Ulcerative Colitis: Sandborn WJ

Sandborn WJ. · No affiliation provided · Am J Gastroenterol. · Pubmed #12492172 No free full text.

This publication has no abstract.

Panaccione R, Rutgeerts P, Sandborn WJ, Feagan B, Schreiber S, Ghosh S. · Department of Medicine, University of Calgary, Calgary, AB, Canada. · Aliment Pharmacol Ther. · Pubmed #18532990 No free full text.

Abstract: BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the intestine, which frequently require surgery for complications or failure of medical therapy. AIM: To seek evidence and provide direction for clinicians on optimal strategies to enable steroid free remission in inflammatory bowel disease. METHODS: Scientific literature was reviewed using MEDLINIE with a specific focus on medical therapies for inducing and maintaining remission of CD and UC. The results were discussed at a roundtable meeting to reach a consensus on key issues. RESULTS: Several therapies have demonstrated efficacy for the treatment of active, moderate-to-severe CD and UC. These include agents, which induce remission [corticosteroids, infliximab and adalimumab (CD only)] or maintain remission and spare corticosteroids [azathioprine, mercaptopurine, methotrexate (CD only), infliximab and adalimumab (CD only)]. Wide variability exists in the use of these agents. CONCLUSION: Treatment strategy algorithms are developed for use of these therapies that maximize remission and minimize corticosteroid dependence in patients with moderate-to-severe CD and UC.

Velayos FS, Sandborn WJ. · Center for Crohn's and Colitis, University of California, San Francisco, 2330 Post Street Suite 610, San Francisco, California 94115, USA. · Curr Gastroenterol Rep. · Pubmed #18377806 No free full text.

Abstract: Over the past decade, the introduction of biologic agents such as tumor necrosis factor-alpha and alpha4 integrin leukocyte adhesion molecule inhibitors has provided new and effective treatment options for patients with inflammatory bowel disease (IBD). Recent debates have centered on where biologics should be positioned within the current treatment strategy so as to maximize efficacy while balancing risk. This review highlights the current position biologics hold relative to conventional therapies within the current "step-up" treatment strategy. It also critically appraises emerging data, testing the hypothesis that positioning biologics early in the IBD treatment algorithm ("top-down" strategy) results in superior outcomes compared with the current step-up strategy, in which biologics are used only in patients failing conventional therapies or who are steroid dependent.

Sandborn WJ. · Division of Gastroenterology and Hepatology, 200 First Street SW, Mayo Clinic, Rochester, MN 55905, USA. · J Clin Gastroenterol. · Pubmed #18277908 No free full text.

Abstract: 5-aminosalicylic acid (5-ASA) is the standard first-line treatment for mild-to-moderate ulcerative colitis. A variety of 5-ASA delivery systems are available and in development, including both oral and rectal formulations; all of which aim to deliver the active drug to the colon while minimizing systemic absorption. Because the efficacy of most oral 5-ASA therapies is broadly similar, the appropriate selection of a given formulation often relies on other factors. This article explores the differences between oral 5-ASA formulations in terms of their delivery system, reviews the available data on oral 5-ASA treatment efficacy and tolerability, and examines the rationale for changing from one 5-ASA formulation to another if a patient does not respond to, or worsens on, their existing agent.

Geboes K, Colombel JF, Greenstein A, Jewell DP, Sandborn WJ, Vatn MH, Warren B, Riddell RH, Anonymous00396. · Department of Pathology, University Hospital Leuven, Belgium. · Inflamm Bowel Dis. · Pubmed #18213696 links to  free full text

