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Crohn Disease: HELP
Articles by Dr. Brian Feagan
Based on 134 articles published since 2010
(Why 134 articles?)
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Between 2010 and 2020, B. Feagan wrote the following 134 articles about Crohn Disease.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6
1 Editorial Editorial: treating strictures in inflammatory bowel disease-authors' reply. 2018

Rieder, Florian / Feagan, Brian G / Jairath, Vipul / Anonymous4790970. ·Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, Ohio. · Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio. · Robarts Clinical Trials Inc., University of Western Ontario, London, ON, Canada. · Department of Medicine, University of Western Ontario, London, ON, Canada. · Department of Epidemiology and Biostatistics, University of Western Ontario, London, ON, Canada. ·Aliment Pharmacol Ther · Pubmed #30488620.

ABSTRACT: -- No abstract --

2 Editorial Editorial: aminosalicylates in Crohn's disease-prevalence, risks, costs and time to reassess? Authors' reply. 2018

Jairath, V / Ma, C / Feagan, B. ·Division of Gastroenterology, Department Medicine, Schulich School of Medicine, Western University, London, ON, Canada. · Department of Epidemiology and Biostatistics, Western University, London, ON, Canada. · Robarts Clinical Trial, London, ON, Canada. · University of Calgary, Calgary, Canada. ·Aliment Pharmacol Ther · Pubmed #30284736.

ABSTRACT: -- No abstract --

3 Editorial Editorial: the impact of the placebo effect in Crohn's disease - author's reply. 2017

Jairath, V / Feagan, B G. ·Department Medicine, Western University, London, ON, Canada. · Department of Epidemiology and Biostatistics, Western University, London, ON, Canada. · Robarts Clinical Trials Inc., London, ON, Canada. ·Aliment Pharmacol Ther · Pubmed #28474832.

ABSTRACT: -- No abstract --

4 Review What is the role of C-reactive protein and fecal calprotectin in evaluating Crohn's disease activity? 2019

Ma, Christopher / Battat, Robert / Khanna, Reena / Parker, Claire E / Feagan, Brian G / Jairath, Vipul. ·Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada; Robarts Clinical Trials, Inc. London, Ontario, Canada. Electronic address: christopher.ma@ucalgary.ca. · Robarts Clinical Trials, Inc. London, Ontario, Canada; Division of Gastroenterology, University of California San Diego, La Jolla, CA, United States. Electronic address: rbattat@ucsd.edu. · Division of Gastroenterology, Western University, London, Ontario, Canada. Electronic address: rkhanna3@uwo.ca. · Robarts Clinical Trials, Inc. London, Ontario, Canada. Electronic address: claire.parker@robartsinc.com. · Robarts Clinical Trials, Inc. London, Ontario, Canada; Division of Gastroenterology, Western University, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada. Electronic address: brian.feagan@robartsinc.com. · Robarts Clinical Trials, Inc. London, Ontario, Canada; Division of Gastroenterology, Western University, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada. Electronic address: vjairath@uwo.ca. ·Best Pract Res Clin Gastroenterol · Pubmed #31327404.

ABSTRACT: Historically, the evaluation of patients with Crohn's disease (CD) has centered on use of subjective symptom-based assessment. However, patients with CD experience a broad spectrum of non-specific symptoms that may not directly correlate with objective measures of inflammation. Endoscopy has been the gold standard for evaluating the burden and severity of mucosal disease. However, use of ileocolonoscopy for disease monitoring in long-term follow-up is limited by considerations of cost, resource utilization, and invasiveness. As treatment goals in CD have shifted towards 'treat-to-target' paradigms that emphasize tight control of inflammation, it has become increasingly evident that sensitive, accurate, and reliable measures of disease activity are required. The use of non-invasive serum and fecal biomarkers such as C-reactive protein (CRP) and fecal calprotectin (FC) has been evaluated in patients with CD for categorizing disease activity, predicting treatment response, identifying patients at risk for disease relapse, and as a potential therapeutic target. In this review, we summarize the interpretation of CRP and FC in patients with CD within specific clinical contexts and according to assay performance characteristics.

5 Review IL12/23 or selective IL23 inhibition for the management of moderate-to-severe Crohn's disease? 2019

Ma, Christopher / Panaccione, Remo / Khanna, Reena / Feagan, Brian G / Jairath, Vipul. ·Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada; Robarts Clinical Trials, Inc. London, Ontario, Canada. Electronic address: christopher.ma@ucalgary.ca. · Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada. Electronic address: rpanacci@ucalgary.ca. · Division of Gastroenterology, Western University, London, Ontario, Canada. Electronic address: rkhanna3@uwo.ca. · Robarts Clinical Trials, Inc. London, Ontario, Canada; Division of Gastroenterology, Western University, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada. Electronic address: brian.feagan@robartsinc.com. · Robarts Clinical Trials, Inc. London, Ontario, Canada; Division of Gastroenterology, Western University, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada. Electronic address: vjairath@uwo.ca. ·Best Pract Res Clin Gastroenterol · Pubmed #31327402.

ABSTRACT: The interleukin (IL)-12 family of cytokines, including IL12 and IL 23, play an important role in driving aberrant Th1 and Th17 immune responses in patients with Crohn's disease (CD). Targeting this pathway has opened new avenues for therapeutic intervention. The approval of ustekinumab, a monoclonal antibody blocking the common p40 subunit of IL12 and IL23, marked an important evolution in medical management for CD: this novel class of biologic therapy demonstrated efficacy in both patients naïve to biologics as well as in patients experiencing inadequate response or loss of response to TNF antagonists. However, as our understanding of the IL12/23 pathway has evolved, specific targeting of IL23 through its unique p19 subunit has become a focus for novel therapeutic development. IL23p19 antagonists have been shown in head-to-head trials to have superior efficacy to ustekinumab for other immune-mediated conditions such as psoriasis. In CD, phase II trials of monoclonal antibodies targeting IL23, including risankizumab and brazikumab, have shown promising results, with multiple agents now entering phase II or phase III studies. In this review, we summarize the current evidence for both anti-IL12/23p40 and anti-IL23p19 monoclonal antibodies in CD.

