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Crohn Disease: HELP
Articles by Dr. Stephen Hanauer
Based on 72 articles published since 2008
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Between 2008 and 2019, S. Hanauer wrote the following 72 articles about Crohn Disease.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Guideline Management of Crohn's disease in adults. 2009

Lichtenstein, Gary R / Hanauer, Stephen B / Sandborn, William J / Anonymous3630620. ·Department of Medicine, Division of Gastroenterology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. gary.lichtenstein@uphs.upenn.edu ·Am J Gastroenterol · Pubmed #19174807.

ABSTRACT: Guidelines for clinical practice are intended to suggest preferable approaches to particular medical problems as established by interpretation and collation of scientifically valid research, derived from extensive review of published literature. When data that will withstand objective scrutiny are not available, a recommendation may be made based on a consensus of experts. Guidelines are intended to apply to the clinical situation for all physicians without regard to specialty. Guidelines are intended to be flexible, not necessarily indicating the only acceptable approach, and should be distinguished from standards of care that are inflexible and rarely violated. Given the wide range of choices in any health-care problem, the physician should select the course best suited to the individual patient and the clinical situation presented. These guidelines are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee. Expert opinion is solicited from the outset for the document. The quality of evidence upon which a specific recommendation is based is as follows: Grade A: Homogeneous evidence from multiple well-designed randomized (therapeutic) or cohort (descriptive) controlled trials, each involving a number of participants to be of sufficient statistical power. Grade B: Evidence from at least one large well-designed clinical trial with or without randomization, from cohort or case-control analytic studies, or well-designed meta-analysis. Grade C: Evidence based on clinical experience, descriptive studies, or reports of expert committees. The Committee reviews guidelines in depth, with participation from experienced clinicians and others in related fields. The final recommendations are based on the data available at the time of the production of the document and may be updated with pertinent scientific developments at a later time.

2 Editorial The Holy Grail, or only half way there? 2015

Ananthakrishnan, Ashwin N / Hanauer, Stephen B. ·Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: aananthakrishnan@mgh.harvard.edu. · Feinberg School of Medicine, Northwestern University, Chicago, Illinois. ·Gastroenterology · Pubmed #25451664.

ABSTRACT: -- No abstract --

3 Editorial Reassessing the risks and benefits of thiopurines in Crohn's disease. 2013

Kinnucan, Jami A / Hanauer, Stephen B. · ·Clin Gastroenterol Hepatol · Pubmed #23333707.

ABSTRACT: -- No abstract --

4 Editorial What to take from TREAT? 2012

Hanauer, Stephen B. · ·Am J Gastroenterol · Pubmed #22951879.

ABSTRACT: The TREAT Registry is an updated submission of the 5-year follow-up of Crohn's disease patients from community and academic centers in North America treated with or without infliximab. Over 6,000 patients were followed for risks of mortality and serious infections. Similar to data presented after nearly 2 years of follow-up, mortality was similar for infliximab- and other-treatment-only patients. Infliximab, corticosteroids and narcotics were associated with increased risks of serious infections. Data presented is similar from data reported for controlled trials and observational series in patients with inflammatory bowel disease and rheumatoid arthritis.

5 Editorial Mea culpa. 2008

Hanauer, Stephen B. · ·Nat Clin Pract Gastroenterol Hepatol · Pubmed #18670441.

ABSTRACT: -- No abstract --

6 Review Evolving Considerations for Thiopurine Therapy for Inflammatory Bowel Diseases-A Clinical Practice Update: Commentary. 2019

Hanauer, Stephen B / Sandborn, William J / Lichtenstein, Gary R. ·Digestive Health Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois. · Division of Gastroenterology, University of California, San Diego, La Jolla, California. · Division of Gastroenterology, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: grl@uphs.upenn.edu. ·Gastroenterology · Pubmed #30195449.

ABSTRACT: Thiopurines (azathioprine, mercaptopurine, thioguanine) and methotrexate are widely used in a variety of clinical management scenarios for ulcerative colitis and Crohn's disease. With the introduction of biologic therapies over the last 2 decades, controversies have emerged as to how these immunomodulators should be used in clinical practice, either alone as monotherapies or in combination with biologic therapies. Here, we provide a summary of evidence and our interpretations regarding how physicians can or should incorporate these agents into clinical practice. We have organized the review into sections regarding their utility as monotherapy or as combination therapy with biologics and safety considerations. Clinical pharmacologic considerations are important regarding both efficacy and safety.

7 Review Optimizing pharmacologic management of inflammatory bowel disease. 2017

Chang, Shannon / Hanauer, Stephen. ·a Division of Gastroenterology , New York University Langone Medical Center , New York , NY , USA. · b Division of Gastroenterology , Northwestern University Feinberg School of Medicine , Chicago , IL , USA. ·Expert Rev Clin Pharmacol · Pubmed #28475384.

