Crohn Disease: Sandborn WJ

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 WJ. · No affiliation provided · Gut. · Pubmed #17303600 No free full text.

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Sandborn WJ, Feagan BG. · No affiliation provided · Gastroenterology. · Pubmed #15362055 No free full text.

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Sandborn WJ. · No affiliation provided · Gastroenterology. · Pubmed #12671907 No free full text.

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Peyrin-Biroulet L, Desreumaux P, Sandborn WJ, Colombel JF. · Hôpital Claude Huriez, Centre Hospitalier Universitaire de Lille, Lille, France. · Lancet. · Pubmed #18603161 No free full text.

Abstract: In the past few years, antagonists of tumour necrosis factor have resulted in unforetold therapeutic benefits in Crohn's disease, but the magnitude and duration of responses are variable. New agents are therefore needed. Their development has benefited from advances in the understanding of the pathophysiology of this disease. Uncontrolled activation of the acquired immune system has an important role, and lymphocytes, cytokines, and adhesion molecules are broadly targeted for therapeutic intervention. With increasing evidence of an implication of the innate immune system and the intestinal epithelium, the therapeutic paradigm is also shifting from mere immunosuppression to the reinforcement of the intestinal barrier. We review mechanisms of actions of new drugs and the efficacy and adverse events from data from clinical trials. We discuss future directions, including new strategies with optimum endpoints.

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.

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.

Sandborn WJ, Feagan BG, Lichtenstein GR. · Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA. · Aliment Pharmacol Ther. · Pubmed #17877506 No free full text.

Abstract: BACKGROUND: Patients with Crohn's disease alternate between periods of active, symptomatic disease and periods of remission. The treatment goal for Crohn's disease is to induce and then maintain remission of symptoms. AIM: To review evidence from randomized, controlled, clinical trials on medical therapies for inducing and maintaining remission in patients with mild-to-moderate Crohn's disease, and to suggest the best evidence-based approaches for induction and maintenance therapies. METHODS: PubMed search using the following terms: sulfasalazine or salicylazosulfapyridine or aminosalicylate or aminosalicylic acid or mesalamine or mesalazine or corticosteroid or prednisone or prednisolone or methylprednisolone or budesonide or antibiotic or metronidazole or ciprofloxacin or immunosuppressive or azathioprine or mercaptopurine or thiopurine or methotrexate and Crohn's disease. RESULTS: Randomized, controlled trials demonstrated that sulfasalazine, budesonide, and conventional corticosteroids are effective for inducing remission of mild-to-moderate Crohn's disease when administered for a period of 8-16 weeks. An ideal maintenance therapy does not currently exist. CONCLUSIONS: Selection of maintenance therapy is based on a combination of evidence from controlled trials and patient features including disease severity and location, co-morbidities, previous response to treatment, and previous surgical resection. The options for maintenance therapy include therapy cessation and patient observation following successful induction, budesonide, or immunosuppressive therapy.

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.

Sandborn WJ. · Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA. · Rev Gastroenterol Disord. · Pubmed #17392636 No free full text.

Abstract: Although infliximab continues to make an important contribution to the management of Crohn's disease, its use includes several clinical challenges, including loss of response, loss of tolerability due to acute and delayed infusion reactions, and the need for intravenous administration by a health care provider. Newer anti-tumor necrosis factor-a agents such as certolizumab pegol and adalimumab have been shown in clinical trials to have similar efficacy as infliximab, without the acute and delayed infusion reactions. Further information is needed about infliximab, certolizumab pegol, and adalimumab so we can understand the relationships among these 3 agents in terms of antibody formation, drug concentration, dosing (episodic vs systematic maintenance), concomitant immunosuppressive therapy, and efficacy.

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.

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.

