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P311 Adalimumab treatment is associated with improved quality of life in pediatric Crohn's disease
Clinical: Diagnosis and outcome how adherence with individual 5-ASA treatments may impact direct medical costs, through prevented relapses, in the United Kingdom (UK). Methods: A 1-year decision analytic budget impact model was developed, combining data from a UK-based adherence study of 5-ASA treatments with a chart review study on UC costs by relapse status in the UK. The model calculates rates of disease relapses, remissions, and associated costs, based on adherence rates of each 5-ASA medication. The model also allows users to run simulations of relative changes in treatment utilization to show the associated budget impact from the perspective of the National Health Service (NHS). Results: Higher adherence rates (48.3% for MMX MultiMatrix System® [MMX] mesalamine; 40.7% for delayed release mesalamine [DRM] 800 mg; 36.7% for modified release mesalamine [MRM]; 31.8% for controlled release mesalamine [CRM] 1000 mg; 29.7% for controlled release mesalamine [CRM] 500 mg; 29.6% for delayed release mesalamine [DRM] 400 mg; 27.8% for balsalazide) were associated with lower hospitalisation rates (6.6%; 7.3%; 7.7%; 8.1%; 8.3%; 8.3%; and 8.5%, respectively), lower annual hospitalisation costs (£330; £365; £383; £404; £414; £414; and £422, respectively), and lower other medical costs, excluding 5-ASAs (£282; £292; £298; £305; £307; £308; and £310, respectively). The model showed that a hypothetical move from the current utilization mix of 5-ASA treatments to the 5-ASA with the highest adherence rate could save the NHS approximately £92,800 annually per 1,000 UC patients. Conclusions: As non-adherence in UC is associated with costly medical resource utilization, significant cost-offsets could be achieved within the NHS by favouring the 5-ASA treatment with the highest adherence rate. P310 Added value of anti CBir-1 antibodies to differentiate IBD unclassified from ulcerative colitis O. Ben-Bassat1 *, W. Xu2 , J.M. Stempak3 , M.S. Silverberg1 , G. Van Assche1 . 1 Mount Sinai Hospital, Gastroenterology, Toronto, Canada, 2 University of Toronto, Dalla Lana School of Public Health, Toronto, Canada, 3 Mount Sinai Hospital, Zane Cohen Centre for Digestive Diseases, Toronto, Canada Background: Serological markers have been applied with some success to reclassify patients with inflammatory bowel disease, type unclassified (IBDU) to Crohn’s disease (CD) or ulcerative colitis (UC). Addition of anti-OmpC and anti-I2 to pANCA and ASCA antibodies in a serological panel has not been able to improve the discriminative model. Since a diagnosis of IBDU still represents a major challenge when surgical management is considered, we attempted to identify a characteristic profile of patients with IBDU using a panel of serological markers. In addition, we constructed a model to specifically identify a diagnosis of IBDU in patients with colonic IBD. Methods: We performed a cross-sectional analysis of patients with IBDU (42 patients) ascertained through Mount Sinai Hospital IBD Centre in Toronto. Serological profiles (ASCA IgA/IgG, pANCA, anti-OmpC, anti-C-Bir1 and anti-I2) of these subjects were compared with the profiles of 617 subjects with CD and 420 with UC. IBD type and disease location were confirmed using the criteria of the NIDDK IBDGC phenotyping manual and the Montreal Classification. Univariate logistic regression models were applied to assess the association of single serological markers and IBD phenotypes. Multivariate analysis (MVA) was applied to assess the combined serological effects, adjusting for clinical factors such as age and gender. The discriminative value of the MVA model was expressed as area under the curve (AUC). Results: By univariate analysis, all of the serological markers tested showed significantly different positivity rates across the three groups (CD, UC, IBDU; p < 0.001). Logistic regression MVA