Abstract: The precise diagnosis of colitis cannot always be established with the available diagnostic tools. The subgroup of patients with an uncertain diagnosis has been classified as "indeterminate colitis" (IC). The definition of "indeterminate," however, has changed over the years. Originally, IC was proposed by pathologists for colectomy specimens, usually from patients operated on for severe colitis, showing overlapping features of ulcerative colitis (UC) and Crohn's disease (CD). Later, the same terminology was used for patients showing no clear clinical, endoscopic, histologic, and other features allowing a diagnosis of either UC or CD. Therefore, it is difficult to compare different studies. An International Organization of Inflammatory Bowel Diseases (IOIBD) working party confirmed 1) the ambiguous nature of the term, and 2) proposes an updated classification for the category of patients with an unclear diagnosis. According to this, the term IBD unclassified (IBDU) is confirmed, as suggested by the Montreal Working Party 2005 for patients with clinically chronic colitis, that clearly have IBD but when definitive features of CD or UC are absent. In resected specimens the term "colitis of uncertain type or etiology" (CUTE) is preferred. It is accepted that most of the time this may have a prefix, such as severe, chronic. The classification of IBD varies when based only on biopsies rather than on a colectomy specimen. The vast majority of these have severe colitis. For those that cannot bear to abandon the highly ambiguous term IC, if it is used at all, this is where it can be used parenthetically.

Baumgart DC, Sandborn WJ. · Department of Medicine, Division of Gastroenterology and Hepatology, Charité Medical Centre, Virchow Hospital, Medical School of the Humboldt-University of Berlin, 13344 Berlin, Germany. · Lancet. · Pubmed #17499606 No free full text.

Abstract: Crohn's disease and ulcerative colitis are two idiopathic inflammatory bowel disorders. In this paper we discuss the current diagnostic approach, their pathology, natural course, and common complications, the assessment of disease activity, extraintestinal manifestations, and medical and surgical management, and provide diagnostic and therapeutic algorithms. We critically review the evidence for established (5-aminosalicylic acid compounds, corticosteroids, immunomodulators, calcineurin inhibitors) and emerging novel therapies--including biological therapies--directed at cytokines (eg, infliximab, adalimumab, certolizumab pegol) and receptors (eg, visilizumab, abatacept) involved in T-cell activation, selective adhesion molecule blockers (eg, natalizumab, MLN-02, alicaforsen), anti-inflammatory cytokines (eg, interleukin 10), modulation of the intestinal flora (eg, antibiotics, prebiotics, probiotics), leucocyte apheresis and many more monoclonal antibodies, small molecules, recombinant growth factors, and MAP kinase inhibitors targeting various inflammatory cells and pathways. Finally, we summarise the practical aspects of standard therapies including dosing, precautions, and side-effects.

D'Haens G, Sandborn WJ, Feagan BG, Geboes K, Hanauer SB, Irvine EJ, Lémann M, Marteau P, Rutgeerts P, Schölmerich J, Sutherland LR. · University Hospital Gasthuisberg, Leuven, Belgium. · Gastroenterology. · Pubmed #17258735 No free full text.

This publication has no abstract.

Sandborn WJ. · Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA. · Rev Gastroenterol Disord. · Pubmed #16699478 No free full text.

Abstract: Sulfasalazine, olsalazine, balsalazide, delayed-release mesalamine, controlled-release mesalamine, mesalamine pellets, and Multi-Matrix System mesalamine are effective first-line therapies for the treatment of mildly to moderately active ulcerative colitis and for subsequent maintenance of remission. For induction therapy it is unclear if there is a dose response above 1.5 g, and for maintenance therapy existing data do not support a dose response above 1.5 g. Sulfasalazine has more frequent side effects than olsalazine, balsalazide, and mesalamine formulations. Once-daily dosing with multi-matrix system mesalamine 1.2 g tablets may lead to optimal compliance. Mesalamine >/= 1.2 g and sulfasalazine >/= 2 g reduce the risk of colorectal cancer in patients with ulcerative colitis. Drug formulations, efficacy expectations and dose response, toxicity expectations, compliance considerations, and chemoprevention considerations are reviewed.

Pardi DS, Sandborn WJ. · Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. · Aliment Pharmacol Ther. · Pubmed #16611268 No free full text.