ABSTRACT: INTRODUCTION: As our medical armamentarium for IBD continues to expand, it is essential that clinicians understand both optimizing and sequencing of individual and combination therapeutic approaches with available medications. Areas covered: This review summarizes dosing strategies and therapeutic drug monitoring for pharmacologic optimization in IBD. Aminosalicylates remain first-line therapies for mild-to-moderate UC but have limited evidence of efficacy in CD. Budesonide provides an alternative to aminosalicylates when targeted to appropriate sites in the distal small bowel and colon, as do conventional corticosteroids when applied rectally. Systemic steroids are highly efficacious but burdened by toxicity. Thiopurines or methotrexate can be utilized as steroid-sparing agents. Biologic agents targeting TNF remain important for steroid-sparing therapy in moderate-to-severe UC and CD. Newer biologics targeting lymphocyte trafficking and lymphocyte activation are also efficacious for moderate-to-severe IBD. Near future conventional drug options include oral agents such as tofacitinib and mongersen. Expert commentary: Positioning therapies according to the location, phenotypes, and severity, as well as the use of therapeutic and clinical targets, will improve outcomes and minimize toxicities and therapeutic futilities. Future IBD treatment should focus on personalized therapy plans based on genetic determinants, targeted mechanisms of action, and pharmacologic optimization.

8 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.

9 Review Aminosalicylates for induction of remission or response in Crohn's disease. 2016

Lim, Wee-Chian / Wang, Yongjun / MacDonald, John K / Hanauer, Stephen. ·Department of Gastroenterology and Hepatology, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore, Singapore, S 308433. ·Cochrane Database Syst Rev · Pubmed #27372735.

ABSTRACT: BACKGROUND: Randomized trials investigating the efficacy of aminosalicylates for the treatment of mildly to moderately active Crohn's disease have yielded conflicting results. A systematic review was conducted to critically examine current available data on the efficacy of sulfasalazine and mesalamine for inducing remission or clinical response in these patients. OBJECTIVES: To evaluate the efficacy of aminosalicylates compared to placebo, corticosteroids, and other aminosalicylates (alone or in combination with corticosteroids) for the treatment of mildly to moderately active Crohn's disease. SEARCH METHODS: We searched PubMed, EMBASE, MEDLINE and the Cochrane Central Library from inception to June 2015 to identify relevant studies. There were no language restrictions. We also searched reference lists from potentially relevant papers and review articles, as well as proceedings from annual meetings (1991-2015) of the American Gastroenterological Association and American College of Gastroenterology. SELECTION CRITERIA: Randomized controlled trials that evaluated the efficacy of sulfasalazine or mesalamine in the treatment of mildly to moderately active Crohn's disease compared to placebo, corticosteroids, and other aminosalicylates (alone or in combination with corticosteroids) were included. DATA COLLECTION AND ANALYSIS: Data extraction and assessment of methodological quality was independently performed by the investigators and any disagreement was resolved by discussion and consensus. We assessed methodological quality using the Cochrane risk of bias tool. The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. The primary outcome measure was a well defined clinical endpoint of induction of remission or response to treatment. Secondary outcomes included mean Crohn's disease activity index (CDAI) scores, adverse events, serious adverse events and withdrawal due to adverse events. For dichotomous outcomes we calculated the pooled risk ratio (RR) and corresponding 95% confidence interval (CI) using a random-effects model. For continuous outcomes we calculated the mean difference (MD) and 95% CI using a random-effects model. Sensitivity analyses based on a fixed-effect model and duration of therapy were conducted where appropriate. MAIN RESULTS: Twenty studies (2367 patients) were included. Two studies were judged to be at high risk of bias due to lack of blinding. Eight studies were judged to be at high risk of bias due to incomplete outcomes data (high drop-out rates) and potential selective reporting. The other 10 studies were judged to be at low risk of bias. A non-significant trend in favour of sulfasalazine over placebo for inducing remission was observed, with benefit confined mainly to patients with Crohn's colitis. Forty-five per cent (63/141) of sulfasalazine patients entered remission at 17-18 weeks compared to 29% (43/148) of placebo patients (RR 1.38, 95% CI 1.00 to 1.89, 2 studies). A GRADE analysis rated the overall quality of the evidence supporting this outcome as moderate due to sparse data (106 events). There was no difference between sulfasalazine and placebo in adverse event outcomes. Sulfasalazine was significantly less effective than corticosteroids and inferior to combination therapy with corticosteroids (RR 0.64, 95% CI 0.47 to 0.86, 1 study, 110 patients). Forty-three per cent (55/128) of sulfasalazine patients entered remission at 17 to 18 weeks compared to 60% (79/132) of corticosteroid patients (RR 0.68, 95% CI 0.51 to 0.91; 2 studies, 260 patients). A GRADE analysis rated the overall quality of the evidence supporting this outcome as moderate due to sparse data (134 events). Sulfasalazine patients experienced significantly fewer adverse events than corticosteroid patients (RR 0.43, 95% CI 0.22 to 0.82; 1 study, 159 patients). There was no difference between sulfasalazine and corticosteroids in serious adverse events or withdrawal due to adverse events. Olsalazine was less effective than placebo in a single trial (RR 0.36, 95% CI 0.18 to 0.71; 91 patients). Low dose mesalamine (1 to 2 g/day) was not superior to placebo for induction of remission. Twenty-three per cent (43/185) of low dose mesalamine patients entered remission at week 6 compared to 15% (18/117) of placebo patients (RR = 1.46, 95% CI 0.89 to 2.40; n = 302). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was low due to risk of bias (incomplete outcome data) and sparse data (61 events). There was no difference between low dose mesalamine and placebo in the proportion of patients who had adverse events (RR 1.33, 95% CI 0.91 to 1.96; 3 studies, 342 patients) or withdrew due to adverse events (RR 1.21, 95% CI 0.75 to 1.95; 3 studies, 342 patients). High dose controlled-release mesalamine (4 g/day) was not superior to placebo, inducing a clinically non significant reduction in CDAI (MD -19.8 points, 95% CI -46.2 to 6.7; 3 studies, 615 patients), and was also inferior to budesonide (RR 0.56, 95% CI 0.40 to 0.78; 1 study, 182 patients, GRADE = low). While high dose delayed-release mesalamine (3 to 4.5 g/day) was not superior to placebo for induction of remission (RR 2.02, 95% CI 0.75 to 5.45; 1 study, 38 patients, GRADE = very low), no significant difference in efficacy was found when compared to conventional corticosteroids (RR 1.04, 95% CI 0.79 to 1.36; 3 studies, 178 patients, GRADE = moderate) or budesonide (RR 0.89, 95% CI 0.76 to 1.05; 1 study, 307 patients, GRADE = moderate). However, these trials were limited by risk of bias (incomplete outcome data) and sparse data (small numbers of events). There was a lack of good quality clinical trials comparing sulfasalazine with other mesalamine formulations. Adverse events that were commonly reported included headache, nausea, vomiting, abdominal pain and diarrhea. AUTHORS' CONCLUSIONS: Sulfasalazine is only modestly effective with a trend towards benefit over placebo and is inferior to corticosteroids for the treatment of mildly to moderately active Crohn's disease. Olsalazine and low dose mesalamine (1 to 2 g/day) are not superior to placebo. High dose mesalamine (3.2 to 4 g/day) is not more effective than placebo for inducing response or remission. However, trials assessing the efficacy of high dose mesalamine (4 to 4.5 g/day) compared to budesonide yielded conflicting results and firm conclusions cannot be made. Future large randomized controlled trials are needed to provide definitive evidence on the efficacy of aminosalicylates in active Crohn's disease.