S133 models were performed to identify those with CD, UC or IBDU conditioned on disease location. A model containing ASCA, pANCA and anti-C-Bir1 (AUC=0.81) differentiated IBDU from CD. Anti-CBir-1 and ASCA discriminated IBDU from E2 UC (AUC=0.71) and E3 UC (AUC=0.66), respectively. Anti-OmpC or anti-I2 were not significantly useful in any of the MVA models. Conclusions: The presence of anti-CBir-1 and ASCA and a negative pANCA favors CD over IBDU. Anti-CBir1 positivity has moderate predictive capacity to identify IBDU as compared to UC. The limited ability of anti-OmpC and anti-I2 to discriminate IBDU is confirmed. Validation of anti-CBir-1 as a marker for IBDU in larger cohorts is needed. P311 Adalimumab treatment is associated with improved quality of life in pediatric Crohn’s disease J.C. Escher1 *, G. Veereman-Wauters2 , W. Crandall3 , F.M. Ruemmele4 , A. Lazar5 , M. Yang5 , M. Skup5 , P.M. Mulani5 , J. Chao5 , R.B. Thakkar5 , J. Hyams6 . 1 Erasmus MC-Sophia Children’s Hospital, Rotterdam, Netherlands, 2 UZ Brussels, Brussels, Belgium, 3 Nationwide Children’s Hospital, Columbus, OH, United States, 4 Hˆ opital Necker-Enfants Malades, Paris, France, 5 Abbott Laboratories, Abbott Park, IL, United States, 6 Connecticut Children’s Medical Center, Hartford, CT, United States Background: Adalimumab (ADA) has been shown to induce response and remission in moderate/severe pediatric Crohn’s disease (CD). We aimed to assess the effect of ADA treatment on quality of life (QOL) in pediatric patients (pts) with CD. Methods: IMAgINE 1 was a 52-week (wk), multi-center, doubleblind study assessing efficacy and safety of ADA in pts aged 6 17 years with moderate to severe CD (Pediatric CD Activity Index [PCDAI] >30) failing prior therapy, including infliximab. Following 4 wks of open-label induction, 188 pts were randomized 1:1 to standard dose (20 mg, bodyweight [BW] <40 kg, or 40 mg, BW 40 kg) or low dose (10 mg, BW <40 kg, or 20 mg, BW 40 kg) double-blind ADA every other wk. After wk 12, pts who experienced flare or nonresponse could switch to blinded weekly dosing and to standard dose open label therapy. To assess QOL, pts 10 years (N = 176) completed the IMPACT III, a 35-item questionnaire with scores ranging from 35 (poor) to 175 (best), at baseline and wks 12, 26, and 52. A change of 10.8 has been shown to indicate clinical improvement. Within group changes from baseline were assessed using paired t-tests. Changes from baseline were compared between dose groups using ANCOVA (adjusting for anti-TNF exposure, wk 4 response, and baseline IMPACT III score). LOCF was used for pts who discontinued or dose escalated.
Figure: Mean change from baseline in total IMPACT III score.
Results: At baseline, no significant differences were observed between dose groups in demographics, mean PCDAI scores, and prior anti-TNF exposure. The low dose group exhibited higher mean IMPACT III scores at baseline (117.7±15.5 vs. 111.6±18.7, P = 0.018). Both groups demonstrated significant improvements in mean IMPACT III scores at wks 12, 26, and 52 (figure). Improvements were observed in each domain, particularly in the bowel symptoms domain (4.7 4.8 change from baseline
S134 by week 12 in both dose groups). The effect was most pronounced in anti-TNF naïve pts and early responders. The standard dose group demonstrated slightly more improvement, but differences were not statistically significant. Conclusions: ADA treatment was associated with improved QOL in pediatric pts with CD by wk 12 and remained over the 52week study. P312 Acutec: differential diagnosis using computed tomography L. Plastaras1 *, S. Koch2 , L. Vuitton1 , E. Nedeva3 , V. di Martino4 , E. Delabrousse3 . 1 University Hospital of Besan¸con, Gastroenterology, Besan¸con, France, 2 University Hospital of Besan¸con, Gastroenterology, Besan¸con, France, 3 University Hospital of Besan¸con, Radiology, Besan¸con, France, 4 University Hospital of Besan¸con, Hepatology, Besan¸con, France Background: Etiological diagnosis of acute colitis (AC) is difficult, requiring bacteriologic, endoscopic, histopathological and outcome examinations. The aim of this work was to investigate the performance of Computed tomography (CT) to identify the cause of AC and study a new sign, the flat colon sign. Methods: This monocentric retrospective observational study included all consecutive patients admitted to the Gastroenterology department of the University Hospital of Besan¸ con from