with infliximab (IFX). Fistulas were considered healed if they did not drain upon
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with ulcerative colitis overestimate their CRC risk. Risk perception is not a significant predictor of non-adherence. Despite their concerns about colon cancer risk, most patients would not choose colectomy for the level of CRC risk associated with either low grade (20%) or high grade dysplasia (40%).
S1142 The Pattern and Outcome of Acute Severe Colitis Lotte C. Dinesen, Alissa J. Walsh, Marijana Nedeljkovic Protic, Graham A. Heap, Fraser Cummings, Bryan F. Warren, Bruce George, Neil Mortensen, Simon Travis Background: The prognosis of acute severe ulcerative colitis (ASC) influences therapeutic decisions, but data on prevalence or long-term outcome are few. Methods: To assess the prevalence of ASC defined by Truelove and Witts' (TW) criteria and determine whether outcome is related to disease activity on admission, the likelihood of recurrence and longterm prognosis, a systematic review of all patients with UC diagnosed in Oxford was performed. Results: 750 patients with UC (median follow up 12.7yr, range 0-648mo) were evaluated out of a total cohort of 1853 patients. 24.8% (186/750) had at least one admission for ASC (294 admissions in 186 patients). Overall, 12% (93/750) had a colectomy, compared to 39.8% (74/186) of patients with one or more episodes of ASC (p<0.0001) and 3.4% (19/ 564) who had no admission. The colectomy rate on first admission (37/186, 19.9%) was lower than on the second or subsequent admissions (OR 2.35, 95% CI 1.33-4.14, p=0.003), being 29.0%, 36.6%, 38.2% after two, three, or subsequent episodes respectively. It was 8.5% (11/129) if patients had one TW criterion in addition to >6 bloody bowel motions/ day, compared to 31% (29/94) if two additional criteria were present and 48% (29/60) if three additional criteria were present (p=1.2x10-6; OR 4.01, 95% CI 2.24-7.19 one criterion vs two or more). Conclusions: A quarter of all patients with ulcerative colitis experience at least one episode of ASC; 20% come to colectomy on the first admission, but 40% after two admissions. The likelihood of colectomy is related to biological severity on admission.
S1145 Long-Term Impact of Clostridium difficile On Inflammatory Bowel Disease Adeeti Chiplunker, Ashwin N. Ananthakrishnan, Dawn B. Beaulieu, Amar S. Naik, Yelena Zadvornova, Susan Skaros, Kathryn Johnson, Lilani P. Perera, David G. Binion, Mazen Issa Introduction: Increased incidence and virulence of Clostridium difficile (C diff) has been reported over past 5 years. IBD pts have been impacted disproportionately with increased rates of hospitalization, colectomy and mortality. Long-term impact of C diff infection in IBD is unknown. Methods: This was a retrospective study of all IBD pts with positive stool toxin during 2005-6 from a single tertiary center who had 1 year followup after C diff infection. Demographic data and disease characteristics were collected. The main outcomes of interest were: 1) escalation of drug therapy, 2) need for hospitalization related to IBD flare and 3) need for surgery. Each patient served as their own control, as we examined the rates of hospitalization and IBD drug therapy in the year immediately preceding the C diff infection (control period) compared with the year following C diff infection. Results: A total of 87 IBD pts (51 F, 36 M) with C diff were identified. The mean age was 41.7 years (range 20-88 years) with a mean age of disease onset of 29.8 years (range 8-71 years). Fifty-three pts (60.9%) had Crohn's disease (CD), 31 (35.6%) had ulcerative colitis (UC) and 3 had indeterminate colitis. Colectomy occurred in 10.3% of pts (9/87) following C diff infection. The mean difference in hospitalizations between the year prior and the year following C diff infection was 0.89 (95% CI 0.51 - 1.27). 41.3% of pts (36/87) had no difference in the number of hospitalizations while 8% had fewer hospitalizations in the year following infection. However, 46% of pts (40/87) had more hospitalizations in the year following C diff infection (range 1-9). Over half (46/87; 53%) of IBD pts with C diff required an escalation in their IBD medical therapy. This included initiation of biologic therapy (26%;23/87), escalation of current biologic (8%; 7/87), escalation or initiation of azathioprine / 6-MP (11.5%;10/ 87) or methotrexate (7%;6/87). Recurrent C diff occurred in 11.5% of pts (10/87)documented by toxin assay. No deaths occurred during the 1 year followup. Conclusions: Within one year following C diff infection, over half of IBD pts required an escalation in IBD treatment. Further studies assessing the impact of C diff pathogenicity on IBD disease activity are warranted.