Abstract: Pouchitis is the most common complication following proctocolectomy and ileal pouch-anal anastomosis in patients with ulcerative colitis. We aim at discussing relevant information on epidemiology, clinical features, risk factors, diagnostic testing, differential diagnosis and treatment of this idiopathic inflammatory condition. A computerized search of PubMed was performed with the search term 'pouchitis', limited to English papers on humans. This strategy identified 514 references. Relevant articles were selected from this list. In addition, the reference list for each of the selected articles was reviewed to identify any additional references. Pouchitis occurs in up to 60% of patients after ileal pouch-anal anastomosis for ulcerative colitis, and has characteristic clinical, endoscopic and histological features. The most important test for diagnosis is pouch endoscopy with biopsy. Antibiotics remain the mainstay of treatment, and other options are discussed for those patients who are refractory to antibiotic therapy.

Sandborn WJ. · Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA. · Colorectal Dis. · Pubmed #16594957 No free full text.

Abstract: Inflammatory bowel disease (IBD) has been the subject of recent intense research and development. A greater insight into the basic pathological mechanisms of ulcerative colitis (UC) and Crohn's disease (CD) has resulted in the emergence of more sophisticated and effective management options. Additionally, established therapies are attracting renewed interest with novel dosage regimens and new formulations offering improved efficacy whilst maintaining an excellent tolerance profile. High dose 5-aminosalicylic acid (5-ASA) has been a focus for investigation in recent clinical trials. The ASCEND study, which compared a 4.8 g/day dose with a 2.4 g/day dose, demonstrated that high dose mesalazine was significantly superior in achieving treatment success and symptom control, whilst maintaining a comparable tolerance and safety profile. The development of biotechnology agents targeted against tumour necrosis factor (TNF) provides promise of new treatment options in both CD and UC. The efficacy of CDP571, adalimumab and certolizumab have been investigated in CD, and infliximab, which is currently approved as an agent in inflammatory and fistulizing CD, has also been recently investigated in UC. Investigational pipeline molecules such as natalizumab, MLN-02, an anti-interleukin 12 antibody and sargramostim, have also shown encouraging results from early studies and are now undergoing evaluation in large clinical trials.

Sandborn WJ. · Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905, USA. · Inflamm Bowel Dis. · Pubmed #16378006 No free full text.

Abstract: In patients with inflammatory bowel disease (IBD), centrifugation has been attempted to remove leukocyte components from whole blood; however, the use of selective filters has proved to result in more active modification of cellular immunity in that 4 times as many white blood cells are removed, which may result in a greater therapeutic effect. Selective apheresis for treatment of IBD, in particular ulcerative colitis (UC), has been used in Japan and some European countries for several years; pilot studies with Adacolumn, a selective therapeutic granulocyte/monocyte apheresis device, in patients with IBD have recently been completed in the United States with favorable results. Unlike conventional pharmacological treatments, selective apheresis may be associated with a relatively low rate of adverse events. Multiple studies have suggested that selective apheresis may be of benefit as a steroid-sparing treatment. In an unblinded randomized trial in 69 steroid-dependent patients with active UC randomized to selective apheresis with Adacolumn or an increased dose of prednisolone, 83% of patients receiving Adacolumn achieved remission compared with 65% of those receiving an increased dose of prednisolone. In another uncontrolled study of 60 patients with active UC, treatment with Adacolumn selective apheresis enabled nearly 70% of steroid-dependent patients to discontinue prednisolone. An unblinded randomized controlled trial of a different selective apheresis device (Cellsorba) versus high-dose prednisolone in patients with active UC showed a greater therapeutic effect (74%) than high-dose prednisolone (38%) and lower frequency of adverse effects (24% versus 68%).

Egan LJ, Sandborn WJ. · Department of Pharmacology, National University of Ireland, Clinical Science Institute, University College Hospital, Galway, Ireland. · Curr Gastroenterol Rep. · Pubmed #16313879 No free full text.

Abstract: Traditional medications for inflammatory bowel disease are small molecule drugs, most of which were developed for use in other diseases before being found to be efficacious for the treatment of ulcerative colitis or Crohn's disease. Recently, several exciting alternative approaches to the medical treatment of inflammatory bowel disease have been developed. These include biologic, probiotic, and apheresis therapies that offer certain advantages over traditional drug therapy for inflammatory bowel disease. The purpose of this review is to assess the current state of knowledge about novel biologic, probiotic, and apheresis therapies and to analyze how best to incorporate these therapies into evolving management paradigms of inflammatory bowel disease.