January 2006 to September 2010. All patients had AC with a clearly identified cause and all had had an abdominal CT scan. CT were retrospectively analyzed in a blinded test and result was then compaird with final etiological diagnosis. We studied the literature for all CT signs and we described a sign, not previously described in the literature: the flat colon sign. It was defined by a complete emptiness of the colonic lumen. Results: During the study period, 1452 patients were hospitalized for AC. Of them, 1247 were excluded because they didn’t undergo CT, or the cause of colitis remained uncertain. Study final population included 105 patients. CT identified 6 signs of inflammatory colitis (n = 43): comb sign, lymph nodes, abscesses, fibrofatty infiltration, involvement of the small bowel, and absence of flat colon sign. Multivariate analysis identified 3 signs: comb sign (OR = 15.16, [95% CI: 2.19 105.10], p = 0.006), small bowel involvement (OR = 6.35, [95% CI: 1.11 36.29], p = 0.037), and lymph nodes (OR = 16.66, [95% CI: 4.94 56.21], p < 0.001. Five signs were associated with infectious colitis (n = 35): continuous distribution, flat colon sign, fat stranding, and absence of comb sign and lymph nodes. Multivariate analysis identified 3 signs: flat colon sign (OR = 12.32 [95% CI: 1.68 90.15], p = 0.013), absence of fat stranding (OR = 3.85, [95% CI: 1.30 11.11], p = 0.014), and of comb sign (OR = 5.88 [95% CI: 1.18 33.33], p = 0.031). Five signs were associated with ischemic colitis (n = 21): fat stranding infiltration, and absence of lymph node, continuous distribution, comb sign, and small bowel involvement. Given the small number of patients in the ischemic colitis group, no multivariate analysis was performed. Conclusions: CT appears as a powerful tool to identify specific sign of each etiology of AC. CT is useful to distinguish inflammatory colitis from infectious colitis, particularly when considering the flat colon sign. A larger prospective study should be conducted to confirm these results.
Poster presentations P313 A composite serological panel predicts burden of inflammation in Crohn’s disease O. Ben-Bassat1 *, S. Lockton2 , F. Princen2 , J.M. Stempak3 , G. Van Assche1 , S. Singh2 , M.S. Silverberg1 . 1 Mount Sinai Hospital, Gastroenterology, Toronto, Canada, 2 Prometheus Labs, San Diego, United States, 3 Mount Sinai Hospital, Zane Cohen Centre for Digestive Diseases, Toronto, Canada Background: There remains a void in identifying biomarkers that can be used to measure the burden of inflammation in inflammatory bowel disease (IBD). Advances in therapeutic approaches suggest that mucosal healing is the ideal goal, however, currently endoscopic evaluation is the only accurate way to monitor this. CRP and fecal calprotectin have some utility but also several flaws. A multi-marker diagnostic panel containing inflammatory markers and serum antibodies was therefore examined to determine its potential utility as a measure of burden of inflammation. Methods: 174 patients with Crohn’s disease (CD) were evaluated with serological markers (ASCA-A and G, ANCA, pANCA, anti-OmpC, CBir1, A4-Fla2 and FlaX) and inflammatory markers (CRP, SAA, ICAM, VCAM, and VEGF) (Prometheus Laboratories, San Diego, CA). All had endoscopic assessment within 1 year of serum collection. Endoscopy reports were scored according to severity and disease extent and location. Analysis of variance (ANOVA) tests were applied to individual markers, and further location-specific marker patterns were analyzed to create a “marker signature” for each location and severity. An inflammatory index score was created by first entering each inflammatory marker to their respective reference range and, per subject, calculating the score as follows: (CRP + SAA)/2 + (ICAM + VCAM)/2 + VEGF. Results: The inflammatory index was significantly and positively associated with CD severity (p = 5.5×10 6 ). This index was independent of disease location (p = 0.335). 