Brian Bressler

University of British Columbia - Vancouver, Vancouver, British Columbia, Canada

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Publications (107)870.89 Total impact

  • No preview · Article · Feb 2016
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    George Ou · Greg Rosenfeld · Brian Bressler

    Preview · Article · Jan 2016 · Canadian journal of surgery. Journal canadien de chirurgie
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    ABSTRACT: Background: Inflammatory bowel disease (IBD) incidence is increasing among low-risk populations. This study examined a cohort of Canadian South Asian (SA) children with IBD to determine if their disease course differed from non-SA (NSA) children. Methods: Children of SA ethnicity diagnosed with IBD between 1997 and 2012 were identified and compared with NSA children. Data on duration and the type of presenting symptoms, disease phenotype, corticosteroid exposure (CS), exclusive enteral nutrition use, time to commencement of immunomodulator (IM), biologic therapy, and surgical intervention were extracted. Results: Overall, 160 SA children were identified and compared with 783 NSA patients (Crohn's disease [CD]: 44% versus 72%; ulcerative colitis [UC]: 43% versus 21%; IBD-Unclassified: 13% versus 7%; P < 0.001). SA patients were predominantly second-generation Canadians (92%) and had shorter symptom duration (2 versus 4 months; P < 0.001). SA CD patients were less likely to have a parent with IBD (1% versus 14%; P = 0.003). SA patients had more extensive colonic disease (CD: 55% versus 35%; P = 0.005; UC: 77% versus 58%; P = 0.006); SA CD patients presented with more complicated disease (B2/B3: 39% versus 27%; P = 0.006) and UC patients presented with more severe disease (49% versus 23%; P < 0.001). In SA CD patients, CS use was higher (70% versus 58%; P = 0.045), and IM and biologic therapy were commenced earlier (P = 0.027; P = 0.047). SA UC patients were more likely to need CS and IM (P = 0.024; P < 0.001). Conclusions: These data describe an ethnically unique clinical phenotype, where SA children have a higher proportion of UC, shorter symptom duration, more extensive colonic disease, and are more likely to require earlier escalation of therapy.
    No preview · Article · Jan 2016 · Inflammatory Bowel Diseases
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    ABSTRACT: Objective: Interferon-γ-inducible protein-10 (IP-10) mediates immune cell trafficking from the circulation to the inflamed colon and decreases gut epithelial cell survival. IP-10 expression is increased in patients with ulcerative colitis (UC). We report efficacy and safety results from a dose-ranging induction study of eldelumab, a fully human monoclonal antibody to IP-10, in moderately to severely active UC. Design: Two hundred and fifty-two (252) adults with UC (Mayo score ≥6 and endoscopic subscore ≥2) were randomised 1:1:1 to placebo or eldelumab 15 or 25 mg/kg administered intravenously on days 1 and 8 and every other week thereafter. The primary endpoint was clinical remission (Mayo score ≤2; no individual subscale score >1) at week 11. Key secondary endpoints included Mayo score clinical response and mucosal healing at week 11. Results: Neither eldelumab 15 nor 25 mg/kg resulted in significant increases versus placebo in the proportion of patients achieving week 11 clinical remission. Remission and response rates were 17.6% and 47.1% with eldelumab 25 mg/kg, 13.1% and 44.0% with eldelumab 15 mg/kg, and 9.6% and 31.3% with placebo. Clinical remission and response rates were higher in anti-tumour necrosis factor (TNF)-naïve patients treated with eldelumab compared with placebo. Eldelumab treatment was well tolerated and no immunogenicity was observed. Conclusions: The primary endpoint was not achieved with induction treatment with eldelumab 15 or 25 mg/kg in patients with UC. Trends towards clinical remission and response were observed in the overall population and were more pronounced in anti-TNF-naïve patients. Eldelumab safety signals were consistent with those reported previously.
    No preview · Article · Dec 2015 · Journal of Crohn s and Colitis
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    ABSTRACT: Background: Etrolizumab (rhuMAb beta7) is an anti-integrin that selectively targets the β7 subunits of the α4β7 and αEβ7 integrins, which are involved in the pathogenesis of ulcerative colitis. Objectives: The objectives of this review were to assess the efficacy and safety of etrolizumab for induction of remission in ulcerative colitis. Search methods: We searched PubMed, MEDLINE, EMBASE, and the Cochrane Library (CENTRAL) from inception to 12 March 2015. References and conference abstracts were searched to identify additional studies. Selection criteria: Randomized controlled trials (RCTs) trials in which etrolizumab was compared to placebo or another active comparator in patients with active ulcerative colitis were included. Data collection and analysis: Two authors independently screened studies for inclusion, assessed methodological quality and extracted data. We assessed methodological quality using the Cochrane risk of bias tool. The primary outcome was failure to induce clinical remission (as defined by the primary studies). Secondary outcomes included failure to induce clinical improvement (as defined by the primary studies), failure to induce endoscopic remission (as defined by the primary studies), adverse events, serious adverse events, withdrawal due to adverse events, and health-related quality of life (as defined by the primary studies). We assessed the overall quality of the evidence using the GRADE criteria. