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P250 Elevated faecal calprotectin predicts disease progression in Crohn's disease
Clinical: Diagnosis and outcome P248 Endoscopic evaluation of colonic mucosa in ulcerative colitis patients in clinical remission O. Shchukina1 *, E. Kondrashina2 , O. Orlov3 , A. Vladimirova4 , A. Botina5 , E. Markova6 , A. Kharitidis7 . 1 North-West State Medical University, Chair of Gastroenterology and Dietology, Saint-Petersburg, Russian Federation, 2 North-West State University, Chair of Gastroenterology and Dietology, SaintPetersburg, Russian Federation, 3 City clinical hospital #3, Saint-Petersburg, Russian Federation, 4 Irkutsk Diagnostic Center, Irkutsk, Russian Federation, 5 Saint-Petersburg state medical university named after I.P. Pavlov, Saint-Petersburg, Russian Federation, 6 City clinical hospital #31, SaintPetersburg, Russian Federation, 7 City Clinical Hospital #31, City Centre of IBD, Saint-Petersburg, Russian Federation Background: Healing of colonic mucosa in ulcerative colitis (UC) is one of the main treatment goals; however definition of mucosal healing in UC has not been properly defined yet and criteria to assess endoscopic remission of UC within currently existing indices have not been duly validated. Our study aimed at validation of endoscopic signs of colonic mucosa in UC patients in clinical remission. Methods: 14 UC patients (pts) in clinical remission have been examined over a period of 2 16 months. Every colonoscopy was video-recorded and mucosa of 3 segments (ascendum, descendum and rectum) of large intestine was assessed by 3 independent endoscopists who were blinded to study results. Presence of the following features: erythema, disturbed or absence of vascular pattern, friability, bleeding, erosions, and mucosal granulations was registered. Endoscopists #1 and #2 used criteria of ECCO (2012) to assess friability, endoscopist #3 used his own criteria. Results: Erythema of mucosa in ascending colon were detected in 50%, 0% (p < 0.01), and 7% (p < 0.05) recordings by endoscopists #1, #2 and #3 respectively. Endoscopist #1 found erythema of mucosa in descendum in 43% pts, while both endoscopists #2 and #3 found this feature only in 7% pts (p < 0.05). Erythema of rectal mucosa was recorded by endoscopist #1 in 79%, whereas only in 7% (p < 0.01) of cases either by specialists # 2 and #3. Interestingly, significant differences between specialists were observed in assessment of friability. Endoscopist #3 found this feature in ascendum and rectum in 29% and 64% of pts respectively, whereas neither specialist #1 nor #2 did not found it at all (p < 0.05 and p < 0.001, respectively). Friability of mucosa in descendum was also noted with significantly different rate by specialist #3 comparing with either endoscopists #1 or #2: 50% and 7% (p < 0.05) respectively. There were no significant differences between specialists in assessment of the rest endoscopic criteria. Conclusions: Disturbed/absent vascular pattern, bleeding, erosions, mucosal granulations were found to be valid endoscopic findings in assessment of endoscopic remission in UC. Assessment of friability was considerably affected by personal subjectivity. Erythema of mucosa was concluded to be the least valid endoscopic criteria. Analysis of results from more number of pts is needed.