3 markers were significantly associated with increasing severity: CRP (p = 1.3×10 7 ), SAA (p = 8.8×10 5 ) & VEGF (p = 0.044). Similarly, five serological markers were associated with severity: ASCA-A (p = 0.021), ANCA (p = 0.041), CBir1 (p = 0.012), A4-Fla2 (p = 0.013) & FlaX (0.019). Colonic involvement was associated with higher VEGF (p = 0.0046) and CRP (p = 0.04), suggesting increased systemic inflammation. Disease location was also significantly associated with higher titres of ASCA-A (p = 0.001), ASCA-G (p = 0.004), Fla2 (p = 0.042) and FlaX (p = 0.021). There was a trend towards higher flagellin titres in left colonic CD. Conclusions: In this cohort, we demonstrated a significant correlation between CD disease severity, assessed endoscopically, with an inflammatory index score based on a panel of serum inflammatory markers. Furthermore, each disease location exhibited a unique serological marker pattern. This multi-marker diagnostic panel may be a useful instrument to assessing the burden of endoscopic disease severity in CD. P314 Accuracy of fecal calprotectin in the assessment of post-operative endoscopic recurrence in patients with Crohn’s disease e1 , G. Boschetti1 *, D. Moussata1 , A.-L. Charlois2 , B. Flouri´ S. Nancey1 . 1 Lyon-Sud Hospital, Gastroenterology, PierreB´ enite, France, 2 Lyon-Sud Hospital, Statistics, Pierre-B´ enite, France Background: Endoscopic post-operative recurrence is frequent in Crohn’s disease (CD) and is highly predictive of further clinical recurrence. Aims: i) to assess the performance of fecal calprotectin (fCal) to discriminate in CD patients who had undergone an ileo-colonic resection those who experienced an endoscopic recurrence from those who did not; ii) to determine the best threshold of fCal capable to distinguish CD patients with or without a post-operative endoscopic recurrence.
S133 models were performed to identify those with CD, UC or IBDU conditioned on disease location. A model containing ASCA, pANCA and anti-C-Bir1 (AUC=0.81) differentiated IBDU from CD. Anti-CBir-1 and ASCA discriminated IBDU from E2 UC (AUC=0.71) and E3 UC (AUC=0.66), respectively. Anti-OmpC or anti-I2 were not significantly useful in any of the MVA models. Conclusions: The presence of anti-CBir-1 and ASCA and a negative pANCA favors CD over IBDU. Anti-CBir1 positivity has moderate predictive capacity to identify IBDU as compared to UC. The limited ability of anti-OmpC and anti-I2 to discriminate IBDU is confirmed. Validation of anti-CBir-1 as a marker for IBDU in larger cohorts is needed. P311 Adalimumab treatment is associated with improved quality of life in pediatric Crohn’s disease J.C. Escher1 *, G. Veereman-Wauters2 , W. Crandall3 , F.M. Ruemmele4 , A. Lazar5 , M. Yang5 , M. Skup5 , P.M. Mulani5 , J. Chao5 , R.B. Thakkar5 , J. Hyams6 . 1 Erasmus MC-Sophia Children’s Hospital, Rotterdam, Netherlands, 2 UZ Brussels, Brussels, Belgium, 3 Nationwide Children’s Hospital, Columbus, OH, United States, 4 Hˆ opital Necker-Enfants Malades, Paris, France, 5 Abbott Laboratories, Abbott Park, IL, United States, 6 Connecticut Children’s Medical Center, Hartford, CT, United States Background: Adalimumab (ADA) has been shown to induce response and remission in moderate/severe pediatric Crohn’s disease (CD). We aimed to assess the effect of ADA treatment on quality of life (QOL) in pediatric patients (pts) with CD. Methods: IMAgINE 1 was a 52-week (wk), multi-center, doubleblind study assessing efficacy and safety of ADA in pts aged 6 17 years with moderate to severe CD (Pediatric CD Activity Index [PCDAI] >30) failing prior therapy, including infliximab. Following 4 wks of open-label induction, 188 pts were randomized 1:1 to standard dose (20 mg, bodyweight [BW] <40 kg, or 40 mg, BW 40 kg) or low dose (10 mg, BW <40 kg, or 20 mg, BW 40 kg) double-blind ADA every other wk. After wk 12, pts who experienced flare or nonresponse could switch to blinded weekly dosing and to standard dose open label therapy. To assess QOL, pts 10 years (N = 176) completed the IMPACT III, a 35-item questionnaire with scores ranging from 35 (poor) to 175 (best), at baseline and wks 12, 26, and 52. A change of 10.8 has been shown to indicate clinical improvement. Within group changes from baseline were assessed using paired t-tests. Changes from baseline were compared between dose groups using ANCOVA (adjusting for anti-TNF exposure, wk 4 response, and baseline IMPACT III score). LOCF was used for pts who discontinued or dose escalated.