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for each dichotomous outcome. Main results: Two RCTs including 172 patients with moderate to severe UC who failed conventional therapy met the inclusion criteria. Both studies were rated as low risk of bias. We did not pool efficacy data from the two included studies due to differences in dose and route of administration. The small phase I study found no statistically significant differences between etrolizumab and placebo in the proportion of patients who failed to enter remission (RR 1.04, 95% CI 1.04 to 1.69; participants = 23) or respond at week 10 (RR 1.67, 95% CI 0.26 to 10.82; participants = 23). The phase II study reported on failure to enter clinical remission at weeks 6 and 10. In the etrolizumab group 91% (71/78) of patients failed to enter remission at week 6 compared to 95% (39/41) of placebo patients (RR 0.96, 95% CI 0.87 to 1.06). Subgroup analysis revealed no statistically significant differences by dose. At week 10, there was a statistically significant difference in clinical remission rates favouring etrolizumab over placebo. Of the patients who received etrolizumab, 85% (66/78) failed to enter remission at week 10 compared to 100% (41/41) patients in the placebo group (RR 0.86, 95% CI 0.77 to 0.95). A subgroup analysis by dose found a statistically significant difference in clinical remission rates favoring 100 mg etrolizumab over placebo (RR 0.81 CI 95% 0.68 to 0.96), but not 300 mg etrolizumab over placebo (RR 0.91, 95% CI 0.80 to 1.03). No significant heterogeneity was detected for this comparison (P = 0.28, I(2) = 13.5%). GRADE analyses indicated that the overall quality of evidence for the clinical remission outcomes was moderate due to sparse data. Both of the included studies reported on safety. The outcome adverse events was initially pooled, however this analysis was removed due to high heterogeneity (I(2) = 88%). The phase I study found no statistically significant difference between etrolizumab and placebo in the proportion of patients who had at least one adverse event. Ninety-five per cent (36/38) of etrolizumab patients had at least one adverse event compared to 100% (10/10) of placebo patients (RR 0.98, 95% CI 0.84 to 1.14). Common adverse events reported in the phase I study included exacerbation of UC, headache, fatigue, abdominal pain, dizziness, nasopharyngitis, nausea, arthralgia and urinary tract infection. There was a statistically significant difference between etrolizumab and placebo in the proportion of patients who had at least one adverse event. Fifty-six per cent (44/78) of etrolizumab patients had at least one adverse event compared to 79% of placebo patients (RR 0.71, 95% CI 0.55 to 0.91). A GRADE analysis indicates that the overall quality of the evidence for this outcome was moderate due to sparse data. Common adverse events reported in the phase II study included worsening UC, nasopharyngitis, nervous system disorders, headache and arthralgia . A pooled analysis of two studies indicates that there was no statistically significant difference in the proportion of patients who had a serious adverse event. Twelve per cent (14/116) of etrolizumab patients had a serious adverse event compared to 12% of placebo patients (6/49) (RR 0.92, 95% CI 0.36 to 2.34). A GRADE analysis indicated that the overall quality of the evidence for this outcome was low due to very sparse data (20 events). Common serious adverse events included worsening of UC, impaired wound healing and bacterial peritonitis. Authors' conclusions: Moderate quality evidence suggests that etrolizumab may be an effective induction therapy for some patients with moderate to severe ulcerative colitis who have failed conventional therapy. Due to small numbers of patients in dose subgroups the optimal dosage of etrolizumab is unclear. Due to sparse data we are uncertain regarding the risk of adverse events and serious adverse events. Further studies are needed to determine the efficacy and safety of etrolizumab in this patient population. There are five ongoing phase III etrolizumab trials and two ongoing open-label extension studies that will provide important new information on the efficacy, safety and optimal dose of this drug for the treatment of UC.
    No preview · Article · Dec 2015 · Cochrane database of systematic reviews (Online)
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    ABSTRACT: Conventional management of Crohn's disease features incremental use of therapies. However, early combined immunosuppression (ECI), with a TNF antagonist and antimetabolite might be a more effective strategy. We compared the efficacy of ECI with that of conventional management for treatment of Crohn's disease. In this open-label cluster randomised controlled trial (Randomised Evaluation of an Algorithm for Crohn's Treatment, REACT), we included community gastroenterology practices from Belgium and Canada that were willing to be assigned to either of the study groups, participate in all aspects of the study, and provide data on up to 60 patients with Crohn's disease. These practices were randomly assigned (1:1) to either ECI or conventional management. The computer-generated randomisation was minimised by country and practice size. Up to 60 consecutive adult patients were assessed within practices. Patients who were aged 18 years or older; documented to have Crohn's disease; able to speak or understand English, French, or Dutch; able to access a telephone; and able to provide written informed consent were followed up for 2 years. The primary outcome was the proportion of patients in corticosteroid-free remission (Harvey-Bradshaw Index score ≤4) at 12 months at the practice level. This trial is registered with, number NCT01030809. This study took place between March 15, 2010, and Oct 1, 2013. Of the 60 practices screened, 41 were randomly assigned to either ECI (n=22) or conventional management (n=19). Two practices (one in each group) discontinued because of insufficient resources. 921 (85%) of the 1084 patients at ECI practices and 806 (90%) of 898 patients at conventional management practices completed 12 months follow-up and were included in an intention-to-treat analysis. The 12 month practice-level remission rates were similar at ECI and conventional management practices (66·0% [SD 14·0] and 61·9% [16·9]; adjusted difference 2·5%, 95% CI -5·2% to 10·2%, p=0·5169). The 24 month patient-level composite rate of major adverse outcomes defined as occurrence of surgery, hospital admission, or serious disease-related complications was lower at ECI practices than at conventional management practices (27·7% and 35·1%, absolute difference [AD] 7·3%, hazard ratio [HR]: 0·73, 95% CI 0·62 to 0·86, p=0·0003). There were no differences in serious drug-related adverse events. Although ECI was not more effective than conventional management for controlling Crohn's disease symptoms, the risk of major adverse outcomes was lower. The latter finding should be considered hypothesis-generating for future trials. ECI was not associated with an increased risk of serious drug-related adverse events or mortality. AbbVie Pharmaceuticals. Copyright © 2015 Elsevier Ltd. All rights reserved.
