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William J Sandborn - One of the best experts on this subject based on the ideXlab platform.
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early Crohn Disease a proposed definition for use in Disease modification trials
Gut, 2010Co-Authors: Laurent Peyrinbiroulet, Edward V Loftus, Jeanfrederic Colombel, William J SandbornAbstract:Crohn Disease is a chronic condition characterised by intestinal inflammation and progressive bowel damage associated with impaired functioning. In rheumatoid arthritis, which shares some common aetiological pathways and treatments with Crohn Disease, treatment goals no longer include symptom control alone, but also alteration of the biological processes underlying synovial inflammation and progressive structural destruction, thereby preventing structural joint damage and functional decline.1 Analogous Disease-modifying treatment goals for Crohn Disease are currently being conceptualised and may include prevention of structural bowel damage (stricture, fistula, abscess) and impaired gastrointestinal physiology (ie, maintaining normal gastrointestinal physiology).2 3 In order to achieve Disease modification, an effective intervention must occur at the right time, that is, before the development of bowel damage and impaired functioning. While it has been said in this context ‘the earlier, the better’, there is no formal definition of early Crohn Disease.4 This article will review the rationale for defining early Crohn Disease and the rationale for specifically targeting early Crohn Disease from both immunopathological and clinical points of view, using rheumatoid arthritis (another chronic, progressive, destructive Disease), as an example. We will then propose a definition of early Crohn Disease and briefly discuss its potential application in future clinical trials. Studies from referral centres have demonstrated that the clinical features of Crohn Disease change over time with a decreasing frequency of inflammatory (non-stricturing non-penetrating) Disease behaviour and an increasing frequency of stricturing and/or penetrating Disease behaviour (Disease progression).5 6 Population-based studies have demonstrated that more than 50% of adult patients with Crohn Disease develop stricturing or penetrating intestinal complications within 20 years of diagnosis7 and similarly these complications occur in more than 50% of children after a median follow-up of 84 months.8 The development of these complications is associated with a need for surgical resection. …
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omega 3 free fatty acids for the maintenance of remission in Crohn Disease the epic randomized controlled trials
JAMA, 2008Co-Authors: Brian G Feagan, Ulrich Mittmann, S Barmeir, Geert R Dhaens, Marc Bradette, Albert Cohen, Chrystian Dallaire, Terry Ponich, William J Sandborn, John W D McdonaldAbstract:Context Maintenance therapy for Crohn Disease features the use of immunosuppressive drugs, which are associated with an increased risk of infection. Identification of safe and effective maintenance strategies is a priority. Objective To determine whether the oral administration of omega-3 free fatty acids is more effective than placebo for prevention of relapse of Crohn Disease. Design, Setting, and Patients Two randomized, double-blind, placebo-controlled studies (Epanova Program in Crohn's Study 1 [EPIC-1] and EPIC-2) conducted between January 2003 and February 2007 at 98 centers in Canada, Europe, Israel, and the United States. Data from 363 and 375 patients with quiescent Crohn Disease were evaluated in EPIC-1 and EPIC-2, respectively. Interventions Patients with a Crohn's Disease Activity Index (CDAI) score of less than 150 were randomly assigned to receive either 4 g/d of omega-3 free fatty acids or placebo for up to 58 weeks. No other treatments for Crohn Disease were permitted. Main Outcome Measure Clinical relapse, as defined by a CDAI score of 150 points or greater and an increase of more than 70 points from the baseline value, or initiation of treatment for active Crohn Disease. Results For EPIC-1, 188 patients were assigned to receive omega-3 free fatty acids and 186 patients to receive placebo. Corresponding numbers for EPIC-2 were 189 and 190 patients, respectively. The rate of relapse at 1 year in EPIC-1 was 31.6% in patients who received omega-3 free fatty acids and 35.7% in those who received placebo (hazard ratio, 0.82; 95% confidence interval, 0.51-1.19; P = .30). Corresponding values for EPIC-2 were 47.8% and 48.8% (hazard ratio, 0.90; 95% confidence interval, 0.67-1.21; P = .48). Serious adverse events were uncommon and mostly related to Crohn Disease. Conclusion In these trials, treatment with omega-3 free fatty acids was not effective for the prevention of relapse in Crohn Disease. Trial Registration clinicaltrials.gov Identifiers: EPIC-1: NCT00613197, EPIC-2: NCT00074542