S109 P249 Endoscopic extension of inflammation progresses more frequently in ulcerative colitis compared to Crohn’s disease patients K. Katsanos1 *, V. Tsianos1 , T. Vasileiou1 , A. Tatsioni2 , D. Sigounas1 , I. Mitselos1 , D. Christodoulou1 , E. Tsianos1 , for the NW Greece IBD Study Group. 1 University of Ioannina, Ioannina, Greece, 2 Department of Family Medicine University of Ioanninaand Tufts-New England Medical Center EvidenceBased Practice Center, Institute for Clinical Research and Health Policy Studies, Boston, USA, Greece Background: The purpose of the study was to investigate the changes in endoscopic extension of inflammation during follow up IBD patients. Methods: Retrospective 30-year study (1982 2011) in a tertiary IBD referral center. All patients were on maintenance therapy and patients with at least two ileocolonoscopies with confirmation biopsies were included. Capsule endoscopy was not available in all patients and was not integrated in analysis. All medical records with corresponding lower gastrointestinal tract endoscopies from 631 (359 males) IBD patients (median age 47.9 years, 443 UC/ 135 CD / 53 indeterminate), were retrieved by two reviewers. Any change (extension) in endoscopic location of each patient was recorded separately. Results: In total 1736 endoscopies were reviewed (range 2 12 endoscopies per patient). Among 631 IBD patients a change of endoscopic extension of inflammation was observed in 59 (9.3%) of them. The median time of observing those changes in extension of inflammation was 6.8 years (range 4 10 years). Fifty-five patients were diagnosed with UC (93.2%) and 4 with CD (6.8%) while no changes were observed in patients with undetermined colitis. Among 55 UC patients, endoscopic inflammation was extended from proctitis to sigmoid colon (6 patients, 10.9%), from sigmoid colon to splenic flexure (26 patients, 47.3%) and from left-sided (sigmoid or up to the splenic flexure) colitis to pancolitis (23 patients, 41.8%). In CD patients endoscopic inflammation was extended from terminal ileitis to ileocolitis in all 4 patients. Conclusions: According to this observational study the endoscopy-proven extension of inflammation changes in 9.3% of IBD patients during long-term follow up and this seems to occur more frequently in UC compared to CD patients. This change in extent of IBD macroscopic inflammation needs further investigation also in the view of the new disease-modifying therapies. P250 Elevated faecal calprotectin predicts disease progression in Crohn’s disease N.A. Kennedy1 *, J. Chang2 , M.H. Guy2 , T. Smith2 , J.T. Loh2 , D. Haunschmidt2 , M. Muscat2 , F. Fascí Spurio2 , H.E. Drummond1 , K. Kingstone3 , C.L. Noble2 , A.G. Shand2 , J. Satsangi1 , I.D. Arnott2 , C.W. Lees2 . 1 Western General Hospital, Gastointestinal Unit, Molecular Medicine Centre, Edinburgh, United Kingdom, 2 Western General Hospital, Department of Gastroenterology, Edinburgh, United Kingdom, 3 Western General Hospital, Department of Clinical Biochemistry, Edinburgh, United Kingdom Background: Historical cohort studies have clearly demonstrated that over time the majority of patients with Crohn’s disease (CD) will progress from inflammatory (B1) to stricturing (B2) or fistulating (B3) disease. Emerging data suggest that more intensive treatment targeted towards mucosal healing will help to prevent disease progression. Faecal calprotectin (FC) is an established surrogate biomarker for endoscopic mucosal healing. It has yet to be established whether tailoring therapy to FC levels prevents disease progression. In the present study
S110 we aimed to determine whether FC levels in patients with established CD were predictive of disease progression. Methods: The Edinburgh Faecal Calprotectin Registry (EFCR) comprises data on 22,130 FC assays in 16,278 patients from 2005 2012. Detailed phenotypic information was obtained on patients with CD by retrospective casenote review. Data collected included demographics, disease location, disease behaviour over time, CD-related surgery, investigations, hospitalisations and drug therapy. Patients were included in the main analysis if they had at least 12 months’ follow-up since first FC. The a priori primary endpoint was a composite of progression in Montreal luminal behaviour, hospitalisation for flare and resectional surgery. Results: There were 801 CD patients identified with at least one FC, of which 650 had at least one year’s follow-up, representing 28,121 patient-months of follow-up. The median age was 28y (IQR 20 42) at diagnosis and 40y (28 53) at time of first FC. 211 patients reached the primary endpoint, of whom 57 had had progression of their Montreal behaviour from B1 to B2 or B3, or from B2 to B3. The median of the earliest FC was significantly higher in the group that reached the primary endpoint at 595 mg/g (IQR 210 1246) vs. 320 (80 992) in those that did not (p < 0.0001). Survival analysis (Figure 1) revealed significant differences in time to progression, hospitalisation or surgery with calprotectin 200 (p < 0.0001).
