Crohn Disease: Hanauer SB

Lichtenstein GR, Hanauer SB, Sandborn WJ, Anonymous00070. · Department of Medicine, Division of Gastroenterology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. · Am J Gastroenterol. · Pubmed #19174807 No free full text.

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.

Hanauer SB, Sandborn W, Anonymous00243. · University of Chicago Pritzker School of Medicine, Illinois 60637, USA. · Am J Gastroenterol. · Pubmed #11280528 No free full text.

This publication has no abstract.

Hanauer SB. · No affiliation provided · Nat Clin Pract Gastroenterol Hepatol. · Pubmed #18670441 No free full text.

This publication has no abstract.

Hanauer SB. · No affiliation provided · Nat Clin Pract Gastroenterol Hepatol. · Pubmed #17768393 No free full text.

This publication has no abstract.

Hanauer SB, Sandborn WJ. · No affiliation provided · Gut. · Pubmed #17303600 No free full text.

This publication has no abstract.

Hanauer SB. · No affiliation provided · Nat Clin Pract Gastroenterol Hepatol. · Pubmed #16951659 No free full text.

This publication has no abstract.

Hanauer SB. · No affiliation provided · Nat Clin Pract Gastroenterol Hepatol. · Pubmed #16355136 No free full text.

This publication has no abstract.

Hanauer SB, Thisted RA. · No affiliation provided · Gastroenterology. · Pubmed #15940649 No free full text.

This publication has no abstract.

Hanauer SB. · Department of Medicine and Clinical Pharmacology, University of Chicago, Chicago, Illinois, USA. · Inflamm Bowel Dis. · Pubmed #15905710 No free full text.

Abstract: Mesalamine has a well-established role in the management of ulcerative colitis. However, its role in the management of Crohn's disease (CD) is less clear. Studies evaluating its therapeutic value in CD have produced both positive and negative results. Meta-analyses have not clarified the situation, possibly because they have combined studies of different design. This debate critically examines the evidence for and against the use of mesalamine in CD.

Shah SB, Hanauer SB. · Section of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Chicago, Chicago, Illinois, USA. · Rev Gastroenterol Disord. · Pubmed #18192964 No free full text.

Abstract: Diarrhea continues to be a prevalent symptom in patients with inflammatory bowel disease (IBD), requiring a wide differential diagnosis to define the pathophysiologic mechanisms in individual patients. It is essential that physicians properly evaluate complaints of diarrhea by assessing both patient symptoms and potential physiologic impacts on fluid and electrolyte status. Underlying mechanisms of diarrhea with IBD are the location, extent, and severity of inflammation; malabsorption; altered motility; and iatrogenic causes such as medications, diet, and antibiotic-associated colitis (eg, Clostridium difficile). When treating diarrhea, physicians need to control inflammatory activity using appropriate treatment algorithms. Therapies include aminosalicylates, corticosteroids, immune modifiers, and, most recently, biologic treatment. Other medications, including loperamide, diphenoxylate, codeine sulfate, and tinctures of opium, slow motility and increase the absorption of fluids and nutrients. For iatrogenic issues, medications that cause diarrhea should be withdrawn and individual diets modified. Not all diarrheas in the IBD patient are the same; therefore, it is essential to tailor therapies according to presumed etiologies. Antidiarrheal agents are not recommended in extremely ill patients and those with known hypersensitivity or evidence of obstruction or colonic dilation, fever, or abdominal tenderness. Concomitant use of loperamide with diphenoxylate and atropine should be avoided in early pregnancy.

Hanauer SB. · Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Chicago, Illinois, USA. · Rev Gastroenterol Disord. · Pubmed #17392635 No free full text.

