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What is the Best definition of Mucosal Healing in Crohn Disease?
AGA Abstracts
only abnormal (hypoglycosylated) MUC1. Results: A total of 62 CD post-op pts were evaluated. 18 had an endoscopic score of i0, with 3 pts (17%) showing high levels of MUC1 but none were the abnormal hypoglycosylated form. Of the 11 patients with i1 score, 4 (36%) expressed high levels of MUC1, but none were the abnormal hypoglycosylated MUC1 form. Of the 16 patients with an i2 score, 25% (4 pts) had elevated MUC1 with 1 pt demonstrating high levels of the hypoglycosylated form. 100% of pts with a score of i3 (7 pts) had elevated MUC1 with 57% (4 pts) expressing elevated hypoglycosylated form. Amongst post-op pts with the most severe epithelial damage (Rutgeerts i4), 60% of the 10 pts had elevated MUC1 levels and 2 of these pts had high expression of abnormal hypoglycosylated MUC1. (Table 1, Fig 1) Conclusions: High MUC1 expression is associated with severe post-operative endoscopic recurrence in the majority of CD pts with i3 and i4 scores. High levels of hypogylcosylated MUC1 was only seen in the setting of significant endoscopic recurrence (Rutgeerts i2, i3, i4 lesions). Given the ongoing application of human hypoglycosylated MUC1 vaccine trials to prevent polyps/colon cancer, further studies characterizing the biology of high hypoglycosylated MUC1 expression in CD inflammation are warranted to lay foundation for a vaccine trial to prevent CD post-operative recurrence. Table 1. MUC1 expression of patients with postoperative Crohn's disease based on endoscopic recurrence score
Endoscopic postoperative Rutgeerts ileal scores: i0 (normal), i1 (≤5 aphthous ulcers), i2 (>5 aphthous ulcers), i3 (diffuse aphthous ileitis), or i4 (diffuse inflammation with already large ulcers, nodules and/or narrowing). HMPV antibody stains all MUC1 (normal and abnormal); 4H5 antibody stains aberrant (hypoglycosylated) MUC1. 1126 WHAT IS THE BEST DEFINITION OF MUCOSAL HEALING IN CROHN DISEASE? Clara Yzet, Julien Loreau, Jean-philippe LeMouel, Franck Brazier, Eric Nguyen-Khan, Jean-Louis Dupas, Mathurin Fumery Background: Mucosal healing (MH) in Crohn disease (CD) has been associated with favorable outcome with long-term clinical remission and decreased rate of surgical resection. However, there is no consensus on the definition of MH in CD. We aimed to compare the risk of relapse and of intestinal resection in patients with CD according to different definitions of MH. Methods: We retrospectively studied patients with MH with biologics therapy between 2004 and 2015. The primary endpoint was the occurrence of a clinical relapse defined by the need of biologics optimization, initiation of corticosteroids, hospitalization or intestinal resection. MH was defined by the CDEIS score (Crohn's disease endoscopic index). Results: A total of 82 patients were included. Among them, 34% were men, the median age was 35.7 years (IQR, 28.7 - 44.1), and 64% were treated with infliximab. During a median follow-up of 3.15 years (0.6-5.8), 30 patients (36.6%) had clinical relapse and among them 6 underwent intestinal resection. The rate of relapse and rate of intestinal resection were respectively 27% (13/47) and 0% (0/47) in patients with CDEIS = 0 ; 56% (9/16) and 18% (3/16) in patients with CDEIS > 0 and ≤ 4; and 39% (9/23) and 13% (3/23) in patients with partial healing (defined as decrease of the CDEIS > 50%). Patients with CDEIS = 0 had a significant decrease rate of relapse as compared to patients with CDEIS > 0 and ≤ 4 (Relative Risk 0.49, 95%CI, 0.26 - 0.92). Patients with CDEIS = 0 had a significant decrease risk of intestinal resection as compared to CDEIS > 0 and ≤ 4 (p = 0.014) and to patients with decreased of CDEIS > 50% (p = 0.0097). Conclusions: The use of a strict definition of mucosal healing (CDEIS = 0) is associated with a lower risk of clinical relapse and intestinal resection in Crohn's disease.