6 Review Benefit-Risk Assessment of Vedolizumab in the Treatment of Crohn's Disease and Ulcerative Colitis. 2019

Battat, Robert / Ma, Christopher / Jairath, Vipul / Khanna, Reena / Feagan, Brian G. ·Division of Gastroenterology, University of California, 9500 Gilman Dr, San Diego, La Jolla, CA, 92093, USA. · Robarts Clinical Trials Inc., 100 Dundas St., Suite 200, London, ON, N6A 5B6, Canada. · Division of Gastroenterology and Hepatology, University of Calgary, 2500 University Drive NW, Calgary, AB, T2N 1N4, Canada. · Department of Medicine, Victoria Hospital, University of Western Ontario, Rm. E6-117, London, ON, N6A 5A5, Canada. · Department of Epidemiology and Biostatistics, University of Western Ontario, Kresge Building, Room K201, London, ON, N6A 5C1, Canada. · Robarts Clinical Trials Inc., 100 Dundas St., Suite 200, London, ON, N6A 5B6, Canada. brian.feagan@robartsinc.com. · Department of Medicine, Victoria Hospital, University of Western Ontario, Rm. E6-117, London, ON, N6A 5A5, Canada. brian.feagan@robartsinc.com. · Department of Epidemiology and Biostatistics, University of Western Ontario, Kresge Building, Room K201, London, ON, N6A 5C1, Canada. brian.feagan@robartsinc.com. ·Drug Saf · Pubmed #30830573.

ABSTRACT: Vedolizumab, a humanized monoclonal antibody to the α4β7 integrin, reduces lymphocyte trafficking to the intestine. This gut-selective mechanism of action offers a safer alternative to other biologics used to treat ulcerative colitis (UC) and Crohn's disease (CD). We reviewed efficacy and safety data from randomized controlled trials (RCTs), open-label extension (OLE) and observational studies, and pooled analyses of vedolizumab therapy. In UC, RCTs demonstrate that vedolizumab is effective for induction and maintenance of remission, regardless of prior tumor necrosis factor (TNF) antagonist exposure. In CD, vedolizumab is moderately effective as an induction therapy and demonstrates efficacy as a maintenance agent. Secondary analyses indicate that prolonged induction therapy may result in greater efficacy, particularly in TNF antagonist-exposed patients. Comparative efficacy studies and network meta-analyses show similar efficacy to other biologic therapies. OLE studies in UC and CD demonstrate the durability of maintenance efficacy and low serious adverse event (SAE) rates. In an integrated safety analysis of controlled data, there was no significant difference in adverse event, SAE, infection and serious infection rates between vedolizumab and placebo. No drug-specific safety signals were identified. Immunogenicity rates were low and no cases of progressive multifocal leukoencephalopathy directly attributable to vedolizumab are reported in the literature. Vedolizumab is effective for induction and maintenance of inflammatory bowel disease with low treatment-related risks. Given the high therapeutic index of this gut-specific agent, it can be used as either a first- or second-line biologic therapy for UC and CD.

7 Review Update on C-reactive protein and fecal calprotectin: are they accurate measures of disease activity in Crohn's disease? 2019

Ma, Christopher / Battat, Robert / Parker, Claire E / Khanna, Reena / Jairath, Vipul / Feagan, Brian Gordon. ·a Division of Gastroenterology and Hepatology , University of Calgary , Calgary , Alberta , Canada. · b Robarts Clinical Trials Inc ., London , Ontario , Canada. · c Division of Gastroenterology , University of California San Diego , La Jolla , CA , USA. · d Department of Medicine , Western University , London , Ontario , Canada. · e Department of Epidemiology and Biostatistics , Western University , London , Ontario , Canada. ·Expert Rev Gastroenterol Hepatol · Pubmed #30791776.

ABSTRACT: INTRODUCTION: 'Treat-to-target' paradigms in Crohn's disease (CD) directed at suppressing intestinal inflammation require accurate and reliable measures of disease activity. Although endoscopy has traditionally been considered a gold standard, cost, complexity, resource limitations, and invasiveness are important limitations. Hence, substantial interest exists for non-invasive serum and fecal biomarkers, namely C-reactive protein (CRP) and fecal calprotectin (FC), in the diagnosis, monitoring, and treatment of CD. Areas covered: We review the evidence for using serum CRP and FC in distinguishing patients with CD from those with irritable bowel syndrome, categorizing disease activity among patients with an established diagnosis of CD, predicting the likelihood of treatment response, identifying asymptomatic patients in medically or surgically induced remission who are at risk for disease relapse, and as treatment targets. Expert commentary: Accurate interpretation of CRP and FC is dependent on several factors including the clinical context, the performance characteristics of the assay, the specified test cut-offs, and the pre-test probability of disease. Emerging evidence indicates that CRP and FC are valuable adjuncts for the management of CD in specific circumstances described in this review.

8 Review Controversies in Inflammatory Bowel Disease: Exploring Clinical Dilemmas Using Cochrane Reviews. 2019

East, James E / Boyapati, Ray K / Torres, Joana / Parker, Claire E / MacDonald, John K / Chande, Nilesh / Feagan, Brian G. ·Translational Gastroenterology Unit and Oxford NIHR Biomedical Research Centre, Experimental Medicine Division, Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom. · Department of Gastroenterology, Monash Health, Melbourne, Victoria, Australia. · Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA. · Hospital Beatriz Ângelo, Gastroenterology Division, Loures, Portugal. · Robarts Clinical Trials Inc. London, Ontario, Canada. · Cochrane IBD Group, University of Western Ontario, London, Ontario, Canada. · Division of Gastroenterology, Department of Medicine, University of Western Ontario, London, Ontario, Canada. · Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada. ·Inflamm Bowel Dis · Pubmed #30789982.