Abstract: The current Crohn's disease treatment algorithm involves a "step-up" approach in which conventional medications such as corticosteroids are given first and anti-tumor necrosis factor-a (TNF-a) agents are reserved for refractory cases. Although this approach may seem to be cost-efficient, recent studies have shown that "top-down" therapy using anti-TNF-a agents in newly diagnosed patients improves long-term rates of mucosal healing, a therapeutic endpoint that correlates with reduced hospitalizations and surgeries, thereby reducing overall costs and enhancing patients' quality of life. Another reason the step-up approach has been favored over the top-down is concern about side effects; however, a multivariate logistic regression analysis of patients treated with or without infliximab showed no differences in mortality, serious infections, or malignancies between the 2 groups. Moreover, newer anti-TNF-a agents, such as adalimumab and certolizumab pegol, have the potential to reduce the risk of immunogenicity and the associated infusion reactions and loss of response, as well as reducing autoimmunity associated with infliximab therapy. The potential advantages of "reversing" our current therapeutic pyramid/algorithm for the treatment of Crohn's disease include early disease stabilization and disease modification, minimization of complications such as strictures and fistulae that lead to the need for surgery, reduction of postoperative recurrence, and avoidance of the ubiquitous complications of corticosteroid therapy.

Hanauer SB. · Section of Gastroenterology and Nutrition, Department of Medicine, University of Chicago Medical Center, Chicago, Illinois, USA. · Rev Gastroenterol Disord. · Pubmed #15580149 No free full text.

Abstract: The past decade has brought forth a series of novel biologic agents targeting tumor necrosis factor (TNF) for the treatment of Crohn's disease. The introduction of infliximab has paved the way for additional anti-TNF strategies that have the potential to build on that drug's efficacy and safety profile. However, the anti-TNF strategies might not have identical efficacy and safety profiles and might differ in dosing compared with therapy for rheumatoid arthritis. Most recently, adalimumab has been approved by the US Food and Drug Administration for the treatment of rheumatoid arthritis and is undergoing evaluation in Crohn's disease, with promising initial results. This review discusses the results of controlled clinical trials of anti-TNF agents for Crohn's disease.

Lichtenstein GR, Hanauer SB, Kane SV, Present DH. · University of Pennsylvania School of Medicine, Philadelphia, PA, USA. · Inflamm Bowel Dis. · Pubmed #15475770 No free full text.

Abstract: Crohn's disease is an idiopathic, chronic inflammatory disorder of the digestive tract with heterogeneous clinical presentations. Crohn's is currently not a curable disease, and patients are faced with a lifetime of recurrent disease flare-ups and remissions. Management strategies for Crohn's must therefore be targeted toward lifelong management, taking into consideration not only the short-term but also the long-term aspects of the disease. With this in mind, here we review the classifications and natural history of Crohn's disease and discuss possible predictive factors for the disease evolution in a patient. Here we also evaluate the current preferable treatment practices, based on scientifically valid research and collective clinical experience, for the management of mild to moderate Crohn's disease.

Lim WC, Hanauer SB. · Section of Gastroenterology and Nutrition, Department of Medicine, University of Chicago Medical Center, Chicago, Illinois, USA. · Rev Gastroenterol Disord. · Pubmed #15359211 No free full text.

Abstract: Aminosalicylates have been shown to exhibit a wide range of anti-inflammatory and immunomodulatory properties. Since the discovery of sulfasalazine's efficacy in ulcerative colitis and the subsequent development of sulfa-free mesalamine delivery systems, aminosalicylates have evolved to become an integral part of our therapeutic armamentarium and are now first-line therapies for the treatment of mildly to moderately active inflammatory bowel disease and for maintenance of remissions after successful induction therapy. Despite the substantial body of evidence supporting the use of aminosalicylates in ulcerative colitis and Crohn's disease, gaps in our evidence base and controversies surrounding aminosalicylates clinical application have emerged. In this review, issues of dose response and optimization of the treatment regimen in ulcerative colitis, the discrimination between oral mesalamine formulations in left-sided colitis, and their efficacy in active and quiescent Crohn's disease are discussed.