    No preview · Article · Sep 2015 · The Lancet
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    ABSTRACT: Background: Objective monitoring of the severity of inflammation in patients with inflammatory bowel disease (IBD) is an essential part of disease management. However, repeat endoscopy to define extent and severity of inflammation is not practical. Fecal calprotectin (FC) is a biomarker that can be used as a surrogate test to distinguish inflammatory from noninflammatory gastrointestinal disease. Methods: A targeted search of the literature regarding FC, focusing primarily on the past three years, was conducted to develop practical clinical guidance on the current utility of FC in the routine management of IBD patients. Results : It is recommended that samples for FC testing be obtained from the first bowel excretion of the day. FC testing should be used as standard of care to accurately confirm inflammation and 'real-time' disease activity when a clinician suspects an IBD flare. Although FC is a reliable marker of inflammation, its role in routine monitoring in improving long-term outcomes has not yet been fully assessed. Based on available evidence, the authors suggest the following cut-off values and management strategies: when FC levels are 50 g/g to 100 g/g, quiescent disease is likely and therapy should be continued; when FC levels are 100 g/g to 250 g/g, inflammation is possible and further testing (eg, colonoscopy) is required to confirm inflammation; and when FC levels are 250 g/g, active inflammation is likely and strategies to control inflammation should be initiated (eg, optimizing current therapies or switching to an alternative therapy). Discussion: FC is a useful biomarker to accurately assess the degree of inflammation and should be incorporated into the management of patients with IBD.
    No preview · Article · Jun 2015
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    ABSTRACT: There is debate over whether patients with Crohn's disease who start anti-tumor necrosis factor (TNF) therapy after failed immunomodulator therapy should continue to receive concomitant immunomodulators. We conducted a meta-analysis of subgroups from randomized controlled trials (RCTs) of anti-TNF agents to compare the efficacy and safety of concomitant immunomodulator therapy vs anti-TNF monotherapy. We performed a systematic review of literature published from 1980 through 2008, and identified 11 RCTs of anti-TNF agents in patients with luminal or fistulizing Crohn's disease. We excluded RCTs of patients who were naïve to anti-TNF and immunomodulator therapy. The primary endpoints were clinical response at weeks 4-14 and 24-30, and remission at weeks 24-30. Secondary endpoints included infusion- or injection-site reactions and selected adverse events. A priori subgroup analyses were performed to evaluate fistula closure and the efficacy and safety of combination therapy with different anti-TNF agents. Overall, combination therapy was no more effective than monotherapy in inducing 6 months remission (odds ratio [OR], 1.02; 95% confidence interval [CI], 0.80-1.31), inducing a response (OR, 1.08; 95% CI 0.79-1.48), maintaining a response (OR, 1.53; 95% CI 0.67-3.49), or inducing partial (OR, 1.25; 95% CI, 0.84-1.88) or complete fistula closure (OR, 1.10; 95% CI, 0.68-1.78). In subgroup analyses of individual anti-TNF agents, combination therapy was not more effective than monotherapy in inducing 6-month remission in those treated with infliximab (OR, 1.73; 95% CI, 0.97-3.07), adalimumab (OR, 0.88; 95% CI, 0.58-1.35), or certolizumab (OR, 0.93; 95% CI, 0.65-1.34). Overall, combination therapy was not associated with an increase in adverse events, but inclusion of infliximab was associated with fewer injection site reactions (OR, 0.46; 95% CI, 0.26-0.79.) CONCLUSIONS: Based on a meta-analysis, continued use of immunomodulator therapy after starting anti-TNF therapy is no more effective than anti-TNF monotherapy in inducing or maintaining response or remission. RCTs are needed to adequately assess the efficacy of continued immunomodulator therapy after anti-TNF therapy is initiated. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Jun 2015 · Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association
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    ABSTRACT: We investigated the mechanism of action, safety, and efficacy of the Site-Specific Immunomodulator (SSI) QBECO, a novel immunotherapy for Crohn’s disease (CD). Using human monocytic THP-1 cells, we demonstrate that SSI QBECO (derived from the common colon bacteria E. coli) activates macrophages to an M1 phenotype (associated with enhanced capacity to eliminate bacteria and activate innate immune responses). We assessed SSI QBECO in a compassionate use protocol of ten adult patients with active CD. Patients with moderate to severe clinical symptoms receiving conventional CD treatments and/or complementary therapies were included, except patients receiving anti-TNF medications. SSI QBECO was self-administered subcutaneously every second day, for a minimum of 2.5 months and a maximum of 11 months. All 10 patients reported improvement of symptoms while on the SSI QBECO treatment. Seven patients reported full resolution of clinical symptoms during a course of SSI QBECO of at least three months. Three patients have experienced ongoing sustained clinical remission after discontinuing all medications, including SSI treatment. The longest case of clinical remission is still ongoing (>4 years). No serious severe adverse clinical events were reported. Collectively, we conclude that treatment with the immunoactive SSI QBECO was well tolerated and effective for treatment of Crohn’s disease in this case series.
    Full-text · Article · Jun 2015 · Gastroenterology Research and Practice
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    Brian Bressler · Theo Dingermann