Isaacs KL, Lewis JD, Sandborn WJ, Sands BE, Targan SR. · University of North Carolina, Chapel Hill, North Carolina, USA. · Inflamm Bowel Dis. · Pubmed #16254481 No free full text.

Abstract: Inflammatory bowel diseases (IBD) encompass Crohn's disease and ulcerative colitis, which are diseases characterized by chronic intestinal inflammation. IBD is believed to result from predisposing genetic and environmental factors (specific antigens and pathogen-associated molecular patterns) acting on the immunoregulatory system and causing inflammation of the gastrointestinal mucosa. IBD may be the result of an imbalance of effector (proinflammatory) and regulatory T-cell responses. Three scenarios indicative of the outcome of this balance exist in animal models: balanced effector and regulatory T cells resulting in a normal controlled inflammation; overactive effector T cells resulting in inflammation and disease; and an absence of regulatory T cells resulting in uncontrolled inflammation and severe, aggressive disease. The number of products under study for the treatment of IBD has increased from 3 products and 1 target in 1993 to more than 30 products and more than 10 targets in 2005. The number of products under development and continued investigations into the pathogenesis of IBD emphasize the need to expand clinical research efforts in IBD.

Sandborn WJ. · Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA. · Rev Gastroenterol Disord. · Pubmed #15741928 No free full text.

Abstract: Crohn's disease is a T helper type 1 response immune disease characterized by increased production of interleukin-12 tumor necrosis factor-a (TNF-a), and interferon-g. Clinical trials have demonstrated that inhibition of TNF is effective for the treatment of Crohn's disease. Adverse events reported in patients treated with anti-TNF agents include immunogenicity, acute infusion reactions, delayed hypersensitivity-type reactions, autoimmune diseases including drug-induced lupus and demyelination, and infection. This article reviews new concepts in the treatment of Crohn's disease and ulcerative colitis with a variety of anti-TNF biologic therapies: infliximab, adalimumab, CDP870, CDP571, etanercept, and onercept.

Sandborn WJ. · Inflammatory Bowel Disease Clinic, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA. · Rev Gastroenterol Disord. · Pubmed #15580151 No free full text.

Abstract: A variety of serologic tests are emerging that are relevant to the diagnosis and treatment of Crohn's disease and ulcerative colitis. These laboratory tests include: anti-neutrophil cytoplasmic antibody with perinuclear staining (pANCA); anti-Saccharomyces cerevisiae antibody (ASCA); outer membrane porin C (Omp C); and I2 antibody (novel homologue of the bacterial transcription-factor families). The potential roles for serologic testing for inflammatory bowel disease (IBD) include adjunctive diagnostic testing in patients with known IBD, screening testing for IBD in patients with compatible gastrointestinal symptoms, and serving as a marker of unique disease course or prediction of response to specific treatments. This article reviews the use of pANCA, ASCA, I2, and Omp C in patients with IBD.

Loftus CG, Egan LJ, Sandborn WJ. · Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation, Rochester, MN 55905, USA. · Gastroenterol Clin North Am. · Pubmed #15177532 No free full text.

Abstract: In the past decade, immunosuppressive drugs have come to play an integral role in the treatment of patients with inflammatory bowel disease. Cyclosporine, microemulsion cyclosporine, tacrolimus, and mycophenolate mofetil can be considered for the treatment of patients with refractory inflammatory Crohn's disease, fistulizing Crohn's disease, and severe ulcerative colitis. This article reviews the use of cyclosporine, tacrolimus, and mycophenolate mofetil in patients with inflammatory bowel disease, with emphasis on pharmacology, results in controlled clinical trials, and safety, and issues related to dosing and toxicity monitoring.

Sandborn WJ, Yednock TA. · Inflammatory Bowel Disease Clinic, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905, USA. · Am J Gastroenterol. · Pubmed #14638336 No free full text.