ABSTRACT: A symposium organized by the Cochrane IBD Group and presented at the 2017 Digestive Disease Week annual meeting reviewed the recent literature on several controversial topics in inflammatory bowel disease (IBD) management including the efficacy of oral aminosalicylates for induction and maintenance of Crohn's disease (CD), the feasibility of drug withdrawal in patients with quiescent CD, and strategies for detecting colon cancer in patients with IBD. This article summarizes the data presented at that session.

9 Review Effects of Vedolizumab Therapy on Extraintestinal Manifestations in Inflammatory Bowel Disease. 2018

Fleisher, Mark / Marsal, Jan / Lee, Scott D / Frado, Laura E / Parian, Alyssa / Korelitz, Burton I / Feagan, Brian G. ·Borland-Groover Clinic, Jacksonville, FL, USA. · Lund University, Lund, Sweden. · University of Washington, Seattle, WA, USA. · Mount Sinai Hospital, New York, NY, USA. · Johns Hopkins Hospital, Baltimore, MD, USA. · Division of Gastroenterology, Department of Medicine, Lenox Hill Hospital, New York, NY, 10075, USA. · Robarts Clinical Trials, Robarts Research Institute, Western University, 100 Dundas Street, Suite 200, London, ON, N6A 5B6, Canada. Brian.feagan@robartsinc.com. ·Dig Dis Sci · Pubmed #29484571.

ABSTRACT: BACKGROUND: Approximately 15-20% of ulcerative colitis patients and 20-40% of those with Crohn's disease experience extraintestinal manifestations (EIMs) of their inflammatory bowel disease (IBD). Clinicians who treat IBD must manage EIMs affecting multiple organs that variably correlate with intestinal disease activity. Vedolizumab is a monoclonal antibody for the treatment of IBD with a gut-selective mechanism of action. AIMS: This report evaluates whether vedolizumab is an effective treatment of EIMs, given its gut-specific mechanism of action. METHODS: We report 8 case studies of patients with various EIMs, including pyoderma gangrenosum, peripheral arthralgia/arthritis, axial arthropathies, erythema nodosum, and uveitis, who received vedolizumab therapy. RESULTS: Vedolizumab therapy was effective for pyoderma gangrenosum in ulcerative colitis, uveitis, erythema nodosum, polyarticular arthropathy, and ankylosing spondylitis/sacroiliitis but did not provide sustained benefit for the treatment of pyoderma gangrenosum in a patient with Crohn's disease. CONCLUSIONS: These cases demonstrate the potential of vedolizumab as a treatment of EIMs in patients with IBD.

10 Review Novel Therapies and Treatment Strategies for Patients with Inflammatory Bowel Disease. 2018

Duijvestein, Marjolijn / Battat, Robert / Vande Casteele, Niels / D'Haens, Geert R / Sandborn, William J / Khanna, Reena / Jairath, Vipul / Feagan, Brian G. ·Robarts Clinical Trials, San Diego, CA, USA. · Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA. · Academic Medical Center, Amsterdam, Netherlands. · Robarts Clinical Trials, Amsterdam, Netherlands. · Robarts Clinical Trials, London, Canada. · Department of Medicine, University of Western Ontario, London, ON, Canada. · Robarts Clinical Trials, London, Canada. vipul.jairath@robartsinc.com. · Department of Medicine, University of Western Ontario, London, ON, Canada. vipul.jairath@robartsinc.com. · Department of Epidemiology and Biostatistics, University of Western Ontario, London, Canada. ·Curr Treat Options Gastroenterol · Pubmed #29411220.

ABSTRACT: PURPOSE OF REVIEW: This article reviews current treatment options and strategies and provides an update on the status of drug development programs of new therapeutic agents for inflammatory bowel diseases (IBD). RECENT FINDINGS: In the past two decades, tumor necrosis factor antagonist therapy has given clinicians better treatment options. However, not all patients respond to induction therapy with these agents, and of those initially responding, up to 40% ultimately lose response due to suboptimal drug exposure (e.g., caused by immunogenicity), side effects, or other poorly characterized mechanisms. Recently, additional therapies, such as vedolizumab, an integrin blocker that prevents T cell trafficking to the gut, and ustekinumab, an antibody blocking the common p40 subunit of interleukin (IL)-12 and 23, were introduced to the market. In addition, other agents including novel anti-trafficking therapies (e.g., anti-β7 and sphingosine-1-phosphate receptor modulators), antibodies against p19 (unique to IL-23), and small molecules including Janus kinase inhibitors are under investigation in phase II and III trials. Furthermore, the management of IBD has evolved from targeting control of symptoms to suppression of mucosal inflammation. This shift in thinking has been accompanied by the early use of highly effective therapy in poor prognosis patients, accelerated treatment escalation and utilization of a treat to target paradigm approach, and adoption of therapeutic drug monitoring. The treatment landscape for IBD is rapidly evolving with the recent approval of novel biologics as well as several other agents in late phase of clinical development. Moreover, we have started to use agents more intelligently with a focus on risk stratification and early use of highly effective therapy in high-risk patients, treat to target using patient-reported outcomes (PROs), biomarkers, endoscopy, and therapeutic drug monitoring.