10 Review Bowel Ultrasonography in the Management of Crohn's Disease. A Review with Recommendations of an International Panel of Experts. 2016

Calabrese, Emma / Maaser, Christian / Zorzi, Francesca / Kannengiesser, Klaus / Hanauer, Stephen B / Bruining, David H / Iacucci, Marietta / Maconi, Giovanni / Novak, Kerri L / Panaccione, Remo / Strobel, Deike / Wilson, Stephanie R / Watanabe, Mamoru / Pallone, Francesco / Ghosh, Subrata. ·*Gastroenterology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; †Ambulanzzentrum Gastroenterologie am Klinikum Lüneburg, Lüneburg, Germany; ‡Klinik für Allgemeine Innere Medizin und Gastroenterologie, Lüneburg, Germany; §Digestive Disease Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois; ‖Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota; ¶Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Canada; **Department of Clinical Sciences, L. Sacco University Hospital, Milan, Italy; ††University Hospital Erlangen, Erlangen, Germany; and ‡‡Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University Hospital, Tokyo, Japan. ·Inflamm Bowel Dis · Pubmed #26958988.

ABSTRACT: BACKGROUND: Bowel ultrasonography (US) is considered a useful technique for assessing mural inflammation and complications in Crohn's disease (CD). The aim of this review is to appraise the evidence on the accuracy of bowel US for CD. In addition, we aim to provide recommendations for its optimal use. METHODS: Publications were identified by literature search from 1992 to 2014 and selected based on predefined criteria: 15 or more patients; bowel US for diagnosing CD, complications, postoperative recurrence, activity; adequate reference standards; prospective study design; data reported to allow calculation of sensitivity, specificity, agreement, or correlation values; articles published in English. RESULTS: The search yielded 655 articles, of which 63 were found to be eligible and retrieved as full-text articles for analysis. Bowel US showed 79.7% sensitivity and 96.7% specificity for the diagnosis of suspected CD, and 89% sensitivity and 94.3% specificity for initial assessment in established patients with CD. Bowel US identified ileal CD with 92.7% sensitivity, 88.2% specificity, and colon CD with 81.8% sensitivity, 95.3% specificity, with lower accuracy for detecting proximal lesions. The oral contrast agent improves the sensitivity and specificity in determining CD lesions and in assessing sites and extent. CONCLUSIONS: Bowel US is a tool for evaluation of CD lesions in terms of complications, postoperative recurrence, and monitoring response to medical therapy; it reliably detects postoperative recurrence and complications, as well as offers the possibility of monitoring disease progression.