S1143 Azathioprine/Biological Therapy Does Prevent Surgery But Not Reoperation in Smokers with Crohn's Disease Peter L. Lakatos, Tamas Szamosi, Zsofia Czegledi, Janos Papp, Eszter Schafer, Gyula David, Pandur Tunde, Zsuzsanna Erdelyi, Janos Banai, Laszlo Lakatos Background/Aim: Smoking may alter the natural course of Crohn's disease (CD). Smokers are more likely to develop complications, relapses and have a greater risk for surgery. In contrast smoking might improve the disease course in ulcerative colitis (UC). Our aim was to assess the combined effect of smoking and immunomodulator (azathioprine, AZA/ biological) treatment on the risk of intestinal resection and re-operation in CD and colectomy in UC. Patients/Methods: 502 IBD patients were analyzed (CD: 277, 46.2% males, age at diagnosis: 28.7 (SD 13.2) years, mean duration: 9.5(7.8) years; UC: 227, 48.5% males, age at diagnosis: 34.3 (SD 14.5) years, mean duration: 11.3 (10.4) years). Patients' medical records have been analyzed retrospectively and patients were asked for smoking status at diagnosis and during follow-up by standardized questionnaires. Results: Smoking was present in 47.1% in CD and 13.2% in UC. 133 CD patients (48%) underwent at least one bowel resection, while at least one reoperation was necessary in 44 (15.9%). In univariate analysis disease location (p=0.004), behavior (p<0.0001), AZA or AZA/biological use prior to surgery (OR: 0.19 and 0.227, p<0.0001 for both) and smoking (OR: 1.79, p=0.018) were associated with the risk for surgery. Perianal disease (OR: 3.83, p=0.001) and frequent relapses (OR: 5.85, p<0.0001) but not smoking status or AZA or AZA/biological use after first surgery were predictive for re-operation. Smoking (OR: 1.91), AZA or AZA/IFX use prior to surgery (OR: 0.19) and disease behavior (OR: 3.13) were independently associated with risk for surgery in a logistic regression analysis. The deleterious effect of smoking was most striking in stenosing disease (pLogRank: 0.028). AZA use decreased the risk for first surgery (p<0.0001 for both)but not re-operation in patients with and without smoking also in a Kaplan-Meier analysis and LogRank/Breslow tests. In UC, 12 (5.3%) patients had colectomy. Disease location (p=0.001) but not smoking status was associated with risk for colectomy. Of note, none of the patients with colectomy smoked compared to 14% of patients without colectomy (p=NS). Conclusion: Our data suggest that AZA/biological therapy reduces the risk for first operation but not reoperation in CD in CD in both smokers and none-smokers. The deleterious effect of smoking was most pronounced in patients with stenosing disease.
S1146 Predictors of Post-Operative Outcome of Perianal Fistula Surgery in Patients with Crohn's Disease Alexandra Gutierrez, Ernesto R. Drelichman, Robert A. Oster, Talha Malik Background: Crohn's disease (CD) is a chronic transmural process which is complicated >30% of the time by fistulas. A combined medical and surgical approach is the cornerstone of treatment for CD associated perianal fistulas(PF). Aim: To identify clinical and serologic predictors of post-operative outcome of PF surgery in patients with CD. Methods: 30 consecutive CD patients over 18 who underwent surgical closure of PF (fistulotomy, flap procedure or diversion) from 2005-2008 were identified. Laboratory, clinical and historic data were extrapolated from the medical records. Bivariate and multivariate logistic regression analyses were used to identify variables associated with fistula closure at 3 and 6 months. Statistical significance was assessed at P < 0.05. Results: 30% of patients were African American and 77% of patients were female. 23% of patients smoked and 53% had elevated rectal disease activity (RDA). 33% had anal stenosis (AS). 87% of the patients were on immunomodulators at the time of surgery. 57% were on an anti tumor necrosis factor antibody (aTNF). Mean body mass index (BMI) was 27.6 kg/m2. 53% of patients underwent fistulotomy and 23% of patients had diversion or flap procedure. Bivariate analysis revealed that increased RDA and AS were significant negative predictors of outcome at 3 months (P= 0.008 and P=0.012 respectively) and at 6 months (P=0.006 and P=0.029 respectively).Type of surgery was significant only at 3 months (P=0.033). Patients on an aTNF had a lower likelihood of not having achieved closure of the fistula at 3 months post-op (P=0.045 OR= 0.162 95% CI 0.027-0.961). No statistical significance was identified based on BMI, duration of CD, smoking status, number or type of fistulas, or history of steroid use. Type of surgical intervention was a significant predictor when all three procedures were compared to outcome together, but not when compared individually. PF was closed in 19 (63%) and 15 (50%) of the 30 patients at 3 and 6 months respectively. Both clinically significant and significant variables from the bivariate analysis were included in multivariate logistic regression models. When controlling for BMI, number of years with the diagnosis of CD and number of prior surgeries, only elevated RDA predicted a decreased likelihood of fistula closure at both 3
S1144 Adalimumab Induces Sustained Fistula Healing in Both Anti-TNF-Naïve and Anti-TNF-Experienced Patients with Crohn's Disease: The Care Trial Robert Lofberg, Edouard Louis, Walter Reinisch, Martina Kron, Anne Camez, Anne Robinson, Paul F. Pollack Introduction: Adalimumab (ADA), a fully human anti-tumor necrosis factor (anti-TNF) monoclonal antibody, has been shown to induce and maintain remission in patients (pts) with Crohn's disease (CD). Fistulizing disease complicates the course of CD in up to 40% of pts. The efficacy of ADA in complete fistula closure for up to 3 years (yrs) was demonstrated previously in CHARM and its open-label extension (ADHERE), in which one-third of pts with fistulas had complete healing at the end of CHARM, approximately 60% of whom maintained healing through 2 additional yrs of treatment in ADHERE.1,2 Methods: In the Crohn's Pts Treated With ADA: Results of a Safety and Efficacy Study (CARE), we evaluated efficacy and safety of ADA in a large population of pts whose treatment approximated usual clinical practice. Pts with Harvey-Bradshaw Index (HBI) scores >7 enrolled in this multicenter, open-label, European trial. Pts received induction therapy of 160-mg/80-mg ADA at Weeks (Wks) 0/2, followed by ADA 40-mg every-other-wk maintenance therapy through at least Wk 20 (pts with flares/nonresponse could receive 40 mg weekly at/after Wk 12). Endpoints in CARE included fistula healing and response, and here we evaluated ADA's ability to induce fistula healing in pts naïve to biologic therapy, as well as those who had failed therapy with infliximab (IFX). Fistulas were considered healed if they did not drain upon
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with ulcerative colitis overestimate their CRC risk. Risk perception is not a significant predictor of non-adherence. Despite their concerns about colon cancer risk, most patients would not choose colectomy for the level of CRC risk associated with either low grade (20%) or high grade dysplasia (40%).