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adalimumab induction therapy for Crohn Disease previously treated with infliximab a randomized trial
Annals of Internal Medicine, 2007Co-Authors: William J Sandborn, Geert R Dhaens, Jeanfrederic Colombel, Paul Rutgeerts, Robert Enns, Stephen B Hanauer, Remo Panaccione, Marie Rosenfeld, J D Kent, P F PollackAbstract:BACKGROUND Adalimumab, a fully human tumor necrosis factor (TNF) antagonist, is an effective treatment for patients with Crohn Disease who are naive to the chimeric TNF antagonist, infliximab. No anti-TNF agent has been evaluated prospectively in patients with Crohn Disease who had responded to another anti-TNF agent and then lost that response or were intolerant of the agent. OBJECTIVE To determine whether adalimumab induces remissions more frequently than placebo in adult patients with Crohn Disease who have symptoms despite infliximab therapy or who cannot take infliximab because of adverse events. DESIGN 4-week, randomized, double-blind, placebo-controlled trial (November 2004 to December 2005). SETTING 52 sites in the United States, Canada, and Europe. PATIENTS 325 adults 18 to 75 years of age who had a history of Crohn Disease for 4 months or more that was moderate to severe at baseline (Crohn's Disease Activity Index [CDAI] score, 220 to 450 points). INTERVENTION Patients were randomly assigned to receive induction doses of adalimumab, 160 mg and 80 mg, at weeks 0 and 2, respectively, or placebo at the same time points. MEASUREMENTS The primary end point was induction of remission at week 4. Decreases in CDAI score by 70 or more and 100 or more points (secondary end points) were also measured. RESULTS A total of 301 patients completed the trial. Twenty-one percent (34 of 159) of patients in the adalimumab group versus 7% (12 of 166) of those in the placebo group achieved remission at week 4 (P < 0.001). The absolute difference in clinical remission rates was 14.2 percentage points (95% CI, 6.7 to 21.6 percentage points). A 70-point response occurred at week 4 in 52% (82 of 159) of patients in the adalimumab group versus 34% (56 of 166) of patients in the placebo group (P = 0.001). The absolute difference in 70-point response rates was 17.8 percentage points (CI, 7.3 to 28.4 percentage points). Two of 159 patients in the adalimumab group and 4 of 166 patients in the placebo group discontinued treatment because of adverse events. No patients in the adalimumab group and 4 of 166 patients in the placebo group had a serious infection. LIMITATIONS The trial did not directly compare alternative active treatments and did not evaluate maintenance of response or long-term immunogenicity of adalimumab. CONCLUSION Adalimumab induces remissions more frequently than placebo in adult patients with Crohn Disease who cannot tolerate infliximab or have symptoms despite receiving infliximab therapy. For more information on adalimumab in Crohn Disease, click here. ClinicalTrials.gov registration number: NCT00105300.
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Crohn Disease mural attenuation and thickness at contrast enhanced ct enterography correlation with endoscopic and histologic findings of inflammation
Radiology, 2006Co-Authors: Kale D Bodily, William J Sandborn, Joel G Fletcher, Daniel C Johnson, Craig A Solem, Jeff L Fidler, John M Barlow, Michael R Bruesewitz, Cynthia H Mccollough, Edward V LoftusAbstract:Purpose: To determine retrospectively if quantitative measures of small-bowel mural attenuation and thickness at computed tomographic (CT) enterography correlate with endoscopic and histologic findings of small-bowel inflammation and to estimate the performance of these measures in predicting inflammatory Crohn Disease. Materials and Methods: The institutional review board approved this HIPAA-compliant retrospective study, which was conducted with patient informed consent. CT enterography data in 96 patients (31 male patients and 65 female patients) who underwent ileoscopy with or without biopsy were examined for CT signs of active Crohn Disease. The most highly enhancing segment of terminal ileum and a normal-appearing ileal loop were identified. After it was confirmed that semiautomated software could accurately measure mural attenuation and thickness, the selected terminal ileal and normal-appearing (control) ileal loops were examined (20 automated measurements at each location) to quantify mural atten...