11 Review Treat to target: a proposed new paradigm for the management of Crohn's disease. 2015

Bouguen, Guillaume / Levesque, Barrett G / Feagan, Brian G / Kavanaugh, Arthur / Peyrin-Biroulet, Laurent / Colombel, Jean-Frederic / Hanauer, Stephen B / Sandborn, William J. ·Division of Gastroenterology, University of California San Diego, La Jolla, California; Service des Maladie de l'Appareil Digestif et INSERM U991, Centre Hospitalier Universitaire Pontchaillou et Université de Rennes 1, Rennes, France. · Division of Gastroenterology, University of California San Diego, La Jolla, California. · Robarts Clinical Trials, University of Western Ontario, London, Ontario, Canada. · Division of Rheumatology, University of California San Diego, La Jolla, California. · INSERM U954 and Department of Hepato-Gastroenterology, University Hospital of Nancy, Vandoeuvre-les-Nancy, France. · Icahn School of Medicine at Mount Sanai, New York, New York. · University of Chicago, Chicago, Illinois. · Division of Gastroenterology, University of California San Diego, La Jolla, California. Electronic address: wsandborn@ucsd.edu. ·Clin Gastroenterol Hepatol · Pubmed #24036054.

ABSTRACT: The traditional management of Crohn's disease, which is based on progressive, step-wise treatment intensification with re-evaluation of response according to symptoms, does not improve long-term outcomes of Crohn's disease and places patients at risk for bowel damage. The introduction of novel therapies and the development of new approaches to treatment in rheumatoid arthritis led to better outcomes for patients. Prominent among these is a "treat to target" strategy that is based on regular assessment of disease activity by using objective clinical and biological outcome measures and the subsequent adjustment of treatments. This approach is complementary to the concept of early intervention in high-risk patients. This review evaluates current literature on this topic and proposes a definition for the concept of treating to targets for Crohn's disease.

12 Review Placebo response rate in clinical trials of fistulizing Crohn's disease: systematic review and meta-analysis. 2014

Ford, Alexander C / Luthra, Pavit / Hanauer, Stephen B / Travis, Simon P / Harris, M Scott / Reinisch, Walter. ·Leeds Gastroenterology Institute, St James's University Hospital, Leeds, United Kingdom; Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, United Kingdom. Electronic address: alexf12399@yahoo.com. · Leeds Gastroenterology Institute, St James's University Hospital, Leeds, United Kingdom. · Digestive Health Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois. · Translational Gastroenterology Unit, Oxford University Hospitals, Oxford, United Kingdom. · Georgetown University School of Medicine, Washington, District of Columbia. · Gastroenterology Division, McMaster University, Health Sciences Center, Hamilton, Ontario, Canada. ·Clin Gastroenterol Hepatol · Pubmed #25218669.

ABSTRACT: BACKGROUND & AIMS: It is important to determine the magnitude and identify modifiers of the rate of response to placebo in clinical trials of fistulizing Crohn's disease (CD), to understand disease progression, and to calculate sample size. We conducted a systematic review and meta-analysis of rates of response to placebo in trials of patients with fistulizing CD. METHODS: We searched MEDLINE, EMBASE, EMBASE CLASSIC, and the Cochrane central register of controlled trials for randomized controlled trials (RCTs) comparing pharmacologic agents with placebo in adults with fistulizing CD. We identified studies that reported complete fistula closure, partial closure, or response. Data were extracted as intention-to-treat analyses and pooled by using a random-effects model. Proportions of patients who received placebo and had complete or partial fistula(e) closure were calculated, with 95% confidence intervals (CIs). The effects of trial characteristics on the magnitude of response to placebo were examined. RESULTS: Thirteen RCTs were eligible for our analysis; these included 579 patients assigned to placebo groups. The pooled rate of response to placebo, among all RCTs, for complete fistula closure was 15.6% (95% CI, 10.9%-20.9%), with significant heterogeneity (I(2) = 62.5%, P = .001). The pooled rate of response to placebo for partial fistula closure or response in 9 trials, comprising 423 patients, was 18.3% (95% CI, 14.8%-22.1%). Rates of response to placebo were significantly lower in trials with shorter durations of therapy and shorter intervals to assessment of fistula closure. Neither exposure to the pharmacologic agent during the induction phase of the same (or related) RCT nor concomitant medications had any effect. CONCLUSIONS: In a meta-analysis of rate of response to placebo in patients with fistulizing CD, we found that fistulae closed in almost 1/6 patients given placebo in RCTs of pharmacologic agents. Future research should identify characteristics of patients that predict response to placebo.