1128 MAGNETIC RESONANCE INDEX OF ACTIVITY (MARIA) AND CLERMONT SCORE ARE TWO MRI INDICES WHICH ARE HIGHLY AND EQUALLY EFFECTIVE IN DETECTING MUCOSAL HEALING IN CROHN'S DISEASE Anthony Buisson, Bruno Pereira, Marion Goutte, Maud Reymond, Christophe Allimant, Gilles Bommelaer, Constance Hordonneau
1127 OVEREXPRESSION AND HYPOGLYCOSYLATION OF MUC1 IS ASSOCIATED WITH ENDOSCOPIC RECURRENCE OF POST-OPERATIVE CROHN'S DISEASE Jana G. Hashash, Pamela Beatty, Kristen Critelli, Matthew Regueiro, Douglas J. Hartman, Miguel D. Regueiro, David G. Binion, Kimberly Goldby-Reffner, Olivera J. Finn
Background Mucosal healing is hitherto the most popular therapeutic endpoint in Crohn's disease (CD) and is currently defined as no endoscopic ulcers. As repeated colonoscopies is highly burdensome for IBD patients, alternative monitoring tools have been developed such as magnetic resonance imaging (MRI), which is an accurate examination for assessing activity in CD. To date, magnetic resonance index of activity (MaRIA) and Clermont score are the two main MRI indices available in grading CD severity. In the present study, we aimed to compare the performances of MaRIA (1) and Clermont (2) score in assessing mucosal healing in CD. Methods In this prospective study, all the patients underwent consecutively magnetic resonance entero-colonography (MREC) including diffusionweighted sequences with no bowel cleansing and with no rectal enema [2], and colonoscopy (with CDEIS and SES-CD calculation) within 4 weeks (mean interval=17±11 days). Radiologists were blinded from endoscopic findings and endoscopists were blinded from radiologic findings. Results Overall, 44 CD patients were included. Baseline characteristics of the patients are given in Table 1. Considering the 194 segments (ileum=37, colorectal=159), Clermont score correlated with segmental CDEIS (0.48; p<0.001) and segmental SES-CD (0.44; p<0.001). MaRIA correlated also with segmental CDEIS (0.48; p<0.001) and segmental SES-CD (0.45; p<0.001). According to the established cut-off values i.e. MaRIA > 7 and Clermont score > 8.4, the sensitivity of each index was 0.53 and 0.56, and the specificity was 0.80 and 0.82, respectively. The sensitivity for detecting deep ulcerations was 0.90 and 0.91 for the MaRIA and Clermont indices, respectively, with a specificity of 0.79 and 0.80. Taking into account the 44 included patients, deep MRI remission predicted mucosal healing
Background: MUC1 is an epithelial cell mucin that contributes to mucosal homeostasis and plays a protective role against inflammation. In the setting of inflammation and cancer, MUC1 is overexpressed and hypoglycosylated (ie abnormal MUC1 form). Studies showed that overexpression and hypoglycosylation of MUC1 drive chronic inflammation and progression to colitis associated colon cancer in IBD mouse models, Intervention with a vaccine against abnormal hypoglycosylated MUC1 administered early in life ameliorated subsequent progression to IBD and cancer in mice that spontaneously develop IBD. Association of hypoglycosylated MUC1 expression with clinical course of human IBD is not defined. We sought to evaluate if overexpressed and hypoglycosylated MUC1 is associated with emergence of inflammation in the neo-terminal ileal pinch biopsies of pts with post-operative Crohn's disease (CD). We hypothesized that overexpression and hypoglycosylation of MUC1 is associated with more severe endoscopic postoperative CD recurrence (i2, i3, i4). Methods: Archived neo-terminal ileum biopsies from pts who had undergone curative ileocecal resection for isolated terminal ileal CD were included. All pts had endoscopic postoperative Rutgeerts ileal recurrence score recorded at time of colonoscopy (i0 to i4). Consecutive tissue sections were stained using 2 different anti-MUC1 antibodies; (1) HMPV recognizes all MUC1 (normal glycosylated and abnormal hypoglycosylated), while (2) 4H5 recognizes
AGA Abstracts
S-210