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assessment of small bowel Crohn Disease noninvasive peroral ct enterography compared with other imaging methods and endoscopy feasibility study
Radiology, 2003Co-Authors: Peter B Wold, Joel G Fletcher, Daniel C Johnson, William J SandbornAbstract:A feasibility study was conducted to evaluate two biphasic computed tomographic (CT) enterography protocols, a noninvasive CT technique with water administered perorally and CT enteroclysis with methylcellulose administered through a nasojejunal tube, in 23 patients known or suspected to have Crohn Disease. Results were compared with the results of fluoroscopic small bowel examination and terminal ileoscopy for the detection of active Crohn Disease in the terminal ileum. Luminal distention did not differ significantly between the two CT protocols. Arterial phase imaging was noncontributory in 22 of 23 cases. The noninvasive peroral water CT enterography protocol had similar accuracy (12 of 15 cases, 80%) for enabling the detection of active Crohn Disease in comparison with CT enteroclysis with nasojejunal tube (seven of eight, 88%) and fluoroscopic small bowel examination (17 of 23, 74%). No fistulas were missed with use of either CT technique. The authors conclude that noninvasive peroral portal venous phase CT enterography with use of water is an accurate and feasible technique for detecting active small bowel inflammation in patients with Crohn Disease.
Daniel C Johnson - One of the best experts on this subject based on the ideXlab platform.
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Crohn Disease mural attenuation and thickness at contrast enhanced ct enterography correlation with endoscopic and histologic findings of inflammation
Radiology, 2006Co-Authors: Kale D Bodily, William J Sandborn, Joel G Fletcher, Daniel C Johnson, Craig A Solem, Jeff L Fidler, John M Barlow, Michael R Bruesewitz, Cynthia H Mccollough, Edward V LoftusAbstract:Purpose: To determine retrospectively if quantitative measures of small-bowel mural attenuation and thickness at computed tomographic (CT) enterography correlate with endoscopic and histologic findings of small-bowel inflammation and to estimate the performance of these measures in predicting inflammatory Crohn Disease. Materials and Methods: The institutional review board approved this HIPAA-compliant retrospective study, which was conducted with patient informed consent. CT enterography data in 96 patients (31 male patients and 65 female patients) who underwent ileoscopy with or without biopsy were examined for CT signs of active Crohn Disease. The most highly enhancing segment of terminal ileum and a normal-appearing ileal loop were identified. After it was confirmed that semiautomated software could accurately measure mural attenuation and thickness, the selected terminal ileal and normal-appearing (control) ileal loops were examined (20 automated measurements at each location) to quantify mural atten...
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assessment of small bowel Crohn Disease noninvasive peroral ct enterography compared with other imaging methods and endoscopy feasibility study
Radiology, 2003Co-Authors: Peter B Wold, Joel G Fletcher, Daniel C Johnson, William J SandbornAbstract:A feasibility study was conducted to evaluate two biphasic computed tomographic (CT) enterography protocols, a noninvasive CT technique with water administered perorally and CT enteroclysis with methylcellulose administered through a nasojejunal tube, in 23 patients known or suspected to have Crohn Disease. Results were compared with the results of fluoroscopic small bowel examination and terminal ileoscopy for the detection of active Crohn Disease in the terminal ileum. Luminal distention did not differ significantly between the two CT protocols. Arterial phase imaging was noncontributory in 22 of 23 cases. The noninvasive peroral water CT enterography protocol had similar accuracy (12 of 15 cases, 80%) for enabling the detection of active Crohn Disease in comparison with CT enteroclysis with nasojejunal tube (seven of eight, 88%) and fluoroscopic small bowel examination (17 of 23, 74%). No fistulas were missed with use of either CT technique. The authors conclude that noninvasive peroral portal venous phase CT enterography with use of water is an accurate and feasible technique for detecting active small bowel inflammation in patients with Crohn Disease.