13 Review American Gastroenterological Association Institute technical review on the use of thiopurines, methotrexate, and anti-TNF-α biologic drugs for the induction and maintenance of remission in inflammatory Crohn's disease. 2013

Dassopoulos, Themistocles / Sultan, Shahnaz / Falck-Ytter, Yngve T / Inadomi, John M / Hanauer, Stephen B. ·Division of Gastroenterology, Washington University School of Medicine, Saint Louis, Missouri. ·Gastroenterology · Pubmed #24267475.

ABSTRACT: -- No abstract --

14 Review Treat the patient or treat the disease? 2012

Hanauer, Stephen B / Kirsner, Joseph B. ·Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine and Clinical Pharmacology, University of Chicago, Chicago, Ill., USA. shanauer@medicine.bsd.uchicago.edu ·Dig Dis · Pubmed #22796805.

ABSTRACT: Our therapeutic goals for the treatment of ulcerative colitis and Crohn's disease are evolving. Until the last decade the goals were primarily the treatment of symptoms. Regulatory approval for ulcerative colitis therapies have been based on short-term improvements in clinical indices and, most recently, the ability to heal the colonic mucosa, whereas approval for Crohn's disease therapies have been based on reductions in the CDAI (Crohn's Disease Activity Index). Over the past decade there has been increasing evidence in favor of more 'objective' measures of biologic disease activity including biomarkers such as C-reactive protein and mucosal healing in Crohn's disease and the histologic resolution of active inflammation in ulcerative colitis. The objective changes have provided expanded therapeutic goals based on longer-term maintenance therapies with the potential to modify the chronic disease behavior and to reduce pharmacoeconomic costs (reductions in hospitalizations, surgeries and neoplasia).

15 Review Management of inflammatory bowel disease: past, present and future. 2012

Keyashian, Kian / Annunziata, Maria Laura / Sakuraba, Atsushi / Hanauer, Stephen. ·Section of Gastroenterology, Hepatology & Nutrition, Department of Medicine, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA. ·Expert Rev Clin Immunol · Pubmed #22607175.

ABSTRACT: -- No abstract --

16 Review Complications of peristomal recurrence of Crohn's disease: a case report and a review of literature. 2012

Hoentjen, Frank / Colwell, Janice C / Hanauer, Stephen B. ·Radboud University Medical Center, Nijmegen, the Netherlands. frankhoentjen@gmail.com ·J Wound Ostomy Continence Nurs · Pubmed #22552106.

ABSTRACT: Patients with Crohn's disease and colonic inflammation that proves refractory to medical therapy often require a proctocolectomy and end ileostomy. Disease recurrence can occur despite creation of an end ileostomy and may lead to peristomal complications such as fistula formation, abscesses, stoma retraction, or strictures. We present the case of a 51-year-old man with medically refractory ileocolonic Crohn's disease who underwent a proctocolectomy with end ileostomy. The disease course was complicated by recurrence of ileal Crohn's disease despite biological therapy. The patient presented with peristomal complications including an enterocutaneous fistula, stoma retraction, and an ileal stricture necessitating surgical revision of the ileostomy. Review of literature confirms an approximately 30% risk of recurrence of Crohn's disease after an end ileostomy. A penetrating phenotype and preexisting ileal disease are risk factors for disease recurrence. A thorough evaluation of the stoma/peristomal area and evaluation of the small bowel by ileoscopy and small bowel imaging are required to assess the extent of disease and extraluminal complications such as stomal retraction and fistulas that require further surgical intervention. While postoperative medical treatment with immunosuppression or biological therapy is often employed, these therapies are unproven to prevent postoperative recurrence in the setting of a stoma.

17 Review Shared experiences and best practices in the management of rheumatoid arthritis and Crohn's disease. 2011

Kavanaugh, Arthur F / Mayer, Lloyd F / Cush, John J / Hanauer, Stephen B. ·Center for Innovative Therapy, Division of Rheumatology, Allergy, and Immunology, Department of Medicine, University of California at San Diego, San Diego, California, USA. ·Am J Med · Pubmed #21531240.

ABSTRACT: -- No abstract --

18 Review An evidence-based systematic review on medical therapies for inflammatory bowel disease. 2011

Talley, Nicholas J / Abreu, Maria T / Achkar, Jean-Paul / Bernstein, Charles N / Dubinsky, Marla C / Hanauer, Stephen B / Kane, Sunanda V / Sandborn, William J / Ullman, Thomas A / Moayyedi, Paul / Anonymous3450691. ·Department of Medicine, Faculty of Health, University of Newcastle, Callaghan, NSW 2308, Australia. Nicholas.Talley@newcastle.edu.au ·Am J Gastroenterol · Pubmed #21472012.