Hanauer SB. · University of Chicago, Section of Gastroenterology, IL 60637, USA. · Aliment Pharmacol Ther. · Pubmed #15352896 links to  free full text

Abstract: Aminosalicylate therapy for ulcerative colitis remains a foundational strategy for the induction and maintenance of remission for mild to moderate disease. Although it seems clear that topical mesalazine (mesalamine) is the most efficacious approach to distal ulcerative colitis, recent trials with orally delivered azo conjugates suggest that there may be an advantage over pH-released mesalazine as a first-line approach to active disease. No such comparisons are available for azo products and the prolonged-release formulation, Pentasa. However, recent meta-analyses have demonstrated that, although there is little difference in systemic exposure between marketed products, luminal concentrations may vary. In maintenance therapy, aminosalicylates remain the standard approach after aminosalicylate-induced remission. A number of gaps remain in the evidence base with regard to the optimal dosing of oral mesalazine as a maintenance agent, whether oral mesalazine can maintain remissions after rectal mesalazine induction, and the dose-response and efficacy of aminosalicylates after steroid- or ciclosporin-induced remissions. Although aminosalicylates have been advocated for several decades in Crohn's disease, a number of controversies have evolved since the original trials with sulfasalazine in active Crohn's disease. The original trials demonstrated benefits for sulfasalazine in colonic involvement, but controlled trial evidence for the role of sulfasalazine as maintenance therapy has not been as firmly established. In addition, although oral mesalazine has been demonstrated in controlled trials to be superior to placebo in mild to moderate disease, it is less efficacious than corticosteroids at inducing remissions. The maintenance benefits of mesalazine appear to be limited to patients 'induced into remission' with mesalazine and in some post-operative settings.

Lim WC, Hanauer SB. · Section of Gastroenterology, Department of Medicine, University of Chicago Hospitals, Chicago, Illinois, USA. · Rev Gastroenterol Disord. · Pubmed #15184826 No free full text.

Abstract: Ulcerative colitis and Crohn's disease, the idiopathic inflammatory bowel diseases (IBD), are thought to represent genetically determined, dysregulated immune responses to otherwise innocuous luminal antigens. Although progress in research has advanced our understanding of the immunopathogenesis and begun to elucidate genetic contributions toward susceptibility, limitations of current medical approaches continue to drive the search for better therapeutic agents. Most recently, the introduction of infliximab has heralded a new era of evolving biologically targeted treatments for IBD. Infliximab is currently the only biologic agent approved for the treatment of inflammatory and fistulizing Crohn's disease, but ongoing research continues to generate new biologic agents targeted at specific pathogenic mechanisms involved in the inflammatory process. Undoubtedly, with the success of infliximab, the role of biologic therapy will continue to expand in the future treatment of IBD.

Harrell LE, Hanauer SB. · Section of Gastroenterology and Nutrition, University of Chicago Medical Center, 5841 South Maryland Avenue, MC 4076, Chicago, IL 60637, USA. · Gastroenterol Clin North Am. · Pubmed #15177540 No free full text.

Abstract: The role of the aminosalicylates for induction therapy of mild moderate ulcerative colitis and as maintenance treatment has been substantiated by a large series of controlled clinical trials and confirmatory meta-analyses. Both sulfasalazine and newer derivatives are effective in preventing relapses. It remains to be determined whether certain high-risk groups of patients may benefit from higher doses of mesalamine induction or maintenance therapy. Mesalamine derivatives are also of benefit in the treatment of Crohn's disease. Sulfasalazine is likely not effective in the maintenance of Crohn's disease, although other mesalamine formulations continue to show some prophylactic activity after mesalamine induced remissions and for patients with disease of the ileum who have undergone surgical resection.

Sandborn WJ, Fazio VW, Feagan BG, Hanauer SB, Anonymous00031. · Clinical Practice Committee, AGA National Office, c/o Membership Department, 4930 Del Ray Avenue, Bethesda, MD 20814, USA. · Gastroenterology. · Pubmed #14598268 No free full text.

This publication has no abstract.

Hanauer SB, Present DH. · Section of Gastroenterology and Nutrition, University of Chicago, Pritzker School of Medicine, Chicago, IL, USA. · Rev Gastroenterol Disord. · Pubmed #12776005 No free full text.