Poster presentations magnesium citrate have been used in bowel cleansing for more than 3 decades, head-to-head studies evaluating noninferiority have been limited. Methods: This phase 3, randomised, multicentre, assessorblinded study, conducted in the United States, investigated the efficacy and safety of day-before administration of a dual-action, low-volume bowel preparation containing sodium picosulfate and magnesium citrate (P/MC) vs 2 L polyethylene glycol solution and two 5-mg bisacodyl tablets (PEG + 2 bisacodyl tablets) in adult patients preparing for colonoscopy (NCT01073943, sponsored by Ferring Pharmaceuticals). A modified Aronchick scale was used to assess overall colon cleansing, and the Ottawa scale was used to evaluate colon cleansing of the ascending, mid, and recto-sigmoid segments. A noninferiority analysis was performed using the intent-to-treat population; if the 1-sided 97.5% confidence interval (CI) for the treatment difference between P/MC and PEG + 2 bisacodyl tablets was > 9%, noninferiority was demonstrated. Results: A total of 598 randomised patients self-administered either P/MC (n = 296) or PEG + 2 bisacodyl tablets (n = 302). P/MC was noninferior compared with PEG + 2 bisacodyl tablets in overall colon cleansing (CI: 2.9) and in cleansing of the ascending (CI: 8.8), mid (CI: 0.1), and recto-sigmoid (CI: 1.5) segments of the colon. More patients receiving P/MC had overall colon cleansing that was graded successful compared with PEG + 2 bisacodyl tablets (83.0% vs 79.7%). The proportion of patients who were successfully cleansed was similar for P/MC and PEG + 2 bisacodyl tablets in the ascending (81.3% vs 84.0%), mid (93.2% vs 88.7%), and recto-sigmoid (92.2% vs 89.0%) segments of the colon. The incidence of treatmentemergent adverse events (TEAEs) was similar between P/MC and PEG + 2 bisacodyl tablets (73.6% vs 79.8%). Commonly reported TEAEs attributed to P/MC or PEG + 2 bisacodyl tablets were nausea (3.0% vs 4.3%), vomiting (1.4% vs 2.0%), and headache (2.7% vs 1.7%). Conclusions: When combined with a split-dose regimen, daybefore dosing of P/MC provides alternatives for dosing to reduce the interval between the last dose of bowel preparation and colonoscopy start time with consideration for the schedule of the patient and clinic. P252 Efficacy and safety of a split-dose dual-action, low-volume bowel preparation for colonoscopy: the SEE CLEAR I study
Figure 1. Calprotectin and time to primary endpoint.
Conclusions: This large single-centre study presents compelling evidence that measurement of FC can be used to predict disease course, which creates the opportunity for physicians to intervene earlier and perhaps alter the disease course. P251 Efficacy and safety of day-before dosing of a dual-action, low-volume bowel preparation for colonoscopy: the SEE CLEAR II study P. Katz1 *, D. Rex2 , M. Epstein3 , J. Masure4 , R. Joseph5 . 1 Albert Einstein Healthcare Network, Philadelphia, United States, 2 Indiana University School of Medicine, Indianapolis, United States, 3 Digestive Disorders Associates, Annapolis, United States, 4 Ferring International Center SA, Saint-Prez, Switzerland, 5 Ferring Pharmaceuticals Inc, Parsippany, United States Background: The quality of bowel preparation is linked to the time interval between the last dose of preparation and colonoscopy start time. Thus, flexibility in dosing and scheduling is warranted. Although sodium picosulfate and
D. Rex1 *, P. Katz2 , G. Bertiger3 , J. Masure4 , R. Joseph5 . 1 Indiana University School of Medicine, Indianapolis, United States, 2 Albert Einstein Healthcare Network, Philadelphia, United States, 3 Hillmont GI, Flourtown, United States, 4 Ferring International Center SA, Saint-Prez, Switzerland, 5 Ferring Pharmaceuticals Inc, Parsippany, United States Background: Inadequate bowel cleansing has been shown to decrease detection of precancerous lesions. Split-dose administration of a bowel preparation has been demonstrated to maximise the efficacy of a colonoscopy. Although sodium picosulfate and magnesium citrate have been used in bowel cleansing for more than 3 decades, randomised, controlled studies utilising split dosing have been limited. Methods: This phase 3, randomised, multicentre, assessorblinded study, conducted in the United States, investigated the efficacy and safety of split-dose sodium picosulfate and magnesium citrate (P/MC) vs conventional dosing of 2 L polyethylene glycol solution and two 5-mg bisacodyl tablets (PEG + 2 bisacodyl tablets) in adult patients preparing for colonoscopy (NCT01073930, sponsored by Ferring Pharmaceuticals). A modified Aronchick scale was used to assess overall colon cleansing, and the Ottawa scale was used to evaluate cleansing of the colon segments. To assess noninferiority, a 97.5% 1-sided confidence interval (CI) was constructed for the success rate of P/MC minus PEG + 2