ABSTRACT: -- No abstract --

19 Review Assessing response and loss of response to biological therapies in IBD. 2011

Yanai, Henit / Hanauer, Stephen B. ·Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. ·Am J Gastroenterol · Pubmed #21427713.

ABSTRACT: OBJECTIVES: The advent of biological therapies for inflammatory bowel disease (IBD) began in 1998 with the approval of infliximab for the treatment of refractory (to conventional agents) Crohn's disease (CD). Since then, the indications for anti-tumor necrosis factor-α (anti-TNFα) therapy have increased to include induction and maintenance of clinical responses and remissions for luminal and fistulizing CD, the treatment of children with CD, and the treatment of adults with ulcerative colitis. Additional utilities of biological therapies have included demonstrable mucosal healing, improvement in quality of life, reduction in surgeries and hospitalizations, and the treatment of extraintestinal manifestations of IBD including central and peripheral arthritis and pyoderma gangrenosum. Natalizumab has also been approved for the treatment of refractory Crohn's in patients who have failed conventional agents and anti-TNFα therapies. Unfortunately, despite the overall effectiveness of biological agents in a spectrum of indications for IBD, a significant proportion of patients do not respond or lose response over time. In this review, we intend to appraise the latest evolution in treatment strategies in IBD and to suggest an evidence-based approach and risk stratification while coping with cases of non-responders or loss of response to biological therapies. METHODS: We conducted a literature search of English publications listed in the electronic databases of MEDLINE (source PUBMED) and constructed an analytical review based on definitions of response and loss of response, considering potential responsible mechanisms, clinical assessment tools, and finally recommending a practical approach for its prevention and management. RESULTS: Favorable clinical outcome appears to be the consequence of sustained therapeutic drug levels, and the current literature supports a practice of dose adjustments. When immunogenicity develops to a single biological agent, response can be regained by introduction of an alternative biological agent of the same or different class. Efficacy is reduced with second-line agents either within or across classes compared with naive patients. In the absence of direct measurement of drug levels and anti-drug antibodies, clinical judgment is necessary to assess the mechanisms of loss of response, and more empiric decision making may be necessary to determine the choice of second-line biological agents. Optimal treatment strategies are still controversial. CONCLUSIONS: It is essential to recognize the spectrum of mechanisms affecting response and loss of response to form a logical and efficient management algorithm, and, perhaps, it is time to incorporate the measurement of trough levels and anti-drug antibodies in the strategy of such an assessment. Prospective controlled trials are direly needed to investigate the optimal tailored management in individual patients who lose response.

20 Review Efficacy of biological therapies in inflammatory bowel disease: systematic review and meta-analysis. 2011

Ford, Alexander C / Sandborn, William J / Khan, Khurram J / Hanauer, Stephen B / Talley, Nicholas J / Moayyedi, Paul. ·Leeds Gastroenterology Institute, Leeds General Infirmary, Leeds, UK. alexf12399@yahoo.com ·Am J Gastroenterol · Pubmed #21407183.

ABSTRACT: OBJECTIVES: Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory disorders of the gastrointestinal tract of unknown etiology. Evidence for treatment of the condition with biological therapies exists, but no systematic review and meta-analysis has examined this issue in its entirety. METHODS: MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through to December 2010). Trials recruiting adults with active or quiescent CD or UC and comparing biological therapies (anti-tumor necrosis factor-α (TNFα) antibodies or natalizumab) with placebo were eligible. Dichotomous symptom data were pooled to obtain relative risk (RR) of failure to achieve remission in active disease and RR of relapse of activity in quiescent disease once remission had occurred, with a 95% confidence interval (CI). RESULTS: The search strategy identified 3,061 citations, 27 of which were eligible. Anti-TNFα antibodies and natalizumab were both superior to placebo in inducing remission of luminal CD (RR of no remission=0.87; 95% CI 0.80-0.94 and RR=0.88; 95% CI 0.83-0.94, respectively). Anti-TNFα antibodies were also superior to placebo in preventing relapse of luminal CD (RR of relapse=0.71; 95% CI 0.65-0.76). Infliximab was superior to placebo in inducing remission of moderate to severely active UC (RR=0.72; 95% CI 0.57-0.91). CONCLUSIONS: Biological therapies were superior to placebo in inducing remission of active CD and UC, and in preventing relapse of quiescent CD.

21 Review Practical application of anti-TNF therapy for luminal Crohn's disease. 2011

Kamm, Michael A / Ng, Siew C / De Cruz, Peter / Allen, Patrick / Hanauer, Stephen B. ·St Vincent's Hospital and University of Melbourne, Melbourne, Australia. mkamm@unimelb.edu.au ·Inflamm Bowel Dis · Pubmed #21337669.