Mahadevan U, Kane S, Sandborn WJ, Cohen RD, Hanson K, Terdiman JP, Binion DG. · Division of Gastroenterology, Department of Medicine, University of California San Francisco, CA 94115, USA. · Aliment Pharmacol Ther. · Pubmed #15771759 links to  free full text

Abstract: AIM: To study the effects of infliximab on pregnancy and foetal outcome. METHODS: We conducted a retrospective chart review of women with Crohn's disease treated intentionally with infliximab during pregnancy. The primary outcome measure was the occurrence of congenital malformations. Secondary outcome measures were the rate of premature birth, low-birth weight, small for gestational age infants, intrauterine growth retardation and caesarean section. RESULTS: Ten women were identified. Eight women received maintenance infliximab infusions throughout their pregnancy and two women received their initial infliximab infusions during pregnancy. All 10 pregnancies ended in live births. No infants had congenital malformations, intrauterine growth retardation or small for gestational age parameters. Three infants were premature and one had low-birth weight. Eight women had a caesarean section. CONCLUSIONS: This is the first reported series of intentional infliximab use throughout pregnancy. These data, combined with other studies of inadvertent use of infliximab during pregnancy, suggest that the benefits of infliximab in achieving response and maintaining remission in mothers with Crohn's disease may outweigh the risk to the foetus of exposure to the drug. Further prospective data collection will be helpful to confirm these findings.

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 and Mayo Foundation, Rochester, Minnesota, USA. · Rev Gastroenterol Disord. · Pubmed #15583528 No free full text.

Abstract: The chimeric monoclonal antibody to tumor necrosis factor (TNF), infliximab, is an effective therapy for Crohn's disease. However, the formation of human anti-chimeric antibodies to infliximab (immunogenicity) can lead to loss of efficacy as well as acute infusion reactions and delayed hypersensitivity reactions. The fully human monoclonal antibody adalimumab and the pegylated humanized monoclonal antibody fragment CDP870 are biologic therapies against TNF that might be effective for Crohn's disease and less immunogenic than infliximab. Other potential alternatives to infliximab for Crohn's disease include the humanized anti-adhesion molecule antibodies natalizumab and MLN-02, the humanized anti-interleukin 12 antibody ABT-874, the humanized anti-interferon g antibody fontolizumab, the humanized anti-interleukin 6 receptor antibody MRA, and human recombinant granulocyte macrophage colony stimulating factor (sargramostim). Some, or all, of these therapies will likely represent important treatments for Crohn's disease in the future.

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.

Egan LJ, Sandborn WJ. · Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905, USA. · Gastroenterology. · Pubmed #15168368 No free full text.

Abstract: The medical therapy of Crohn's disease has improved considerably in recent years. In large part, this is due to the introduction of new efficacious agents, both "biologics" and traditional small molecules. Further study of older drugs has also advanced our ability to devise the optimum approach to individual Crohn's disease patients by better clarifying the benefits, adverse effects, and means to optimize doses of established medications. In this review, we present an evidence-based approach to the medical management of active Crohn's disease, Crohn's disease in remission, and perianal Crohn's disease that emphasizes recent advances that have come from the results of randomized controlled clinical trials.

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. · Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. · Curr Gastroenterol Rep. · Pubmed #14602060 No free full text.

Abstract: The introduction of infliximab, a mouse/human chimeric monoclonal antibody to tumor necrosis factor (TNF), is an important advance in the treatment of Crohn's disease. Infliximab is effective for induction and maintenance of remission in patients with inflammatory luminal and fistulizing disease. The development of human antichimeric antibodies (HACAs) has led to infusion reactions and loss of efficacy in patients treated with infliximab. Strategies to reduce the frequency of HACA formation include induction of immunologic tolerance with a three-dose regimen at 0, 2, and 6 weeks followed by systematic maintenance dosing every 8 weeks; concomitant immunosuppressive therapy with azathioprine, 6-mercaptopurine, or methotrexate; and premedication with intravenous corticosteroids. Humanized or fully human anti-TNF biotechnologic agents, including CDP571, CDP870, etanercept, adalimumab, and onercept, are theoretically less immunogenic than the chimeric antibody infliximab. Etanercept is not effective for Crohn's disease. CDP571 is not effective in unselected patients with active Crohn's disease, but it may be effective in patients with elevated C-reactive protein. The efficacy of CDP870, adalimumab, and onercept is under investigation. The different mechanisms of action of these anti-TNF agents may account for their variable efficacy. Their benefits, however, must be considered in the context of their risks, including infusion reaction; delayed hypersensitivity-like reaction; new onset of autoimmunity, with rare cases of drug-induced lupus and new-onset demyelination; and the potential for rare but serious infections.