S109 P249 Endoscopic extension of inflammation progresses more frequently in ulcerative colitis compared to Crohn’s disease patients K. Katsanos1 *, V. Tsianos1 , T. Vasileiou1 , A. Tatsioni2 , D. Sigounas1 , I. Mitselos1 , D. Christodoulou1 , E. Tsianos1 , for the NW Greece IBD Study Group. 1 University of Ioannina, Ioannina, Greece, 2 Department of Family Medicine University of Ioanninaand Tufts-New England Medical Center EvidenceBased Practice Center, Institute for Clinical Research and Health Policy Studies, Boston, USA, Greece Background: The purpose of the study was to investigate the changes in endoscopic extension of inflammation during follow up IBD patients. Methods: Retrospective 30-year study (1982 2011) in a tertiary IBD referral center. All patients were on maintenance therapy and patients with at least two ileocolonoscopies with confirmation biopsies were included. Capsule endoscopy was not available in all patients and was not integrated in analysis. All medical records with corresponding lower gastrointestinal tract endoscopies from 631 (359 males) IBD patients (median age 47.9 years, 443 UC/ 135 CD / 53 indeterminate), were retrieved by two reviewers. Any change (extension) in endoscopic location of each patient was recorded separately. Results: In total 1736 endoscopies were reviewed (range 2 12 endoscopies per patient). Among 631 IBD patients a change of endoscopic extension of inflammation was observed in 59 (9.3%) of them. The median time of observing those changes in extension of inflammation was 6.8 years (range 4 10 years). Fifty-five patients were diagnosed with UC (93.2%) and 4 with CD (6.8%) while no changes were observed in patients with undetermined colitis. Among 55 UC patients, endoscopic inflammation was extended from proctitis to sigmoid colon (6 patients, 10.9%), from sigmoid colon to splenic flexure (26 patients, 47.3%) and from left-sided (sigmoid or up to the splenic flexure) colitis to pancolitis (23 patients, 41.8%). In CD patients endoscopic inflammation was extended from terminal ileitis to ileocolitis in all 4 patients. Conclusions: According to this observational study the endoscopy-proven extension of inflammation changes in 9.3% of IBD patients during long-term follow up and this seems to occur more frequently in UC compared to CD patients. This change in extent of IBD macroscopic inflammation needs further investigation also in the view of the new disease-modifying therapies. P250 Elevated faecal calprotectin predicts disease progression in Crohn’s disease N.A. Kennedy1 *, J. Chang2 , M.H. Guy2 , T. Smith2 , J.T. Loh2 , D. Haunschmidt2 , M. Muscat2 , F. Fascí Spurio2 , H.E. Drummond1 , K. Kingstone3 , C.L. Noble2 , A.G. Shand2 , J. Satsangi1 , I.D. Arnott2 , C.W. Lees2 . 1 Western General Hospital, Gastointestinal Unit, Molecular Medicine Centre, Edinburgh, United Kingdom, 2 Western General Hospital, Department of Gastroenterology, Edinburgh, United Kingdom, 3 Western General Hospital, Department of Clinical Biochemistry, Edinburgh, United Kingdom Background: Historical cohort studies have clearly demonstrated that over time the majority of patients with Crohn’s disease (CD) will progress from inflammatory (B1) to stricturing (B2) or fistulating (B3) disease. Emerging data suggest that more intensive treatment targeted towards mucosal healing will help to prevent disease progression. Faecal calprotectin (FC) is an established surrogate biomarker for endoscopic mucosal healing. It has yet to be established whether tailoring therapy to FC levels prevents disease progression. In the present study
S110 we aimed to determine whether FC levels in patients with established CD were predictive of disease progression. Methods: The Edinburgh Faecal Calprotectin Registry (EFCR) comprises data on 22,130 FC assays in 16,278 patients from 2005 2012. Detailed phenotypic information was obtained on patients with CD by retrospective casenote review. Data collected included demographics, disease location, disease behaviour over time, CD-related surgery, investigations, hospitalisations and drug therapy. Patients were included in the main analysis if they had at least 12 months’ follow-up since first FC. The a priori primary endpoint was a composite of progression in Montreal luminal behaviour, hospitalisation for flare and resectional surgery. Results: There were 801 CD patients identified with at least one FC, of which 650 had at least one year’s follow-up, representing 28,121 patient-months of follow-up. The median age was 28y (IQR 20 42) at diagnosis and 40y (28 53) at time of first FC. 211 patients reached the primary endpoint, of whom 57 had had progression of their Montreal behaviour from B1 to B2 or B3, or from B2 to B3. The median of the earliest FC was significantly higher in the group that reached the primary endpoint at 595 mg/g (IQR 210 1246) vs. 320 (80 992) in those that did not (p < 0.0001). Survival analysis (Figure 1) revealed significant differences in time to progression, hospitalisation or surgery with calprotectin 200 (p < 0.0001).