ABSTRACT: Anti-tumor necrosis factor (TNF) therapy to treat inflammatory bowel disease has been available for more than a decade. Although extensive data on the outcome of anti-TNF therapy from individual clinical trials and patient cohorts are available, integrated guidance on the best use of such therapy to achieve optimal clinical outcomes when managing patients with luminal Crohn's disease is lacking. This review combines published data to establish practical strategies for anti-TNF therapy with respect to effective and safe timing of introduction, use of concurrent immunosuppressive therapy, dose escalation, managing relapse, changing drugs, pregnancy and breast feeding, and stopping drug treatment.

22 Review Assessment of non-cirrhotic portal hypertension associated with thiopurine therapy in inflammatory bowel disease. 2011

Calabrese, Emma / Hanauer, Stephen B. ·University of Chicago, Section of Gastroenterology, Hepatology and Nutrition, Chicago, IL 60637, USA. ·J Crohns Colitis · Pubmed #21272804.

ABSTRACT: Thiopurines represent an effective and widely used immunosuppressant in the therapeutic armamentarium of inflammatory bowel disease. However up to 25% of patients may be unable to continue the drug due to side effects. The incidence of hepatotoxicity associated with thiopurine use is reported between 0% and 32%. Veno-occlusive disease, peliosis hepatis, perisinusoidal fibrosis and nodular regenerative hyperplasia have all been described with thiopurines. Recent trials of 6-tioguanine, although successful in patients with allergies to azathioprine or mercaptopurine, have been compromised by increased hepatotoxicity, either veno-occlusive disease or nodular regenerative hyperplasia. We describe a report of nodular regenerative hyperplasia in a Crohn's disease patient associated with 6-mercaptopurine therapy and have reviewed the management and the literature regarding this complication. Our report strengthens the importance of further safety studies to evaluate the etiology, prevalence, risk factors and screening modalities for hepatotoxicity, in particular of nodular regenerative hyperplasia, in patients treated with thiopurines for inflammatory bowel disease.

23 Review The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn's and Colitis Organization: when to start, when to stop, which drug to choose, and how to predict response? 2011

D'Haens, Geert R / Panaccione, Remo / Higgins, Peter D R / Vermeire, Severine / Gassull, Miquel / Chowers, Yehuda / Hanauer, Stephen B / Herfarth, Hans / Hommes, Daan W / Kamm, Michael / Löfberg, Robert / Quary, A / Sands, Bruce / Sood, A / Watermeyer, G / Lashner, Bret / Lémann, Marc / Plevy, Scott / Reinisch, Walter / Schreiber, Stefan / Siegel, Corey / Targan, Stephen / Watanabe, M / Feagan, Brian / Sandborn, William J / Colombel, Jean Frédéric / Travis, Simon. ·Department of Gastroenterology, Academic Medical Centre, Amsterdam, The Netherlands. g.dhaens@amc.uva.nl ·Am J Gastroenterol · Pubmed #21045814.

ABSTRACT: The advent of biological therapy has revolutionized inflammatory bowel disease (IBD) care. Nonetheless, not all patients require biological therapy. Selection of patients depends on clinical characteristics, previous response to other medical therapy, and comorbid conditions. Availability, reimbursement guidelines, and patient preferences guide the choice of first-line biological therapy for luminal Crohn's disease (CD). Infliximab (IFX) has the most extensive clinical trial data, but other biological agents (adalimumab (ADA), certolizumab pegol (CZP), and natalizumab (NAT)) appear to have similar benefits in CD. Steroid-refractory, steroid-dependent, or complex fistulizing CD are indications for starting biological therapy, after surgical drainage of any sepsis. For fistulizing CD, the efficacy of IFX for inducing fistula closure is best documented. Unique risks of NAT account for its labeling as a second-line biological agent in some countries. Patients who respond to induction therapy benefit from systematic re-treatment. The combination of IFX with azathioprine is better than monotherapy for induction of remission and mucosal healing up to 1 year in patients who are naïve to both agents. Whether this applies to other agents remains unknown. IFX is also effective for treatment-refractory, moderate, or severely active ulcerative colitis. Patients who have a diminished or loss of response to anti-tumor necrosis factor (TNF) therapy may respond to dose adjustment of the same agent or switching to another agent. Careful consideration should be given to the reasons for loss of response. There are insufficient data to make recommendations on when to stop anti-TNF therapy. Preliminary evidence suggests that a substantial proportion of patients in clinical remission for >1 year, without signs of active inflammation can remain in remission after stopping treatment.

24 Review Aminosalicylates for induction of remission or response in Crohn's disease. 2010

Lim, Wee-Chian / Hanauer, Stephen. ·Department of Gastroenterology and Hepatology, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore, Singapore, S 308433. ·Cochrane Database Syst Rev · Pubmed #21154400.