Abstract: Crohn's disease involves persistent recruitment of leukocytes into gut tissue, coupled with dysregulated activation of specific immune cell function. Adhesion molecules expressed by circulating leukocytes, such as alpha 4 integrin, mediate their attachment to vascular endothelial cells lining blood vessels within the intestine and facilitate their migration into the tissue. Through interactions with extracellular matrix molecules, adhesion molecules then support immune cell activation and survival within the intestinal wall. Agents that interfere with these adhesive interactions hold great potential for suppressing the cycle of leukocyte infiltration and activation, and thereby, for ameliorating chronic inflammation. This article will discuss clinical data for a humanized monoclonal antibody against alpha 4 integrin, natalizumab, which is the first alpha 4 integrin antagonist in a new class of biotechnology agents referred to as selective adhesion molecule inhibitors.

Sandborn WJ. · Inflammatory Bowel Disease Clinic, Division of Gastroenterology and Hepatology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA. · Best Pract Res Clin Gastroenterol. · Pubmed #12617886 No free full text.

Abstract: Tumour necrosis factor (TNF) plays an important role in mediating the inflammation of inflammatory bowel disease, in particular, Crohn's disease. Strategies aimed at reducing tumour necrosis factor in patients with inflammatory bowel disease include the mouse/human chimeric monoclonal antibody infliximab, the humanized monoclonal antibody CDP571, the human soluble TNF p55 receptor onercept, the human monoclonal antibody D2E7 (adalimumab), the anti-TNF human antibody Fab' fragment-polyethelene glycol (PEG) conjugate CDP870, and the small molecules thalidomide and CNI-1493 (MAP-kinase inhibitor). Infliximab is effective for treating active Crohn's disease, maintaining remission, closing fistulas, maintaining fistula closure, and treating ankylosing spondylitis. Infliximab is also being investigated for the treatment of ulcerative colitis. Side-effects occurring in patients treated with infliximab include human anti-chimeric antibodies, infusion reactions, delayed hypersensitivity reactions, formation of autoantibodies, and, in rare circumstances, drug-induced lupus and serious infections, including tuberculosis. CDP571 is effective for treating active Crohn's disease, steroid sparing, and possibly for closing fistulas and maintaining remission. Side-effects occurring in patients treated with CDP571 include anti-idiotype antibodies, infusion reactions and the formation of autoantibodies. A controlled trial of etanercept in patients with Crohn's disease was negative. Pilot studies with onercept, thalidomide, and CNI-1493 have suggested benefit for Crohn's disease. There are no published data on the efficacy of adalimumab (D2E7) or CDP870 for either Crohn's disease or ulcerative colitis. Anti-tumour necrosis factor therapies are effective for the treatment of Crohn's disease and are being investigated for ulcerative colitis.

Sandborn WJ, Hanauer SB. · Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. · Aliment Pharmacol Ther. · Pubmed #12492730 links to  free full text

Abstract: AIM: : To quantify through systematic review the pharmacokinetic profiles of the oral delayed release and sustained release mesalazine (5-aminosalicylate, 5ASA) formulations (Asacol, Salofalk, Mesasal, Claversal, Pentasa) and pro-drugs (sulfasalazine, olsalazine, balsalazide) used in the management of ulcerative colitis. METHODS: : Selected articles had: (1) adult healthy volunteers or patients with ulcerative colitis and (2) quantification of pharmacokinetic data to include, at a minimum, urinary excretion of total 5ASA [5ASA plus N-Acetyl-5ASA (N-Ac-5ASA)]. DATA COLLECTION AND ANALYSIS: : Pharmacokinetic data (Tmax, Cmax, AUC, urinary excretion, faecal excretion) of 5ASA, its major metabolite N-Acetyl-5ASA, total 5ASA, and the parent pro-drug compounds was extracted. MAIN RESULTS: : The summary results for urinary excretion of total 5ASA over 24-96 h in all subjects (either mean or median) were: sulfasalazine mean 11-33% or median 22%; olsalazine mean 14-31% or median 16-27%; balsalazide mean 12-35% or median 20%; Asacol mean 10-35% or median 18-40%; Pentasa mean 15-53% or median 23-34%; Salofalk, Mesasal and Claversal mean 27-56% or median 31-44%. The summary results for faecal excretion of total 5ASA over 24-96 h in all subjects (either mean or median) were: sulfasalazine mean 23-75% or median 38%; olsalazine mean 47-50% or median 17-36%; balsalazide mean 46% or median 22%; Asacol mean 40-64% or median 20-56%; Pentasa mean 12-51% or median 39-59%; Salofalk, Mesasal and Claversal mean 37-44% or median 23-35%. CONCLUSIONS: : The systemic exposure to 5ASA, as measured by urinary excretion of total 5ASA, and the faecal excretion of total 5ASA is comparable for all oral mesalazine formulations and pro-drugs. Thus, selection of a mesalazine therapy for the treatment of ulcerative colitis should be based on other factors such as efficacy, dose-response, toxicity of the parent compound and its metabolites, compliance issues related to dose forms and dosing schedules, and costs.