Poster presentations magnesium citrate have been used in bowel cleansing for more than 3 decades, head-to-head studies evaluating noninferiority have been limited. Methods: This phase 3, randomised, multicentre, assessorblinded study, conducted in the United States, investigated the efficacy and safety of day-before administration of a dual-action, low-volume bowel preparation containing sodium picosulfate and magnesium citrate (P/MC) vs 2 L polyethylene glycol solution and two 5-mg bisacodyl tablets (PEG + 2 bisacodyl tablets) in adult patients preparing for colonoscopy (NCT01073943, sponsored by Ferring Pharmaceuticals). A modified Aronchick scale was used to assess overall colon cleansing, and the Ottawa scale was used to evaluate colon cleansing of the ascending, mid, and recto-sigmoid segments. A noninferiority analysis was performed using the intent-to-treat population; if the 1-sided 97.5% confidence interval (CI) for the treatment difference between P/MC and PEG + 2 bisacodyl tablets was > 9%, noninferiority was demonstrated. Results: A total of 598 randomised patients self-administered either P/MC (n = 296) or PEG + 2 bisacodyl tablets (n = 302). P/MC was noninferior compared with PEG + 2 bisacodyl tablets in overall colon cleansing (CI: 2.9) and in cleansing of the ascending (CI: 8.8), mid (CI: 0.1), and recto-sigmoid (CI: 1.5) segments of the colon. More patients receiving P/MC had overall colon cleansing that was graded successful compared with PEG + 2 bisacodyl tablets (83.0% vs 79.7%). The proportion of patients who were successfully cleansed was similar for P/MC and PEG + 2 bisacodyl tablets in the ascending (81.3% vs 84.0%), mid (93.2% vs 88.7%), and recto-sigmoid (92.2% vs 89.0%) segments of the colon. The incidence of treatmentemergent adverse events (TEAEs) was similar between P/MC and PEG + 2 bisacodyl tablets (73.6% vs 79.8%). Commonly reported TEAEs attributed to P/MC or PEG + 2 bisacodyl tablets were nausea (3.0% vs 4.3%), vomiting (1.4% vs 2.0%), and headache (2.7% vs 1.7%). Conclusions: When combined with a split-dose regimen, daybefore dosing of P/MC provides alternatives for dosing to reduce the interval between the last dose of bowel preparation and colonoscopy start time with consideration for the schedule of the patient and clinic. P252 Efficacy and safety of a split-dose dual-action, low-volume bowel preparation for colonoscopy: the SEE CLEAR I study
Figure 1. Calprotectin and time to primary endpoint.
Conclusions: This large single-centre study presents compelling evidence that measurement of FC can be used to predict disease course, which creates the opportunity for physicians to intervene earlier and perhaps alter the disease course. P251 Efficacy and safety of day-before dosing of a dual-action, low-volume bowel preparation for colonoscopy: the SEE CLEAR II study P. Katz1 *, D. Rex2 , M. Epstein3 , J. Masure4 , R. Joseph5 . 1 Albert Einstein Healthcare Network, Philadelphia, United States, 2 Indiana University School of Medicine, Indianapolis, United States, 3 Digestive Disorders Associates, Annapolis, United States, 4 Ferring International Center SA, Saint-Prez, Switzerland, 5 Ferring Pharmaceuticals Inc, Parsippany, United States Background: The quality of bowel preparation is linked to the time interval between the last dose of preparation and colonoscopy start time. Thus, flexibility in dosing and scheduling is warranted. Although sodium picosulfate and
D. Rex1 *, P. Katz2 , G. Bertiger3 , J. Masure4 , R. Joseph5 . 1 Indiana University School of Medicine, Indianapolis, United States, 2 Albert Einstein Healthcare Network, Philadelphia, United States, 3 Hillmont GI, Flourtown, United States, 4 Ferring International Center SA, Saint-Prez, Switzerland, 5 Ferring Pharmaceuticals Inc, Parsippany, United States Background: Inadequate bowel cleansing has been shown to decrease detection of precancerous lesions. Split-dose administration of a bowel preparation has been demonstrated to maximise the efficacy of a colonoscopy. Although sodium picosulfate and magnesium citrate have been used in bowel cleansing for more than 3 decades, randomised, controlled studies utilising split dosing have been limited. Methods: This phase 3, randomised, multicentre, assessorblinded study, conducted in the United States, investigated the efficacy and safety of split-dose sodium picosulfate and magnesium citrate (P/MC) vs conventional dosing of 2 L polyethylene glycol solution and two 5-mg bisacodyl tablets (PEG + 2 bisacodyl tablets) in adult patients preparing for colonoscopy (NCT01073930, sponsored by Ferring Pharmaceuticals). A modified Aronchick scale was used to assess overall colon cleansing, and the Ottawa scale was used to evaluate cleansing of the colon segments. To assess noninferiority, a 97.5% 1-sided confidence interval (CI) was constructed for the success rate of P/MC minus PEG + 2