only abnormal (hypoglycosylated) MUC1. Results: A total of 62 CD post-op pts were evaluated. 18 had an endoscopic score of i0, with 3 pts (17%) showing high levels of MUC1 but none were the abnormal hypoglycosylated form. Of the 11 patients with i1 score, 4 (36%) expressed high levels of MUC1, but none were the abnormal hypoglycosylated MUC1 form. Of the 16 patients with an i2 score, 25% (4 pts) had elevated MUC1 with 1 pt demonstrating high levels of the hypoglycosylated form. 100% of pts with a score of i3 (7 pts) had elevated MUC1 with 57% (4 pts) expressing elevated hypoglycosylated form. Amongst post-op pts with the most severe epithelial damage (Rutgeerts i4), 60% of the 10 pts had elevated MUC1 levels and 2 of these pts had high expression of abnormal hypoglycosylated MUC1. (Table 1, Fig 1) Conclusions: High MUC1 expression is associated with severe post-operative endoscopic recurrence in the majority of CD pts with i3 and i4 scores. High levels of hypogylcosylated MUC1 was only seen in the setting of significant endoscopic recurrence (Rutgeerts i2, i3, i4 lesions). Given the ongoing application of human hypoglycosylated MUC1 vaccine trials to prevent polyps/colon cancer, further studies characterizing the biology of high hypoglycosylated MUC1 expression in CD inflammation are warranted to lay foundation for a vaccine trial to prevent CD post-operative recurrence. Table 1. MUC1 expression of patients with postoperative Crohn's disease based on endoscopic recurrence score
Endoscopic postoperative Rutgeerts ileal scores: i0 (normal), i1 (≤5 aphthous ulcers), i2 (>5 aphthous ulcers), i3 (diffuse aphthous ileitis), or i4 (diffuse inflammation with already large ulcers, nodules and/or narrowing). HMPV antibody stains all MUC1 (normal and abnormal); 4H5 antibody stains aberrant (hypoglycosylated) MUC1. 1126 WHAT IS THE BEST DEFINITION OF MUCOSAL HEALING IN CROHN DISEASE? Clara Yzet, Julien Loreau, Jean-philippe LeMouel, Franck Brazier, Eric Nguyen-Khan, Jean-Louis Dupas, Mathurin Fumery Background: Mucosal healing (MH) in Crohn disease (CD) has been associated with favorable outcome with long-term clinical remission and decreased rate of surgical resection. However, there is no consensus on the definition of MH in CD. We aimed to compare the risk of relapse and of intestinal resection in patients with CD according to different definitions of MH. Methods: We retrospectively studied patients with MH with biologics therapy between 2004 and 2015. The primary endpoint was the occurrence of a clinical relapse defined by the need of biologics optimization, initiation of corticosteroids, hospitalization or intestinal resection. MH was defined by the CDEIS score (Crohn's disease endoscopic index). Results: A total of 82 patients were included. Among them, 34% were men, the median age was 35.7 years (IQR, 28.7 - 44.1), and 64% were treated with infliximab. During a median follow-up of 3.15 years (0.6-5.8), 30 patients (36.6%) had clinical relapse and among them 6 underwent intestinal resection. The rate of relapse and rate of intestinal resection were respectively 27% (13/47) and 0% (0/47) in patients with CDEIS = 0 ; 56% (9/16) and 18% (3/16) in patients with CDEIS > 0 and ≤ 4; and 39% (9/23) and 13% (3/23) in patients with partial healing (defined as decrease of the CDEIS > 50%). Patients with CDEIS = 0 had a significant decrease rate of relapse as compared to patients with CDEIS > 0 and ≤ 4 (Relative Risk 0.49, 95%CI, 0.26 - 0.92). Patients with CDEIS = 0 had a significant decrease risk of intestinal resection as compared to CDEIS > 0 and ≤ 4 (p = 0.014) and to patients with decreased of CDEIS > 50% (p = 0.0097). Conclusions: The use of a strict definition of mucosal healing (CDEIS = 0) is associated with a lower risk of clinical relapse and intestinal resection in Crohn's disease.
Figure 1. Abnormal MUC1 expression in human Crohn's disease. Representative immunostaining of terminal ileal biopsies of patients with endoscopic score of i0, i2, and i4. HMPV antibody stains all MUC1 (normal and abnormal); 4H5 antibody stains aberrant (hypoglycosylated) MUC1. Images are with 20x objective.