Abstract: Ulcerative colitis (UC) and Crohn's disease (CD), collectively known as inflammatory bowel disease (IBD), afflict an estimated one million Americans and produce symptoms that impair quality of life and ability to function. Progress in IBD management strategies has led to optimized approaches for achieving the two primary clinical goals of therapy: induction and maintenance of remission. Although surgery is indicated to treat refractory disease or specific complications, pharmacotherapy is the cornerstone of IBD management. The efficacy of aminosalicylates for induction of remission in mild to moderate UC and CD is well established, as is their role for maintenance of remission in UC. The sulfa-free mesalamine formulation offers an adverse effect profile similar to that of placebo, enabling the administration of higher, more effective doses. Although corticosteroids provide potent anti-inflammatory effects, their benefits are countermanded by the risk of intolerable and serious adverse effects, and they are ineffective for maintenance therapy. Other agents effective in inducing or maintaining remission are azathioprine, 6-mercaptopurine, infliximab, cyclosporine, methotrexate, and antibiotics. Ongoing clinical trials of experimental therapies will generate new tools for IBD treatment. Currently, a broad range of options allows physicians to tailor treatment to each patient's needs and preferences. Such considerations are essential for maximizing adherence to therapy.

Hanauer SB. · University of Chicago, 5841 S Maryland Ave, MC4076, Chicago, Il 60637, USA. · Best Pract Res Clin Gastroenterol. · Pubmed #12617888 No free full text.

Abstract: The concept of a 'step-up' or 'top-down' approach to the treatment of Crohn's disease has evolved from the impact of novel anti-TNF (anti-tumour necrosis factor) therapies that have been effective for patients who are refractory to other medical treatments. In addition, the potential to produce mucosal healing with anti-TNF treatments without the well-recognized systemic complications of glucocorticoid therapy has created debate as to whether earlier, more aggressive, therapies should be advocated. This controversy arises at a time when the concept of sequential therapy to induce and maintain remissions for Crohn's disease has begun to be accepted and precedes our ability to define the concept of disease modification or predict the natural history of Crohn's disease based upon clinical, pathological, molecular orgenetic criteria. Evidence for therapeutic efficacy in Crohn's disease is presented as a prologue to considerations necessary to determine the benefits and risks of early aggressive treatment versus sequential approaches based upon disease severity.

Sandborn WJ, Hanauer SB. · Inflammatory Bowel Disease Clinic, Division of Gastroenterology and Hepatology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA. · Am J Gastroenterol. · Pubmed #12492177 No free full text.

Abstract: Induction therapy with infliximab is indicated for treatment of signs and symptoms, and induction and maintenance of remission in patients with moderate to severely active inflammatory Crohn's disease with an inadequate response to conventional therapy, and for reduction in the number of draining fistulas in patients with fistulizing Crohn's disease. Emerging indications for infliximab therapy in patients with Crohn's disease include maintenance of fistula improvement (reduction in the number of draining perianal or enterocutaneous fistulas) and complete fistula response (no draining fistulas) in patients with fistulizing Crohn's disease, steroid sparing in steroid-treated patients, early use in hospitalized patients who have not failed conventional medical therapy where there is either a severe clinical presentation or a rapid onset of action is desired, and in a variety of unusual and extra-intestinal manifestations of Crohn's disease. An infliximab dose of 5 mg/kg is recommended initally, but some patients who require maintenance dosing may benefit from increasing the infliximab dose over a range of 5-10 mg/kg. An induction regimen of 3 doses at 0, 2, and 6 weeks is the preferred dosing strategy for inducing remission. The optimal dosing interval for patients who require retreatment appears to be every 8 weeks for most patients. Concomitant immunosuppressive therapy with azathioprine, 6-mercaptopurine, or methotrexate may result in improved outcomes due to a reduction in the frequency of human anti-chimeric antibody formation, acute infusion reactions, and a reduced risk of delayed hypersensitivity-like reactions and formation of antinuclear antibodies. Pretreatment with diphenhydramine (and in selected cases of acetaminophen and, rarely, corticosteroids) is recommended in patients with a history of infusion reactions and patients at risk for delayed hypersensitivity-like reactions. Patients with evidence of active infection should not receive infliximab until the infection is adequately treated, and all patients should be screened for tuberculosis prior to initiating infliximab therapy.