11 Review The Expanding Therapeutic Armamentarium for Inflammatory Bowel Disease: How to Choose the Right Drug[s] for Our Patients? 2018

Hindryckx, Pieter / Vande Casteele, Niels / Novak, Gregor / Khanna, Reena / D'Haens, Geert / Sandborn, William J / Danese, Silvio / Jairath, Vipul / Feagan, Brian G. ·Robarts Clinical Trials, Inc., University of Western Ontario, London, ON, Canada. · Department of Gastroenterology, University of Ghent, Ghent, Belgium. · Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA. · Department of Gastroenterology, Ljubljana University Medical Centre, Ljubljana, Slovenia. · Department of Medicine, University of Western Ontario, London, ON, Canada. · Inflammatory Bowel Disease Centre, Academic Medical Centre, Amsterdam, The Netherlands. · Department of Biomedical Sciences, Humanitas University, Milan, Italy. · Department of Epidemiology and Biostatistics, University of Western Ontario, London, ON, Canada. ·J Crohns Colitis · Pubmed #28961959.

ABSTRACT: The therapeutic landscape for inflammatory bowel disease [IBD] is rapidly evolving. Two new biologic drugs, vedolizumab and ustekinumab, have recently entered the marketplace, the first biosimilars have been introduced, and several other agents are at an advanced stage of clinical development. In parallel, therapeutic goals have shifted from symptom control towards mucosal healing and prevention of bowel damage. In the coming years, gastroenterologists will be faced with unprecedented choices when selecting the best treatment for their patients with IBD. In this article, we review existing data on the mechanisms of action, efficacy, and safety of recently approved and late-stage pipeline therapies, and use this information to speculate on the positioning of these drugs, alone or in combination, in therapeutic algorithms for Crohn's disease and ulcerative colitis.

12 Review The Evolution of Treatment Paradigms in Crohn's Disease: Beyond Better Drugs. 2017

Khanna, Reena / Jairath, Vipul / Feagan, Brian G. ·Department of Medicine, University of Western Ontario, 100 Dundas Street, Suite 200, London, Ontario N6A 5B6, Canada. · Department of Medicine, University of Western Ontario, 100 Dundas Street, Suite 200, London, Ontario N6A 5B6, Canada; Department of Epidemiology & Biostatistics, University of Western Ontario, 100 Dundas Street, Suite 200, London, Ontario N6A 5B6, Canada. · Department of Medicine, University of Western Ontario, 100 Dundas Street, Suite 200, London, Ontario N6A 5B6, Canada; Department of Epidemiology & Biostatistics, University of Western Ontario, 100 Dundas Street, Suite 200, London, Ontario N6A 5B6, Canada. Electronic address: brian.feagan@robartsinc.com. ·Gastroenterol Clin North Am · Pubmed #28838421.

ABSTRACT: Despite advances in care, most patients with Crohn's disease (CD) develop complications, such as fistulas, or require surgery. Given the recent advances in drug therapy, an opportunity exists to optimize the management of this chronic disease through early use of effective therapies, clear definition of treatment targets, and application of the principles of personalized medicine. In this article, the authors discuss the evolution of treatment algorithms for CD to incorporate these strategies.

13 Review Histologic scoring indices for evaluation of disease activity in Crohn's disease. 2017

Novak, Gregor / Parker, Claire E / Pai, Rish K / MacDonald, John K / Feagan, Brian G / Sandborn, William J / D'Haens, Geert / Jairath, Vipul / Khanna, Reena. ·Department of Gastroenterology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands. ·Cochrane Database Syst Rev · Pubmed #28731502.

ABSTRACT: BACKGROUND: Histologic assessment of mucosal disease activity has been increasingly used in clinical trials of treatment for Crohn's disease. However, the operating properties of the currently existing histologic scoring indices remain unclear. OBJECTIVES: A systematic review was undertaken to evaluate the development and operating characteristics of available histologic disease activity indices in Crohn's disease. SEARCH METHODS: Electronic searches of MEDLINE, EMBASE, PubMed, and the Cochrane Library (CENTRAL) databases from inception to 20 July 2016 were supplemented by manual reviews of bibliographies and abstracts submitted to major gastroenterology meetings (Digestive Disease Week, United European Gastroenterology Week, European Crohn's and Colitis Organisation). SELECTION CRITERIA: Any study design (e.g. randomised controlled trial, cohort study, case series) that evaluated a histologic disease activity index in patients with Crohn's disease was considered for inclusion. Study participants included adult patients (> 16 years), diagnosed with Crohn's disease using conventional clinical, radiographic or endoscopic criteria. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed the titles and abstracts of the studies identified from the literature search. The full text of potentially relevant citations were reviewed for inclusion and the study investigators were contacted as needed for clarification. Any disagreements regarding study eligibility were resolved by discussion and consensus with a third author.Two authors independently extracted and recorded data using a standard form. The following data were recorded from each eligible study: number of patients enrolled; number of patients per treatment arm; patient characteristics: age and gender distribution; description of histologic disease activity index utilized; and outcomes such as content validity, construct validity, criterion validity, responsiveness, intra-rater reliability, inter-rater reliability, and feasibility. MAIN RESULTS: Sixteen reports of 14 studies describing 14 different numerical histological indices fulfilled the inclusion criteria.Inter-rater reliability was assessed in one study. For the Naini and Cortina Score, estimates of correlation were 'almost perfect', ranging from r = 0.94 to 0.96. The methodological quality of this study with respect to reliability was 'good'.With respect to validity, correlation estimates between various histological scoring systems and Crohn's disease activity as measured by objective markers of inflammation (including C-reactive protein, erythrocyte sedimentation rate, fecal calprotectin and fecal lactoferrin); endoscopic disease activity scores; clinical disease activity scores; and quality of life questionnaires were reported. Comparisons between histologic scoring indices and endoscopic scoring indices ranged from no correlation to 'substantial' (r = 0.779). The methodological quality of the studies that explored validity ranged form 'poor' to 'good'.Responsiveness data were available in seven studies. After subjects were administered a treatment of known efficacy, statistically significant change in the index score was demonstrated in five studies with respect to six indices. Two studies failed to indicate whether there was statistically significant change in the index score post-treatment. With regard to methodological quality, six of the studies were rated as 'poor' and one of the studies was rated as 'fair'.Feasibility was assessed by one study. The Naini and Cortina Score was shown to be simple to use and feasible for every given case. AUTHORS' CONCLUSIONS: Currently there is no fully validated histological scoring index for evaluation of Crohn's disease activity. Development of a validated histological scoring index for Crohn's disease is a clinical and research priority.