Sandborn WJ, Targan SR. · Inflammatory Bowel Disease Clinic, Division of Gastroenterology and Hepatology, Mayo Clinic and Mayo Foundation, 200 First Street SW, Rochester, MN 55905, USA. · Gastroenterology. · Pubmed #12016425 No free full text.

Abstract: Advancing knowledge regarding the biology of chronic inflammation has led to the development of specific biologic therapies that mechanistically target individual inflammatory pathways. Many biologic therapies are being evaluated for the treatment of the chronic inflammatory bowel diseases, Crohn's disease and ulcerative colitis. Biologic compounds proven to be effective for Crohn's disease include monoclonal antibodies to tumor necrosis factor (infliximab and CDP571) and to the leukocyte adhesion molecule alpha4 integrin (natalizumab). Other biologic compounds for which there is insufficient evidence to judge efficacy for inflammatory bowel disease include: p55 tumor necrosis factor binding protein (onercept); interferon alpha; interferon beta-1a; anti-interferon gamma antibody; anti-interleukin 12 antibody; p65 anti-sense oligonucleotide (blocks NF-kappaB); granulocyte colony stimulating factor, and granulocyte macrophage colony stimulating factor; anti-interleukin 2 receptor antibody; epidermal growth factor; keratinocyte growth factor 2 (repifermin); human growth hormone; anti-CD4 antibody; and anti-alpha4beta7 antibody. Biologic therapies that have been proven ineffective for inflammatory bowel disease include: interleukin 10; interleukin 11; anti-sense intercellular adhesion molecule-1; and the tumor necrosis factor receptor fusion protein etanercept. Based on the early successes of infliximab, CDP571 and natalizumab, it seems certain that biologic therapy will play an important role in the future treatment of inflammatory bowel disease.

Yang SK, Loftus EV, Sandborn WJ. · Department of Internal Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea. · Inflamm Bowel Dis. · Pubmed #11515854 No free full text.

Abstract: Studies of Asians in Asia show relatively low incidence rates for ulcerative colitis and Crohn's disease compared with North America and Europe. The prevalence of ulcerative colitis in migrant South Asians in Europe is similar to Europeans, whereas the prevalence of Crohn's disease for migrant South Asians in Europe is decreased compared with Europeans. The prevalence for both ulcerative colitis and Crohn's disease in Japan and Korea is relatively low. There are no obvious differences in age or sex distribution or rates of familial aggregation, and there are no significant differences in the clinical characteristics and natural history of ulcerative colitis and Crohn's disease in Asians compared with other racial groups with inflammatory bowel disease.

Sandborn WJ. · Inflammatory Bowel Disease Clinic, Division of Gastroenterology and Hepatology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA. · Acta Gastroenterol Belg. · Pubmed #11475136 No free full text.

Abstract: Forty percent of patients with severe ulcerative colitis will fail to respond to intravenous corticosteroids. Cyclosporine and other calcineurin inhibitors offer an alternative to colectomy for these patients. Intravenous cyclosporine will induce remission within 14 days in 50-80% of patients who fail intravenous corticosteroids. The long-term response rates for responding patients are 40-60%. Subsequent maintenance therapy with azathioprine or 6-mercaptopurine is recommended at the present time, although the uncontrolled studies underlying this observation have yielded variable results. Toxicity occurs frequently in patients treated with high dose cyclosporine, and there is a small risk of opportunistic infection and death. Pilot studies have suggested that the microemulsion cyclosporine formulation Neoral and tacrolimus may also be of benefit in this patient population. Additional studies to determine the dose response of intravenous cyclosporine, to determine the role of azathioprine for maintenance, and to determine the efficacy of Neoral and tacrolimus are needed.