Figure: Mean change from baseline in total IMPACT III score.
Results: At baseline, no significant differences were observed between dose groups in demographics, mean PCDAI scores, and prior anti-TNF exposure. The low dose group exhibited higher mean IMPACT III scores at baseline (117.7±15.5 vs. 111.6±18.7, P = 0.018). Both groups demonstrated significant improvements in mean IMPACT III scores at wks 12, 26, and 52 (figure). Improvements were observed in each domain, particularly in the bowel symptoms domain (4.7 4.8 change from baseline
S134 by week 12 in both dose groups). The effect was most pronounced in anti-TNF naïve pts and early responders. The standard dose group demonstrated slightly more improvement, but differences were not statistically significant. Conclusions: ADA treatment was associated with improved QOL in pediatric pts with CD by wk 12 and remained over the 52week study. P312 Acutec: differential diagnosis using computed tomography L. Plastaras1 *, S. Koch2 , L. Vuitton1 , E. Nedeva3 , V. di Martino4 , E. Delabrousse3 . 1 University Hospital of Besan¸con, Gastroenterology, Besan¸con, France, 2 University Hospital of Besan¸con, Gastroenterology, Besan¸con, France, 3 University Hospital of Besan¸con, Radiology, Besan¸con, France, 4 University Hospital of Besan¸con, Hepatology, Besan¸con, France Background: Etiological diagnosis of acute colitis (AC) is difficult, requiring bacteriologic, endoscopic, histopathological and outcome examinations. The aim of this work was to investigate the performance of Computed tomography (CT) to identify the cause of AC and study a new sign, the flat colon sign. Methods: This monocentric retrospective observational study included all consecutive patients admitted to the Gastroenterology department of the University Hospital of Besan¸ con from January 2006 to September 2010. All patients had AC with a clearly identified cause and all had had an abdominal CT scan. CT were retrospectively analyzed in a blinded test and result was then compaird with final etiological diagnosis. We studied the literature for all CT signs and we described a sign, not previously described in the literature: the flat colon sign. It was defined by a complete emptiness of the colonic lumen. Results: During the study period, 1452 patients were hospitalized for AC. Of them, 1247 were excluded because they didn’t undergo CT, or the cause of colitis remained uncertain. Study final population included 105 patients. CT identified 6 signs of inflammatory colitis (n = 43): comb sign, lymph nodes, abscesses, fibrofatty infiltration, involvement of the small bowel, and absence of flat colon sign. Multivariate analysis identified 3 signs: comb sign (OR = 15.16, [95% CI: 2.19 105.10], p = 0.006), small bowel involvement (OR = 6.35, [95% CI: 1.11 36.29], p = 0.037), and lymph nodes (OR = 16.66, [95% CI: 4.94 56.21], p < 0.001. Five signs were associated with infectious colitis (n = 35): continuous distribution, flat colon sign, fat stranding, and absence of comb sign and lymph nodes. Multivariate analysis identified 3 signs: flat colon sign (OR = 12.32 [95% CI: 1.68 90.15], p = 0.013), absence of fat stranding (OR = 3.85, [95% CI: 1.30 11.11], p = 0.014), and of comb sign (OR = 5.88 [95% CI: 1.18 33.33], p = 0.031). Five signs were associated with ischemic colitis (n = 21): fat stranding infiltration, and absence of lymph node, continuous distribution, comb sign, and small bowel involvement. Given the small number of patients in the ischemic colitis group, no multivariate analysis was performed. Conclusions: CT appears as a powerful tool to identify specific sign of each etiology of AC. CT is useful to distinguish inflammatory colitis from infectious colitis, particularly when considering the flat colon sign. A larger prospective study should be conducted to confirm these results.