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assessment of small bowel Crohn Disease noninvasive peroral ct enterography compared with other imaging methods and endoscopy feasibility study
Radiology, 2003Co-Authors: Peter B Wold, Joel G Fletcher, Daniel C Johnson, William J SandbornAbstract:A feasibility study was conducted to evaluate two biphasic computed tomographic (CT) enterography protocols, a noninvasive CT technique with water administered perorally and CT enteroclysis with methylcellulose administered through a nasojejunal tube, in 23 patients known or suspected to have Crohn Disease. Results were compared with the results of fluoroscopic small bowel examination and terminal ileoscopy for the detection of active Crohn Disease in the terminal ileum. Luminal distention did not differ significantly between the two CT protocols. Arterial phase imaging was noncontributory in 22 of 23 cases. The noninvasive peroral water CT enterography protocol had similar accuracy (12 of 15 cases, 80%) for enabling the detection of active Crohn Disease in comparison with CT enteroclysis with nasojejunal tube (seven of eight, 88%) and fluoroscopic small bowel examination (17 of 23, 74%). No fistulas were missed with use of either CT technique. The authors conclude that noninvasive peroral portal venous p...
Joel G Fletcher - One of the best experts on this subject based on the ideXlab platform.
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Crohn Disease mural attenuation and thickness at contrast enhanced ct enterography correlation with endoscopic and histologic findings of inflammation
Radiology, 2006Co-Authors: Kale D Bodily, William J Sandborn, Joel G Fletcher, Daniel C Johnson, Craig A Solem, Jeff L Fidler, John M Barlow, Michael R Bruesewitz, Cynthia H Mccollough, Edward V LoftusAbstract:Purpose: To determine retrospectively if quantitative measures of small-bowel mural attenuation and thickness at computed tomographic (CT) enterography correlate with endoscopic and histologic findings of small-bowel inflammation and to estimate the performance of these measures in predicting inflammatory Crohn Disease. Materials and Methods: The institutional review board approved this HIPAA-compliant retrospective study, which was conducted with patient informed consent. CT enterography data in 96 patients (31 male patients and 65 female patients) who underwent ileoscopy with or without biopsy were examined for CT signs of active Crohn Disease. The most highly enhancing segment of terminal ileum and a normal-appearing ileal loop were identified. After it was confirmed that semiautomated software could accurately measure mural attenuation and thickness, the selected terminal ileal and normal-appearing (control) ileal loops were examined (20 automated measurements at each location) to quantify mural atten...
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assessment of small bowel Crohn Disease noninvasive peroral ct enterography compared with other imaging methods and endoscopy feasibility study
Radiology, 2003Co-Authors: Peter B Wold, Joel G Fletcher, Daniel C Johnson, William J SandbornAbstract:A feasibility study was conducted to evaluate two biphasic computed tomographic (CT) enterography protocols, a noninvasive CT technique with water administered perorally and CT enteroclysis with methylcellulose administered through a nasojejunal tube, in 23 patients known or suspected to have Crohn Disease. Results were compared with the results of fluoroscopic small bowel examination and terminal ileoscopy for the detection of active Crohn Disease in the terminal ileum. Luminal distention did not differ significantly between the two CT protocols. Arterial phase imaging was noncontributory in 22 of 23 cases. The noninvasive peroral water CT enterography protocol had similar accuracy (12 of 15 cases, 80%) for enabling the detection of active Crohn Disease in comparison with CT enteroclysis with nasojejunal tube (seven of eight, 88%) and fluoroscopic small bowel examination (17 of 23, 74%). No fistulas were missed with use of either CT technique. The authors conclude that noninvasive peroral portal venous phase CT enterography with use of water is an accurate and feasible technique for detecting active small bowel inflammation in patients with Crohn Disease.
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assessment of small bowel Crohn Disease noninvasive peroral ct enterography compared with other imaging methods and endoscopy feasibility study
Radiology, 2003Co-Authors: Peter B Wold, Joel G Fletcher, Daniel C Johnson, William J SandbornAbstract:A feasibility study was conducted to evaluate two biphasic computed tomographic (CT) enterography protocols, a noninvasive CT technique with water administered perorally and CT enteroclysis with methylcellulose administered through a nasojejunal tube, in 23 patients known or suspected to have Crohn Disease. Results were compared with the results of fluoroscopic small bowel examination and terminal ileoscopy for the detection of active Crohn Disease in the terminal ileum. Luminal distention did not differ significantly between the two CT protocols. Arterial phase imaging was noncontributory in 22 of 23 cases. The noninvasive peroral water CT enterography protocol had similar accuracy (12 of 15 cases, 80%) for enabling the detection of active Crohn Disease in comparison with CT enteroclysis with nasojejunal tube (seven of eight, 88%) and fluoroscopic small bowel examination (17 of 23, 74%). No fistulas were missed with use of either CT technique. The authors conclude that noninvasive peroral portal venous p...
