Brian Bressler

Keio University, Edo, Tōkyō, Japan

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Publications (134)

  • Article · May 2016
  • Article · May 2016
  • Article · May 2016
  • Astrid-Jane Greenup · Brian Bressler · Greg Rosenfeld
    [Show abstract] [Hide abstract] ABSTRACT: Background: Small bowel imaging in Crohn's disease (CD) is an important adjunct to endoscopy for the diagnosis, assessment of postoperative recurrence, and detection of complications. The best imaging modality for such indications though remains unclear. This systematic review aims to identify the imaging modality of choice considering the use of ultrasound (US), computed tomography enterography (CTE), and magnetic resonance enterography (MRE). Methods: Databases were systematically searched for studies pertaining to the performance of US, CTE, and MRE, as compared with a predefined reference standard in the assessment of small bowel CD. Results: Thirty-three studies, from a total of 1427 studies, were included in the final analysis. A comparable performance was demonstrated for MRE, CTE, and US for the diagnosis of small CD. Ultrasound was found to have the highest accuracy in the differentiation of inflammation and fibrosis. Postoperative recurrence detection was feasible with the use of MRE and US. All 3 modalities were shown to have a role in the detection of small bowel CD complications. The radiation exposure associated with CTE can be minimized by using lower radiation protocols. Conclusions: Ultrasound, CTE, and MRE all play an important role in the diagnosis and management of small bowel CD, with preference for a particular modality being influenced by specific indication, institution resources, and patient preference.
    Article · Apr 2016 · Inflammatory Bowel Diseases
  • [Show abstract] [Hide abstract] ABSTRACT: Background: Consensus on what constitutes a quality colonoscopy report for patients with inflammatory bowel disease (IBD) is lacking. We developed a template for quality colonoscopy reporting that can be used broadly by endoscopists. Methods: After a literature review of topics relevant to colonoscopy reporting, members of the Building Research in Inflammatory Bowel Disease Globally (BRIDGe) group and 2 external experts proposed candidate reporting elements. The RAND/University of California, Los Angeles appropriateness method was applied to rate the importance and feasibility of elements for inclusion in colonoscopy reports for patients with IBD. Panelists used the modified Delphi method to anonymously rate the importance and feasibility of candidate elements on a 1-to-9 scale (1-3: not important/feasible, 4-6: moderately important/feasible, 7-9: very important/feasible). Disagreement was assessed using a validated index. The panelists then met in person for discussion followed by a second round of voting. Elements rated a median of 7 or higher on importance after rerating were retained. Results: One hundred two reporting elements were proposed. A total of 48 elements were retained across the four themes of "disease background," "findings and interventions," "Crohn's disease with an ileocolonic anastomosis," and "pouchoscopy." Conclusions: A comprehensive list of recommended elements for quality IBD colonoscopy reporting stratified by clinical scenario has been described, using a rigorous and evidence-based approach. These elements can be incorporated into endoscopy reporting software platforms. Standardized endoscopy reporting may improve the quality of care in IBD.
    Article · Apr 2016 · Inflammatory Bowel Diseases
  • Brian Bressler · Martin A. Williamson · Fernando Camacho · [...] · A. Hillary Steinhart
    Article · Apr 2016 · Gastroenterology
  • James Lewis · Walter Reinisch · Brian Bressler · [...] · Tim Wyant
    Article · Apr 2016 · Gastroenterology
  • Gail Attara · Brian Bressler · Robert Bailey · [...] · Guy Aumais
    Article · Apr 2016 · Gastroenterology
  • Brian Bressler · Hal Gunn · Julie Jang · [...] · Jim Pankovich
    Article · Apr 2016 · Gastroenterology
  • George Ou · Brian Bressler · Cherry Galorport · [...] · Gregory Rosenfeld
    Article · Apr 2016 · Gastroenterology
  • Article · Apr 2016 · Gastroenterology
  • Neal Shahidi · Brian Bressler · Remo Panaccione
    [Show abstract] [Hide abstract] ABSTRACT: Vedolizumab, an α4β7-integrin antagonist, is the first gut-selective monoclonal antibody that has been approved for the treatment of moderate-to-severe ulcerative colitis and Crohn’s disease in many countries in the world. However, questions still remain regarding its appropriate use and placement in current treatment algorithms. Therefore, we sought out to evaluate the existing literature on the use of vedolizumab in inflammatory bowel disease. From inception to 21 June 2015 we searched MEDLINE for phase III randomized control trials assessing the utility of vedolizumab in inflammatory bowel disease, of which three were identified. The GEMINI trials demonstrate that vedolizumab is an effective and safe treatment for patients suffering from moderate-to-severe ulcerative colitis (GEMINI I) and Crohn’s disease (GEMINI II and III). However, further studies are needed comparing its efficacy directly with anti-tumor necrosis factor therapies to allow for further delineation of current treatment algorithms as well as ensuring its long-term safety profile.
    Article · Mar 2016 · Therapeutic Advances in Gastroenterology
  • Geert D’Haens · Brian Bressler · Silvio Danese · [...] · William Sandborn
    Article · Feb 2016
  • George Ou · Greg Rosenfeld · Brian Bressler
    Article · Jan 2016 · Canadian journal of surgery. Journal canadien de chirurgie
  • [Show abstract] [Hide abstract] 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.
    Article · Jan 2016 · Inflammatory Bowel Diseases
  • William J Sandborn · Jean-Frédéric Colombel · Subrata Ghosh · [...] · Allison Luo
    [Show abstract] [Hide abstract] 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.
    Article · Dec 2015 · Journal of Crohn s and Colitis
  • [Show abstract] [Hide abstract] 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.
    Article · Dec 2015 · Cochrane database of systematic reviews (Online)
  • Reena Khanna · Brian Bressler · Barrett G Levesque · [...] · Brian G Feagan
    [Show abstract] [Hide abstract] 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.
    Article · Sep 2015 · The Lancet
  • [Show abstract] [Hide abstract] ABSTRACT: 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 100 μg/g to 250 μg/g, inflammation is possible and further testing (eg, colonoscopy) is required to confirm inflammation; and when FC levels are >250 μg/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.
    Article · Jun 2015
  • [Show abstract] [Hide abstract] 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.
    Article · Jun 2015 · Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association