14 Review Alicaforsen for the treatment of inflammatory bowel disease. 2017

Jairath, Vipul / Khanna, Reena / Feagan, Brian G. ·a Robarts Clinical Trials Inc. , University of Western Ontario , London , Ontario , Canada. · b Department of Medicine, Division of Gastroenterology , Western University , London , Canada. · c Department of Epidemiology and Biostatistics , University of Western Ontario , London , Ontario , Canada. ·Expert Opin Investig Drugs · Pubmed #28670932.

ABSTRACT: INTRODUCTION: Intracellular adhesion molecule-1 (ICAM-1), is a transmembrane glycoprotein of the immunoglobulin family, constitutively expressed on vascular endothelial cells and upregulated in inflamed colonic tissue. Alicaforsen, a 20 base ICAM-1 anti-sense oligonucleotide and highly selective ICAM-1 inhibitor, down-regulates ICAM-1 mRNA. Areas covered: We review mechanism of action, pharmacokinetics, pre-clinical, clinical and safety data of alicaforsen for the treatment of ulcerative colitis (UC), pouchitis and Crohn's disease (CD). Expert opinion: After 6 weeks of treatment, topical alicaforsen was significantly more effective than placebo in inducing remission in patients with moderate-severe distal UC, with treatment effects lasting up to 30 weeks. No difference was observed in head-head comparison with mesalamine topical enema, although alicaforsen appeared to have more durable treatment effect. Clinical trials of an intravenous formulation in Crohn's disease showed no significant treatment effect compared to placebo. An open-label trial in alicaforsen for pouchitis demonstrated encouraging results, now being assessed in a multi-national phase 3 trial. No major safety signals have been observed in UC patients treated with alicaforsen enemas. The potential as a novel therapy for pouchitis has led to orphan designation for this indication by the FDA and European Medicines Agency.

15 Review Pharmacokinetic drug evaluation of budesonide in the treatment of Crohn's disease. 2017

Kwapisz, Lukasz / Jairath, Vipul / Khanna, Reena / Feagan, Brian. ·a Department of Medicine , Western University , London , Canada. · b Robarts Clinical Trials Inc. , Western University , London , Canada. · c Department of Epidemiology and , Western University , London , Canada. ·Expert Opin Drug Metab Toxicol · Pubmed #28612627.

ABSTRACT: INTRODUCTION: Crohn's disease (CD) is a chronic inflammatory disorder that commonly affects the terminal ileum and proximal colon. Although systemic corticosteroids such as prednisone and methylprednisolone are widely used for treatment of CD, these agents have a high incidence of adverse drug reactions due to off-target effects. Budesonide is a locally acting corticosteroid with enhanced formulation properties that offer a superior therapeutic index in comparison to conventional members of the class. Areas covered: This review focuses on budesonide for the treatment of CD. The pharmacological and pharmacokinetics of the drug are summarized, along with clinical efficacy and safety data. We also indicate the role of budesonide in therapeutic algorithms. Expert opinion: Budesonide has an important role as an induction therapy in patients with mild to moderately active CD of the ileum and proximal colon. The most distinctive advantage of budesonide over conventional corticosteroids is a substantially reduced risk of corticosteroid-related side effects.

16 Review Review article: moving towards common therapeutic goals in Crohn's disease and rheumatoid arthritis. 2017

Allen, P B / Olivera, P / Emery, P / Moulin, D / Jouzeau, J-Y / Netter, P / Danese, S / Feagan, B / Sandborn, W J / Peyrin-Biroulet, L. ·Division of Gastroenterology, Ulster Hospital, Belfast, UK. · Gastroenterology Section, Department of Internal Medicine, Centro de Educación Médica e Investigaciones Clínicas (CEMIC), Buenos Aires, Argentina. · Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds Teaching Hospitals NHS Trust, Leeds, UK. · UMR 7365 IMoPA CNRS-Université de Lorraine, Biopôle de l'Université de Lorraine, Campus Biologie-Santé, Vandœuvre-lès-Nancy Cedex, France. · Department of Gastroenterology, IBD Center, Istituto Clinico Humanitas, Humanitas University, Milan, Italy. · Western University, London, ON, Canada. · Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA. · Inserm U954 and Department of Hepato-Gastroenterology, University Hospital of Nancy, Lorraine University, Vandoeuvre-les-Nancy, France. ·Aliment Pharmacol Ther · Pubmed #28247573.

ABSTRACT: BACKGROUND: Crohn's disease (CD) and rheumatoid arthritis are chronic, progressive and disabling conditions that frequently lead to structural tissue damage. Based on strategies originally developed for rheumatoid arthritis, the treatment goal for CD has recently moved from exclusively controlling symptoms to both clinical remission and complete mucosal healing (deep remission), with the final aim of preventing bowel damage and disability. AIM: To review the similarities and differences in treatment goals between CD and rheumatoid arthritis. METHODS: This review examined manuscripts from 1982 to 2016 that discussed and/or proposed therapeutic goals with their supportive evidence in CD and rheumatoid arthritis. RESULTS: Proposed therapeutic strategies to improve outcomes in both rheumatoid arthritis and CD include: (i) evaluation of musculoskeletal or organ damage and disability, (ii) tight control, (iii) treat-to-target, (iv) early intervention and (v) disease modification. In contrast to rheumatoid arthritis, there is a paucity of disease-modification trials in CD. CONCLUSIONS: Novel therapeutic strategies in CD based on tight control of objective signs of inflammation are expected to change disease course and patients' lives by halting progression or, ideally, preventing the occurrence of bowel damage. Most of these strategies require validation in prospective studies, whereas several disease-modification trials have addressed these issues in rheumatoid arthritis over the last decade. The recent approval of new drugs in CD such as vedolizumab and ustekinumab should facilitate initiation of disease-modification trials in CD in the near future.