Peter B Wold - One of the best experts on this subject based on the ideXlab platform.
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assessment of small bowel Crohn Disease noninvasive peroral ct enterography compared with other imaging methods and endoscopy feasibility study
Radiology, 2003Co-Authors: Peter B Wold, Joel G Fletcher, Daniel C Johnson, William J SandbornAbstract:A feasibility study was conducted to evaluate two biphasic computed tomographic (CT) enterography protocols, a noninvasive CT technique with water administered perorally and CT enteroclysis with methylcellulose administered through a nasojejunal tube, in 23 patients known or suspected to have Crohn Disease. Results were compared with the results of fluoroscopic small bowel examination and terminal ileoscopy for the detection of active Crohn Disease in the terminal ileum. Luminal distention did not differ significantly between the two CT protocols. Arterial phase imaging was noncontributory in 22 of 23 cases. The noninvasive peroral water CT enterography protocol had similar accuracy (12 of 15 cases, 80%) for enabling the detection of active Crohn Disease in comparison with CT enteroclysis with nasojejunal tube (seven of eight, 88%) and fluoroscopic small bowel examination (17 of 23, 74%). No fistulas were missed with use of either CT technique. The authors conclude that noninvasive peroral portal venous phase CT enterography with use of water is an accurate and feasible technique for detecting active small bowel inflammation in patients with Crohn Disease.
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assessment of small bowel Crohn Disease noninvasive peroral ct enterography compared with other imaging methods and endoscopy feasibility study
Radiology, 2003Co-Authors: Peter B Wold, Joel G Fletcher, Daniel C Johnson, William J SandbornAbstract:A feasibility study was conducted to evaluate two biphasic computed tomographic (CT) enterography protocols, a noninvasive CT technique with water administered perorally and CT enteroclysis with methylcellulose administered through a nasojejunal tube, in 23 patients known or suspected to have Crohn Disease. Results were compared with the results of fluoroscopic small bowel examination and terminal ileoscopy for the detection of active Crohn Disease in the terminal ileum. Luminal distention did not differ significantly between the two CT protocols. Arterial phase imaging was noncontributory in 22 of 23 cases. The noninvasive peroral water CT enterography protocol had similar accuracy (12 of 15 cases, 80%) for enabling the detection of active Crohn Disease in comparison with CT enteroclysis with nasojejunal tube (seven of eight, 88%) and fluoroscopic small bowel examination (17 of 23, 74%). No fistulas were missed with use of either CT technique. The authors conclude that noninvasive peroral portal venous p...
Gregory Y Lauwers - One of the best experts on this subject based on the ideXlab platform.
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iatrogenic trichuris suis infection in a patient with Crohn Disease
Archives of Pathology & Laboratory Medicine, 2009Co-Authors: Richard L Kradin, Pavan Auluck, Joshua R Korzenik, Kamran Badizadegan, Gregory Y LauwersAbstract:Abstract We report a case of biopsy-proven iatrogenic infection by the pig whipworm Trichuris suis in a patient with Crohn Disease. The deliberate therapeutic ingestion of T suis ova has been adopt...
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iatrogenic trichuris suis infection in a patient with Crohn Disease
Archives of Pathology & Laboratory Medicine, 2006Co-Authors: Richard L Kradin, Pavan Auluck, Joshua R Korzenik, Kamran Badizadegan, Gregory Y LauwersAbstract:Abstract We report a case of biopsy-proven iatrogenic infection by the pig whipworm Trichuris suis in a patient with Crohn Disease. The deliberate therapeutic ingestion of T suis ova has been adopted as an experimental approach to the treatment of Crohn Disease in an effort to promote a switch from the T helper subtype 1 to T helper subtype 2 inflammatory phenotype in vivo. This report examines the morphology of the immature and adult T suis, the effects of this intervention on the immunophenotype of the bowel mucosa, and it also raises the possibility of persistent active infection in man.