Sandborn WJ, Faubion WA. · Inflammatory Bowel Disease Clinic, Division of Gastroenterology, Mayo Clinic and Mayo Foundation, 200 First Street SW, Rochester, MN 55905, USA. · Curr Gastroenterol Rep. · Pubmed #11079044 No free full text.

Abstract: Knowledge about the clinical pharmacology of medical therapy of inflammatory bowel disease has incrementally advanced. Small studies with mesalamine have suggested that intestinal mucosal concentrations of mesalamine may predict clinical response to mesalamine therapy. Increased expression of glucocorticoid receptor beta and increased expression of the multidrug resistance drug pump P-glycoprotein 170 have been proposed as markers of drug resistance to glucocorticoids. A baseline determination of thiopurine methyltransferase phenotype or genotype may predict early leukopenia in patients treated with azathioprine or 6- mercaptopurine. Serial measurement of erythrocyte 6-thioguanine nucleotides may be useful in tailoring the dose of these medications. A loading dose of intravenous azathioprine does not accelerate the time to response in patients with steroid-treated Crohn's disease; however, standard azathioprine may work more quickly than previously reported. Methotrexate, 15 to 25 mg/wk, is effective for the treatment of Crohn's disease (active or in remission), and there is no significant difference in the erythrocyte concentrations of methotrexate polyglutamate in patients with inflammatory bowel disease receiving 15 mg, compared with 25 mg, subcutaneously on a weekly basis.

Sandborn WJ, Hanauer SB. · Inflammatory Bowel Disease Clinic, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA. · Inflamm Bowel Dis. · Pubmed #10338381 No free full text.

Abstract: Tumor necrosis factor-alpha (TNFalpha), a proinflammatory cytokine, plays an important role in the pathogenesis of inflammatory bowel disease (IBD). Biotechnology agents including a chimeric monoclonal anti-TNF antibody (infliximab), a humanized monoclonal anti-TNF antibody (CDP571), and a recombinant TNF receptor fusion protein (etanercept) have been used to inhibit TNFalpha activity. Controlled trials have demonstrated efficacy for infliximab in moderately to severely active Crohn's disease (CD) and fistulizing CD sufficient to justify recent U.S. Food and Drug Administration (FDA) approval. Additional trials have been completed in rheumatoid arthritis (RA). Similarly, preliminary controlled trials have suggested efficacy for CDP571 in active CD and RA. Larger controlled trials have demonstrated efficacy for etanercept in RA patients who have failed disease modifying antirheumatic drug (DMARD) therapy leading to FDA approval for RA. Toxicities observed with anti-TNF therapies have included formation of human antichimeric antibodies (HACA) with associated acute and delayed hypersensitivity infusion reactions, human antihuman antibodies (HAHAs), and formation of autoantibodies with rare instances of drug-induced lupus. Several cases of non-Hodgkin's lymphoma also has been described. Future studies should evaluate optimal timing and duration of anti-TNF therapy, the utility of adjuvant medical treatments during anti-TNF therapy, and evaluate long-term safety and efficacy of the various anti-TNF agents.

Sandborn WJ. · Inflammatory Bowel Disease Clinic, Division of Gastroenterology and Hepatology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA. · Am J Gastroenterol. · Pubmed #10235187 No free full text.

Abstract: Smoking is protective against developing ulcerative colitis. Nicotine may be the cause of this protective effect. Controlled trials have demonstrated efficacy of transdermal nicotine for active ulcerative colitis. Side effects observed with transdermal nicotine include contact dermatitis, nausea, and lightheadedness. Topical administration of nicotine to the colon reduces nicotine blood concentrations and side effects, and may be of clinical benefit.