17 Review Systematic review with meta-analysis: placebo rates in induction and maintenance trials of Crohn's disease. 2017

Jairath, V / Zou, G / Parker, C E / MacDonald, J K / Mosli, M H / AlAmeel, T / Al Beshir, M / AlMadi, M / Al-Taweel, T / Atkinson, N S S / Biswas, S / Chapman, T P / Dulai, P S / Glaire, M A / Hoekman, D / Kherad, O / Koutsoumpas, A / Minas, E / Restellini, S / Samaan, M A / Khanna, R / Levesque, B G / D'Haens, G / Sandborn, W J / Feagan, B G. ·London, ON, Canada. · Oxford, UK. · Jeddah, Saudi Arabia. · Dammam, Saudi Arabia. · Riyadh, Saudi Arabia. · Jabriya, Kuwait. · La Jolla, CA, USA. · Amsterdam, The Netherlands. · Geneva, Switzerland. · London, UK. ·Aliment Pharmacol Ther · Pubmed #28164348.

ABSTRACT: BACKGROUND: Minimising placebo response is essential for drug development. AIM: To conduct a meta-analysis to determine placebo response and remission rates in trials and identify the factors affecting these rates. METHODS: MEDLINE, EMBASE and CENTRAL were searched from inception to April 2014 for placebo-controlled trials of pharmacological interventions for Crohn's disease. Placebo response and remission rates for induction and maintenance trials were pooled by random-effects and mixed-effects meta-regression models to evaluate effects of study-level characteristics on these rates. RESULTS: In 100 studies containing 67 induction and 40 maintenance phases and 7638 participants, pooled placebo remission and response rates for induction trials were 18% [95% confidence interval (CI) 16-21%] and 28% (95% CI 24-32%), respectively. Corresponding values for maintenance trials were 32% (95% CI 25-39%) and 26% (95% CI 19-35%), respectively. For remission, trials enrolling patients with more severe disease activity, longer disease duration and more study centres were associated with lower placebo rates, whereas more study visits and longer study duration was associated with higher placebo rates. For response, findings were opposite such that trials enrolling patients with less severe disease activity and longer study duration were associated with lower placebo rates. Placebo rates varied by drug class and route of administration, with the highest placebo response rates observed for biologics. CONCLUSIONS: Placebo rates vary according to whether trials are designed for induction or maintenance and the factors influencing them differ for the endpoints of remission and response. These findings have important implications for clinical trial design in Crohn's disease.

18 Review Evolving Concepts in Phases I and II Drug Development for Crohn's Disease. 2017

Jairath, Vipul / Levesque, Barrett G / Vande Casteele, Niels / Khanna, Reena / Mosli, Mahmoud / Hindryckx, Pieter / Travis, Simon / Duijvestein, Marjolijn / Rimola, Jordi / Panes, Julian / D'Haens, Geert / Sandborn, William J / Feagan, Brian G. ·Department of Medicine, University of Western Ontario, London, ON, Canada. · Robarts Clinical Trials Inc., Robarts Research Institute, University of Western Ontario, London, ON, Canada. · Nuffield Department of Experimental Medicine, University of Oxford, Oxford, UK. · Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA. · KU Leuven Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium. · Department of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia. · University Hospital of Ghent, Ghent, Belgium. · Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, The Netherlands. · Hospital Clinic of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain. · Department of Medicine, University of Western Ontario, London, ON, Canada brian.feagan@robartsinc.com. · Department of Epidemiology and Biostatistics, University of Western Ontario, London, ON, Canada. ·J Crohns Colitis · Pubmed #27487793.

ABSTRACT: The highest attrition rates during drug development programmes occur at the proof of concept stage. Given the large number of molecules under development for Crohn's disease, a need exists to improve the efficiency of early drug development by fast-tracking promising agents and terminating ineffective ones. Multiple opportunities are available to achieve these goals, including the use of more responsive outcome measures, and the incorporation of sophisticated pharmacokinetic modelling and/or highly specific pharmacodynamic markers into exposure-based dosing regimens and novel trial designs. In this article we review these strategies and propose an integrated paradigm of early drug development in Crohn's disease.

19 Review Central Endoscopy Reading in Inflammatory Bowel Diseases. 2016

Panés, Julián / Feagan, Brian G / Hussain, Fez / Levesque, Barrett G / Travis, Simon P. ·Department of Gastroenterology, Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain jpanes@clinic.cat. · Robarts Clinical Trials, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada. · Quintiles Immunology and Internal Medicine, Medical Strategy & Science, Rockville, MD, USA. · Robarts Clinical Trials, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA. · Translational Gastroenterology Unit, Oxford University Hospitals, Oxford, UK. ·J Crohns Colitis · Pubmed #27604978.

ABSTRACT: Endoscopic assessment of the presence and severity of endoscopic lesions has become an essential part of clinical trials in ulcerative colitis and Crohn's disease, for both patient eligibility and outcome measures. Variability in lesion interpretation between and within observers and the potential bias of local investigators in patient assessment have long been recognized. This variability can be reduced, although not completely removed, by independent evaluation of the examinations by experienced off-site (central) readers, properly trained in regard to lesion definition and identification, that should be removed from direct patient contact and blinded to any other clinical or study data. Adding endoscopic demonstration of active disease to eligibility criteria has the potential to reduce placebo response rates, whereas in outcome assessment it has the potential to provide a more precise estimation of the treatment effect, increasing the efficiency of the study. Central endoscopy reading is still at the beginning of its development, and the paradigms of central reading need refinement in terms of the number of readers, the process by which a final score is assigned, the selection and sequence of central readers, and the endoscopic indices of choice.