Harrison J, Hanauer SB. · Department of Medicine and Clinical Pharmacology, Section of Gastroenterology and Nutrition, Pritzker School of Medicine, University of Chicago, Chicago, Illinois, USA. · Gastroenterol Clin North Am. · Pubmed #12122730 No free full text.

Abstract: Crohn's disease is not medically (and is rarely surgically) curable. Patients do, however, live a normal life span. The goal of therapy is to optimize the quality of life, minimize disease activity and disease-related complications, and avoid therapeutic toxicity.

Sandborn WJ, Feagan BG, Hanauer SB, Lochs H, Löfberg R, Modigliani R, Present DH, Rutgeerts P, Schölmerich J, Stange EF, Sutherland LR. · The Clinical Trials Task Force of the International Organization of Inflammatory Bowel Disease. · Gastroenterology. · Pubmed #11832465 No free full text.

This publication has no abstract.

Achkar JP, Hanauer SB. · Department of Gastroenterology, The Cleveland Clinic Foundation, Ohio 44195, USA. · Am J Gastroenterol. · Pubmed #10811318 No free full text.

Abstract: Clinical recurrence of Crohn's disease after surgical resection is a significant problem, with reported rates as high as 55% at 5 yr and 76% at 15 yr. Specific factors that predispose to postoperative recurrence of Crohn's disease have not been well defined. In addition, the underlying pathophysiology of recurrent disease and the reason for its localization to the neoterminal ileum are not well understood. Various operative techniques have been evaluated but none, aside from formation of an ostomy, has been shown to reduce the risk of recurrence. In contrast, there is increasing evidence that postoperative medical therapy has the potential to decrease the risk of postoperative recurrence. Historically, sulfasalazine may have a modest effect on reducing postoperative recurrence of ileal or ileocolonic disease. However, 5-ASA preparations that can selectively deliver mesalamine to the small bowel or anastomotic margin should be more effective. Indeed, in several studies and as confirmed by a meta-analysis, mesalamine has been demonstrated to reduce significantly postoperative recurrence of Crohn's disease. Metronidazole and 6-mercaptopurine or azathioprine also seem to be of benefit in postoperative prophylaxis of disease recurrence, but additional controlled studies are required to define better the efficacy and dose-response of these agents. Corticosteroids are ineffective at reducing postoperative recurrence.

Hanauer SB. · University of Chicago, Illinois, USA. · Aliment Pharmacol Ther. · Pubmed #10597335 links to  free full text

Abstract: Infliximab, a chimeric monoclonal antibody to tumour necrosis factor-alpha, contains murine protein elements and targets the immune system, raising concerns about the potential for immune sensitization and immunosuppressive sequelae. However, long-standing inflammatory disease with high activity and chronic immunosuppressant therapy can also predispose patients to immunosuppressive sequelae. Patients with Crohn's disease, rheumatoid arthritis and other indications received single or multiple doses of infliximab and their condition was followed for up to 3 years. Adverse events, most frequently headache, nausea, and upper respiratory tract infection, were generally mild and occurred in 76% of infliximab-treated patients vs. 57% of placebo-treated recipients. Human antichimeric antibodies developed in 13% of patients, increasing the potential for subsequent infusion reactions. Antibodies to double-stranded DNA developed in a small percentage of patients. Other antinuclear antibodies characteristic of serum lupus erythematosus were not found; no patient developed a true lupus syndrome and no other autoimmune disorders were reported. Infliximab is not associated with typical immunosuppressive sequelae, such as infections and malignancy, or with autoimmune disorders. Infliximab therapy was well tolerated, serious adverse events were infrequent, successfully managed with medication and without sequelae, and overall mortality was within the expected incidence for this patient population.