ABSTRACT: BACKGROUND: Controlled clinical trials investigating the efficacy of aminosalicylates for the treatment of mildly to moderately active Crohn's disease have yielded conflicting results. A systematic review was conducted to critically examine current available data on the efficacy of sulfasalazine and mesalamine for inducing remission or clinical response in patients with mildly to moderately active Crohn's disease. OBJECTIVES: To evaluate the efficacy of aminosalicylates compared to placebo, corticosteroids, and other aminosalicylates (alone or in combination with corticosteroids) for the treatment of mildly to moderately active Crohn's disease. SEARCH STRATEGY: Separate MEDLINE (1966-July 2010), Cochrane Central Register of Controlled Trials (CENTRAL; Issue 3, 2010) and EMBASE database searches (1985-July 2010) of all relevant English and non-English language articles were performed, followed by manual searches of the reference list from potentially relevant papers and review articles, as well as proceedings from annual meetings (1991-2010) of the American Gastroenterological Association (AGA) and American College of Gastroenterology (ACG). SELECTION CRITERIA: Randomized controlled trials that evaluated the efficacy of sulfasalazine or mesalamine in the treatment of mildly to moderately active Crohn's disease compared to placebo, corticosteroids, and other aminosalicylates (alone or in combination with corticosteroids) were included. DATA COLLECTION AND ANALYSIS: Data extraction and assessment of methodological quality of each selected study was independently performed by the investigators and any disagreement was resolved by discussion and consensus. The primary outcome measure was a well defined clinical endpoint of induction of remission or response to treatment. Nineteen studies met the inclusion criteria and were analyzed. Pooled relative risks (RR) for inducing remission or clinical response and their 95% confidence intervals were calculated (random effects model) where appropriate. MAIN RESULTS: Sulfasalazine was more likely to induce remission (RR 1.38; 95% CI 1.02 to 1.87; n = 263) compared to placebo with benefit confined mainly to patients with colitis. Sulfasalazine was less effective than corticosteroids (RR 0.66; 95% CI 0.53 to 0.81; n = 260). Olsalazine was less effective than placebo in a single trial. Low dose mesalamine (1 to 2 g/day) was not superior to placebo (RR = 1.46, 95% CI 0.89-2.40; n = 302) and was less effective than corticosteroids. High dose mesalamine (3 to 4.5 g/day) was not superior to placebo for induction of remission (RR 2.02; 95% CI 0.75 to 5.45) or response (Weighted Mean Difference -19.8 points; 95% CI -46.2 to 6.7; n = 615). In a single randomized controlled trial, 5-ASA was inferior to budesonide (RR 0.56; 95% CI 0.40 to 0.78). No statistically significant difference was found between high dose mesalamine and conventional corticosteroids (RR 1.04; 95% CI 0.79 to 1.36; n = 178). However, relatively few patients were available for analysis. There was a lack of good quality clinical trials comparing sulfasalazine with other mesalamine formulations. AUTHORS' CONCLUSIONS: Sulfasalazine has modest efficacy compared to placebo and is inferior to corticosteroids for the treatment of mild to moderately active Crohn's disease. Olsalazine and low dose mesalamine (1 to 2 g/day) are not superior to placebo. High dose mesalamine (3 to 4.5 g/day) is not more effective than placebo for inducing response or remission. High dose mesalamine was inferior to budesonide for inducing remission in a single trial. In conclusion, sulfasalazine shows modest efficacy for the treatment of active Crohn's disease. However, the existing data show little benefit for 5-aminosalicylates.

25 Review Medical management of Crohn's disease: treatment algorithms 2009. 2009

Hanauer, Stephen B. ·Medicine and Clinical Pharmacology, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medical Center, Chicago, Ill. 60637, USA. shanauer@uchicago.edu ·Dig Dis · Pubmed #19897971.

ABSTRACT: There has been a continual evolution of therapy for Crohn's disease (CD) over the past decade since the introduction of biological therapies targeting tumor necrosis factor-alpha. Conventional agents continue to be safe and effective for patients with mild to moderately active CD and, in population series, less than half of the patients with CD require corticosteroid therapy. In contrast, patients presenting at young ages, those with extensive disease, deep ulcerations, transmural complications or extraintestinal complications that require corticosteroid therapy have a poor prognosis. Introduction of immunosuppressives late in the course or for patients with steroid-dependent or steroid-refractory disease have not changed the 'natural history' of CD or the need for eventual surgical resections. There is increasing evidence that early intervention with immunosuppressives or biologic agents at the same time as corticosteroids, or biologic agents targeting tumor necrosis factor or adhesion molecules, can have rapid and prolonged benefits, including steroid sparing, reductions in hospitalizations and, perhaps, reductions in the need for surgery. Treatment should be optimized according to the patient status and response with whichever level of therapy is introduced and maintained.

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