20 Review Interpreting Registrational Clinical Trials of Biological Therapies in Adults with Inflammatory Bowel Diseases. 2016

Ghosh, Subrata / Sandborn, William J / Colombel, Jean-Frederic / Feagan, Brian G / Panaccione, Remo / Hanauer, Stephen / Schreiber, Stefan / Peyrin-Biroulet, Laurent / Vermeire, Severine / Eichner, Samantha / Huang, Bidan / Robinson, Anne M / Pappalardo, Brandee. ·*Department of Medicine, University of Calgary, Calgary, Alberta, Canada; †Division of Gastroenterology, University of California San Diego, La Jolla, California; ‡Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York; §Robarts Clinical Trials, Robarts Research Institute, Department of Medicine, University of Western Ontario, London, Ontario, Canada; ‖Department of Medicine, Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; ¶Department of Medicine, University Hospital Schleswig-Holstein, University of Kiel, Kiel, Germany; **INSERM Unité 954, Department of Gastroenterology, University of Lorraine, Nancy, France; ††Department of Gastroenterology, University Hospital Leuven, Leuven, Belgium; and ‡‡AbbVie Inc., North Chicago, Illinois. ·Inflamm Bowel Dis · Pubmed #27585411.

ABSTRACT: BACKGROUND: The use of biologics to treat inflammatory bowel disease is supported by robust randomized controlled trials in both ulcerative colitis and Crohn's disease. Nonetheless, an understanding of the principles of clinical trial design is necessary to extrapolate study findings to clinical practice. METHODS: We conducted a review of inflammatory bowel disease registrational clinical trials of biologics to determine how differences in trial design potentially influence results and interpretation. RESULTS: Registrational trials of biological agents have used diverse patient populations, outcome measures, and designs, which makes comparisons of results among studies difficult. Key differences among trials include patient populations, choice of symptom-based measures or objective outcomes as endpoints, and overall trial design. Additional factors, including analytical methods, can also influence the interpretation of outcomes. CONCLUSIONS: The most robust evidence is derived from comparative effectiveness trials. In the absence of these, clinicians should be aware of the various methodological issues which could impact interpretation of efficacy and safety outcomes, including differences in patient population, study design, and analytic methodology.

21 Review Emerging Therapies for Inflammatory Bowel Diseases. 2016

Khanna, Reena / Feagan, Brian G. ·Department of Medicine, University of Western Ontario, London, Ont., Canada. ·Dig Dis · Pubmed #27548692.

ABSTRACT: BACKGROUND: The past decade has seen important advances in the management of chronic inflammatory bowel diseases (IBD), consisting of Crohn's disease (CD) and ulcerative colitis. The development of TNF antagonists, the recognition of interrupting lymphocyte trafficking as an effective treatment strategy, confirmation of the value of combination therapy, and the need, particularly in CD, for the treatment of high-risk patients early in the disease course are all fundamental concepts upon which the next generation of IBD treatment algorithms will be built. Emerging concepts that will continue to evolve and shape the field include an increased emphasis on personalized medicine (right drug, right dose, right time) and the development of new therapeutic classes. In this article, we review the clinical data and provide some insights into recent data regarding IBD therapies. KEY MESSAGES: In this article, we review the mechanism of action and data for novel therapies in IBD with particular focus on the evidence for agents targeting leukocyte trafficking, cytokine signaling, including interleukin-12/23 and the Janus kinase-signal transducers/activators of transcription pathway, and the emergence of antisense therapy for the treatment of IBD. CONCLUSIONS: Multiple new therapies are emerging for IBD; however, the potential positioning of these agents in treatment algorithms is difficult to predict in the absence of comparative effectiveness studies.

22 Review Endoscopic scoring indices for evaluation of disease activity in Crohn's disease. 2016

Khanna, Reena / Nelson, Sigrid A / Feagan, Brian G / D'Haens, Geert / Sandborn, William J / Zou, G Y / MacDonald, John K / Parker, Claire E / Jairath, Vipul / Levesque, Barrett G. ·Department of Medicine, University of Western Ontario, London, ON, Canada. ·Cochrane Database Syst Rev · Pubmed #27501379.

ABSTRACT: BACKGROUND: Endoscopic assessment of mucosal disease activity is widely used to determine eligibility and response to therapy in clinical trials of treatment for Crohn's disease. However, the operating properties of the currently available endoscopic indices remain unclear. OBJECTIVES: A systematic review was undertaken to evaluate the development and operating characteristics of the Crohn's Disease Endoscopic Index of Severity (CDEIS) and Simple Endoscopic Scale for Crohn's Disease (SES-CD). SEARCH METHODS: Electronic searches of the MEDLINE (1966 to December 2015), EMBASE (1980 to December 2015), and Cochrane CENTRAL Register of Controlled Trials (Issue 12, 2015) databases were supplemented by manual reviews of reference listings and conference proceedings (Digestive Disease Week, United European Gastroenterology Week, European Crohn's and Colitis Organization). SELECTION CRITERIA: Any study design (e.g. randomized controlled trials, cohort studies, case series) that evaluated either or both the CDEIS or SES-CD in patients with Crohn's disease was considered for inclusion. Eligible participants were adult patients (> 16 years), diagnosed with Crohn's disease using conventional clinical, radiographic, and endoscopic criteria. DATA COLLECTION AND ANALYSIS: Two authors (RK, JKM) independently reviewed the titles and abstracts of the studies identified from the literature search. The full texts of potentially relevant citations were reviewed for inclusion and the study investigators were contacted to clarify any unclear data. Any disagreements were resolved by discussion and consensus with a third author. A standardized form was used to assess eligibility of trials for inclusion in the study and for data extraction.Two authors independently extracted and recorded data (RK, SAN). The number of patients enrolled; number of patients per treatment arm; patient characteristics including age and gender distribution; endoscopic index; and outcomes such as intra-rater reliability, inter-rater reliability responsiveness, validity, feasibility, construct validity, and criterion validity were recorded for each trial. MAIN RESULTS: Forty-three reports of 30 studies fulfilled the inclusion criteria.For the SES-CD, inter-rater reliability was assessed in four studies. In the development study for the SES-CD (Daperno 2004), the overall ICC (0.9815, 95% CI 0.9705 to 0.9884) and the kappa for the regions is high; however the paired raters were in the same room which introduces the potential for bias.For the CDEIS, inter-rater reliability was assessed in six studies. Daperno 2014 reported that the ICC for the CDEIS was 0.985 (95% CI 0.939-1.000) for average measures of video score and was 0.835 (95% CI 0.540-0.995) for single measures of video score.With respect to validity, correlation between the CDEIS and clinical measures, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), was also reported. The estimates of correlation with CRP were r = 0.521 (Sipponen 2010b), r = 0.553 (Sipponen 2008a) and r = 0.608 (Sipponen 2008c). For the SES-CD, the corresponding values for correlation with CRP ranged from r = 0.46 (Jones 2008) to r = 0.68 (Green 2011).Responsiveness data for the CDEIS were available in nine studies. Seven studies demonstrated statistically significant decreases in the CDEIS score after administration of a treatment of known efficacy. Minimal responsiveness data were available for the SES-CD. Sipponen 2010a and Sipponen 2010b demonstrated statistically significant changes in the SES-CD score after subjects were administered a treatment of known efficacy.No studies were identified that explicitly evaluated the feasibility for either the SES-CD or the CDEIS. The SES-CD requires fewer calculations and may therefore be easier to use than the CDEIS. AUTHORS' CONCLUSIONS: Although they are used in clinical trials, the CDEIS and SES-CD remain incompletely validated. Future research is required to determine the operating properties and to define the optimal index.