1128 MAGNETIC RESONANCE INDEX OF ACTIVITY (MARIA) AND CLERMONT SCORE ARE TWO MRI INDICES WHICH ARE HIGHLY AND EQUALLY EFFECTIVE IN DETECTING MUCOSAL HEALING IN CROHN'S DISEASE Anthony Buisson, Bruno Pereira, Marion Goutte, Maud Reymond, Christophe Allimant, Gilles Bommelaer, Constance Hordonneau
1127 OVEREXPRESSION AND HYPOGLYCOSYLATION OF MUC1 IS ASSOCIATED WITH ENDOSCOPIC RECURRENCE OF POST-OPERATIVE CROHN'S DISEASE Jana G. Hashash, Pamela Beatty, Kristen Critelli, Matthew Regueiro, Douglas J. Hartman, Miguel D. Regueiro, David G. Binion, Kimberly Goldby-Reffner, Olivera J. Finn
Background Mucosal healing is hitherto the most popular therapeutic endpoint in Crohn's disease (CD) and is currently defined as no endoscopic ulcers. As repeated colonoscopies is highly burdensome for IBD patients, alternative monitoring tools have been developed such as magnetic resonance imaging (MRI), which is an accurate examination for assessing activity in CD. To date, magnetic resonance index of activity (MaRIA) and Clermont score are the two main MRI indices available in grading CD severity. In the present study, we aimed to compare the performances of MaRIA (1) and Clermont (2) score in assessing mucosal healing in CD. Methods In this prospective study, all the patients underwent consecutively magnetic resonance entero-colonography (MREC) including diffusionweighted sequences with no bowel cleansing and with no rectal enema [2], and colonoscopy (with CDEIS and SES-CD calculation) within 4 weeks (mean interval=17±11 days). Radiologists were blinded from endoscopic findings and endoscopists were blinded from radiologic findings. Results Overall, 44 CD patients were included. Baseline characteristics of the patients are given in Table 1. Considering the 194 segments (ileum=37, colorectal=159), Clermont score correlated with segmental CDEIS (0.48; p<0.001) and segmental SES-CD (0.44; p<0.001). MaRIA correlated also with segmental CDEIS (0.48; p<0.001) and segmental SES-CD (0.45; p<0.001). According to the established cut-off values i.e. MaRIA > 7 and Clermont score > 8.4, the sensitivity of each index was 0.53 and 0.56, and the specificity was 0.80 and 0.82, respectively. The sensitivity for detecting deep ulcerations was 0.90 and 0.91 for the MaRIA and Clermont indices, respectively, with a specificity of 0.79 and 0.80. Taking into account the 44 included patients, deep MRI remission predicted mucosal healing
Background: MUC1 is an epithelial cell mucin that contributes to mucosal homeostasis and plays a protective role against inflammation. In the setting of inflammation and cancer, MUC1 is overexpressed and hypoglycosylated (ie abnormal MUC1 form). Studies showed that overexpression and hypoglycosylation of MUC1 drive chronic inflammation and progression to colitis associated colon cancer in IBD mouse models, Intervention with a vaccine against abnormal hypoglycosylated MUC1 administered early in life ameliorated subsequent progression to IBD and cancer in mice that spontaneously develop IBD. Association of hypoglycosylated MUC1 expression with clinical course of human IBD is not defined. We sought to evaluate if overexpressed and hypoglycosylated MUC1 is associated with emergence of inflammation in the neo-terminal ileal pinch biopsies of pts with post-operative Crohn's disease (CD). We hypothesized that overexpression and hypoglycosylation of MUC1 is associated with more severe endoscopic postoperative CD recurrence (i2, i3, i4). Methods: Archived neo-terminal ileum biopsies from pts who had undergone curative ileocecal resection for isolated terminal ileal CD were included. All pts had endoscopic postoperative Rutgeerts ileal recurrence score recorded at time of colonoscopy (i0 to i4). Consecutive tissue sections were stained using 2 different anti-MUC1 antibodies; (1) HMPV recognizes all MUC1 (normal glycosylated and abnormal hypoglycosylated), while (2) 4H5 recognizes
AGA Abstracts
S-210