    Full-text · Article · Jun 2015
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    ABSTRACT: Computed tomography (CT) scans are commonly used to diagnose acute diverticulitis, but there are overlapping features between diverticulitis and colorectal cancer (CRC) on imaging studies. Hence, colonoscopy is typically recommended after an episode of acute diverticulitis to rule out underlying malignancy. Currently, 64-slice multidetector CT scanners are capable of providing higher-resolution images and may be able to distinguish malignancy from diverticular inflammation. We aimed to determine the prevalence of CRC among patients with CT-diagnosed acute diverticulitis. We performed a retrospective study of patients with acute diverticulitis diagnosed on CT scan between December 2005 and December 2010 at St. Paul's Hospital, Vancouver, BC. Nonresidents were excluded. We reviewed CT scan reports that included the term "diverticulitis," reports of follow-up colonic evaluation within 1 year of diagnosis and pathology results. We queried the provincial cancer registry to ensure no cases of CRC were missed. A total of 293 patients had acute diverticulitis diagnosed on CT scan, but 8 were nonresidents and were excluded. Of the 285 included in the analysis, the mean age was 59.4 ± 15.1 years, and 167 (58.6%) were men. Among the 114 patients who underwent follow-up evaluation, malignancy was diagnosed in 4 (3.5%). The overall prevalence of malignancy among patients with CT-diagnosed diverticulitis was 1.4%. Routine endoscopic evaluation after an episode of diverticulitis diagnosed with high-resolution CT scan does not appear to be necessary. Selective approach in patients with protracted clinical course or those with mass lesion/obstruction on CT scan may be of benefit.
    Full-text · Article · Jun 2015 · Canadian journal of surgery. Journal canadien de chirurgie