23 Review The Next Wave of Biological Agents for the Treatment of IBD: Evidence from Cochrane Reviews. 2016

Khanna, Reena / Chande, Nilesh / Vermeire, Séverine / Sandborn, William J / Parker, Claire E / Feagan, Brian G. ·*Division of Gastroenterology, Department of Medicine, Western University, London, Ontario, Canada; †Robarts Clinical Trials, Inc., Robarts Research Institute, Western University, London, Ontario, Canada; ‡Division of Gastroenterology, Department of Internal Medicine, University Hospital Gasthuisberg, Leuven, Belgium; §Division of Gastroenterology, University of California San Diego, La Jolla, California; and ‖Departments of Medicine and Epidemiology and Statistics, Western University, London, Ontario, Canada. ·Inflamm Bowel Dis · Pubmed #27306074.

ABSTRACT: Multiple new biological treatments for Crohn's disease and ulcerative colitis are becoming available. Specifically, vedolizumab and ustekinumab are monoclonal antibodies that target molecular pathways relevant to disease pathogenesis. What can Cochrane reviews tell us about the efficacy, safety, and immunogenicity of these new agents? A Cochrane inflammatory bowel disease group symposium held at the 2015 Digestive Diseases Week annual meeting addressed these questions. This article reviews the data presented at that session.

24 Review Anti-Integrins in Ulcerative Colitis and Crohn's Disease: What Is Their Place? 2016

Khanna, Reena / Mosli, Mahmoud H / Feagan, Brian G. ·Department of Medicine, University of Western Ontario, London, Ont., Canada. ·Dig Dis · Pubmed #26982012.

ABSTRACT: BACKGROUND: Inflammatory bowel diseases (IBD) are a group of heterogeneous conditions, characterized by immune-mediated inflammation of the gastrointestinal tract. Traditionally, medical management of these disorders has been based on use of systemic immunosuppressives. The development of new drugs that selectively inhibit leukocyte trafficking to the gut has the potential to reduce inflammation and minimize systemic toxicities. KEY MESSAGES: In this article, we review the immunology of the gut and the mechanism of action these emerging therapies for IBD. Natalizumab, a monoclonal antibody to the α4 integrin, was approved for the treatment of multiple sclerosis and showed promise in Crohn's disease (CD), however it is encumbered by the risk of progressive multifocal leukoencephalopathy. Vedolizumab inhibits the α4β7 integrin to induce clinical remission in patients with both ulcerative colitis and CD. Long-term safety data on this agent is not yet available. We also review agents in the pipeline. Finally, we discuss the positioning of therapies and potential alterations to therapeutic algorithms as new medications emerge. CONCLUSIONS: New therapies are emerging for IBD; however, long-term data are pending. The positioning of these agents in algorithms will evolve.

25 Review New Applications for Traditional Drugs in Inflammatory Bowel Disease: What Do Cochrane Reviews Tell Us? 2015

Chande, Nilesh / Marshall, John K / Seow, Cynthia H / Sandborn, William J / Parker, Claire E / Nelson, Sigrid / Feagan, Brian G. ·*Division of Gastroenterology, Department of Medicine, Western University, London, Ontario, CA; †Division of Gastroenterology, McMaster University, Hamilton, Ontario, CA; ‡Division of Gastroenterology, Departments of Medicine and Community Health Sciences, University of Calgary, Alberta, CA; §Division of Gastroenterology, University of California San Diego, La Jolla, CA; ‖Robarts Clinical Trials, Inc, Robarts Research Institute, Western University, London, Ontario, CA; Departments of ¶Medicine, and **Epidemiology and Statistics, Western University, London, Ontario, CA. ·Inflamm Bowel Dis · Pubmed #26540276.

ABSTRACT: Although multiple innovative treatments of inflammatory bowel disease have become available, research continues to refine the value of existing drug therapies for Crohn's disease and ulcerative colitis. What can Cochrane reviews tell us about evolving applications for traditional agents in inflammatory bowel disease? A Cochrane Collaboration symposium held at the 2014 Digestive Diseases Week annual meeting addressed this question. This article reviews the data presented at that session.

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