Poster presentations P313 A composite serological panel predicts burden of inflammation in Crohn’s disease O. Ben-Bassat1 *, S. Lockton2 , F. Princen2 , J.M. Stempak3 , G. Van Assche1 , S. Singh2 , M.S. Silverberg1 . 1 Mount Sinai Hospital, Gastroenterology, Toronto, Canada, 2 Prometheus Labs, San Diego, United States, 3 Mount Sinai Hospital, Zane Cohen Centre for Digestive Diseases, Toronto, Canada Background: There remains a void in identifying biomarkers that can be used to measure the burden of inflammation in inflammatory bowel disease (IBD). Advances in therapeutic approaches suggest that mucosal healing is the ideal goal, however, currently endoscopic evaluation is the only accurate way to monitor this. CRP and fecal calprotectin have some utility but also several flaws. A multi-marker diagnostic panel containing inflammatory markers and serum antibodies was therefore examined to determine its potential utility as a measure of burden of inflammation. Methods: 174 patients with Crohn’s disease (CD) were evaluated with serological markers (ASCA-A and G, ANCA, pANCA, anti-OmpC, CBir1, A4-Fla2 and FlaX) and inflammatory markers (CRP, SAA, ICAM, VCAM, and VEGF) (Prometheus Laboratories, San Diego, CA). All had endoscopic assessment within 1 year of serum collection. Endoscopy reports were scored according to severity and disease extent and location. Analysis of variance (ANOVA) tests were applied to individual markers, and further location-specific marker patterns were analyzed to create a “marker signature” for each location and severity. An inflammatory index score was created by first entering each inflammatory marker to their respective reference range and, per subject, calculating the score as follows: (CRP + SAA)/2 + (ICAM + VCAM)/2 + VEGF. Results: The inflammatory index was significantly and positively associated with CD severity (p = 5.5×10 6 ). This index was independent of disease location (p = 0.335). 3 markers were significantly associated with increasing severity: CRP (p = 1.3×10 7 ), SAA (p = 8.8×10 5 ) & VEGF (p = 0.044). Similarly, five serological markers were associated with severity: ASCA-A (p = 0.021), ANCA (p = 0.041), CBir1 (p = 0.012), A4-Fla2 (p = 0.013) & FlaX (0.019). Colonic involvement was associated with higher VEGF (p = 0.0046) and CRP (p = 0.04), suggesting increased systemic inflammation. Disease location was also significantly associated with higher titres of ASCA-A (p = 0.001), ASCA-G (p = 0.004), Fla2 (p = 0.042) and FlaX (p = 0.021). There was a trend towards higher flagellin titres in left colonic CD. Conclusions: In this cohort, we demonstrated a significant correlation between CD disease severity, assessed endoscopically, with an inflammatory index score based on a panel of serum inflammatory markers. Furthermore, each disease location exhibited a unique serological marker pattern. This multi-marker diagnostic panel may be a useful instrument to assessing the burden of endoscopic disease severity in CD. P314 Accuracy of fecal calprotectin in the assessment of post-operative endoscopic recurrence in patients with Crohn’s disease e1 , G. Boschetti1 *, D. Moussata1 , A.-L. Charlois2 , B. Flouri´ S. Nancey1 . 1 Lyon-Sud Hospital, Gastroenterology, PierreB´ enite, France, 2 Lyon-Sud Hospital, Statistics, Pierre-B´ enite, France Background: Endoscopic post-operative recurrence is frequent in Crohn’s disease (CD) and is highly predictive of further clinical recurrence. Aims: i) to assess the performance of fecal calprotectin (fCal) to discriminate in CD patients who had undergone an ileo-colonic resection those who experienced an endoscopic recurrence from those who did not; ii) to determine the best threshold of fCal capable to distinguish CD patients with or without a post-operative endoscopic recurrence.