  • No preview · Article · May 2015 · Gastrointestinal Endoscopy

  • No preview · Article · May 2015 · Gastrointestinal Endoscopy

  • No preview · Article · May 2015 · Gastrointestinal Endoscopy

  • No preview · Article · Apr 2015 · Gastroenterology

  • No preview · Article · Apr 2015 · Gastroenterology

  • No preview · Article · Apr 2015 · Gastroenterology
  • Brian Bressler

    No preview · Article · Mar 2015 · Annals of internal medicine
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    ABSTRACT: The medical management of ulcerative colitis (UC) has improved through the development of new therapies and novel approaches that optimize existing drugs. Previous Canadian consensus guidelines addressed the management of severe UC in the hospitalized patient. We now present consensus guidelines for the treatment of ambulatory patients with mild-to-severe active UC. A systematic literature search identified studies on the management of UC. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Statements were developed through an iterative online platform, then finalized and voted on by a working group of specialists. The participants concluded that the goal of therapy is complete remission defined as both symptomatic and endoscopic remission without corticosteroids. The consensus includes 34 statements focused on five main drug classes, 5-aminosalicylate (ASA), corticosteroids, immunosuppressants, anti-tumor necrosis factor-alpha (TNF) therapies, and other therapies. Oral and rectal 5-ASAs are recommended first-line therapy for mild-to-moderate UC, with corticosteroid therapy for those who fail to achieve remission. Patients with moderate-to-severe UC, should undergo a course of oral corticosteroids, with transition to 5-ASA, thiopurines, anti-TNF therapy (with or without thiopurines or methotrexate), or vedolizumab maintenance therapy in those who successfully achieve symptomatic remission. For patients with corticosteroid-resistant/dependent UC, anti-TNF therapies or vedolizumab are recommended. Timely assessments of response and remission are critical to ensuring optimal outcomes. Optimal management of UC requires careful patient assessment, evidence-based use of existing therapies, and thorough assessment to define treatment success. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Mar 2015 · Gastroenterology
  • Ashley Charlebois · Greg Rosenfeld · Brian Bressler
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    ABSTRACT: Abstract Diet may be a successful part of the treatment plan for improving outcome in patients with inflammatory bowel disease (IBD). This study aimed to systematically review all published clinical trials evaluating the effects of a regular diet on symptoms of IBD. Three medical databases were searched for clinical trials evaluating an intervention that involved dietary manipulation using a regular diet on adults with IBD whose symptoms were objectively measured before and after the intervention. The most common types of regular diet interventions that we observed in the literature fell into the following three categories: low residue/low fibre diets, exclusion diets, or other specific diets. Of all included studies, the few that were of higher quality and that observed a statistically significant improvement in symptoms in the diet group compared to the control group fell under the exclusion diet group or the other specific diet group. We were able to identify several high quality clinical trials evaluating dietary manipulations on symptoms of IBD. Exclusion diets and the low FODMAP diet are two areas identified in this review that show promise for having therapeutic benefits for patients with IBD.
    No preview · Article · Jan 2015 · Critical Reviews in Food Science and Nutrition

Publication Stats

1k Citations
870.89 Total Impact Points


  • 2007-2015
    • University of British Columbia - Vancouver
      • Division of Gastroenterology
      Vancouver, British Columbia, Canada
  • 2006-2015
    • St. Paul's Hospital
      Saskatoon, Saskatchewan, Canada
  • 2012
    • Keio University
      • Cancer Center
      Edo, Tōkyō, Japan
  • 2004-2007
    • University of Toronto
      • • Department of Medicine
      • • Division of Gastroenterology
      Toronto, Ontario, Canada