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.

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Sandborn WJ, Feagan BG. · Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA. · Aliment Pharmacol Ther. · Pubmed #12895211 links to  free full text

Abstract: Previously, clinicians have had few choices in treating mild to moderate Crohn's disease. They currently treat these Crohn's disease patients with oral mesalamine and antibiotics. This treatment approach is based on the safety of these agents, and the perception that they are effective. This perception regarding efficacy may be influenced by publication bias. This review examines the efficacy and safety data of the conventional corticosteroids, mesalamine, sulfasalazine, budesonide and antibiotics for inducing the remission of mild to moderate Crohn's disease from randomized controlled trials, and proposes an evidence-based treatment approach. Sulfasalazine has demonstrated modest efficacy when Crohn's disease is confined to the colon. Mesalamine has no clear benefit over placebo in treating active Crohn's disease. Conventional corticosteroids effectively induce remission but are associated with unwanted adverse effects. Budesonide has similar efficacy to conventional steroids with far fewer adverse effects. Antibiotics have not consistently demonstrated efficacy. We propose a new evidence-based approach which suggests inducing remission of mild to moderate Crohn's disease with budesonide 9 mg/day for patients with ileal and/or right colonic involvement; sulfasalazine for those with disease limited to the colon; and conventional steroids for high disease activity, those who failed budesonide and those with left-sided disease who are allergic or intolerant to sulfasalazine.

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.

Feagan BG, Sandborn WJ. · Robart's Research Institute, University of Western Ontario, London, Ontario, Canada. · Rev Gastroenterol Disord. · Pubmed #12478239 No free full text.

Abstract: The initial choice of therapy for mild to moderately active Crohn's disease is controversial. Both the National Cooperative Crohn's Disease Study (NCCDS) and the European Cooperative Crohn's Disease Study (ECCDS) demonstrated that sulfasalazine is effective for the induction of remission. Subsequent studies of new mesalamine formulations showed inconsistent results; two trials, however, demonstrated a statistically significant improvement with Pentasa and Asacol treatment, and meta-analyses suggest a modest benefit of mesalamine maintenance therapy. The NCCDS and ECCDS trials found that corticosteroid therapy is much more effective than sulfasalazine for induction of remission, but corticosteroids did not show maintenance benefits. Corticosteroid use is frequently associated with adverse effects, and the majority of patients treated with prednisone become either steroid-refractory or steroid-dependent; many of these patients ultimately need treatment with immunosuppressives and/or surgery. Budesonide, a topical corticosteroid with high first-pass hepatic metabolism, is slightly less effective in inducing remission than conventional corticosteroids but is significantly less likely to cause side effects. Budesonide 9 mg/day was shown to be more effective than mesalamine (Pentasa 4 g/day) for induction therapy, but budesonide has been ineffective as a maintenance therapy. Mesalamine may be useful for patients with more extensive disease, those intolerant of sulfasalazine, or those with contraindications or intolerance to budesonide. Alternatively, sulfasalazine is effective in the presence of colonic disease. Clinicians must decide on the basis of the existing evidence whether budesonide or mesalamine is the preferred initial therapy for active Crohn's disease.

Kane SV, Schoenfeld P, Sandborn WJ, Tremaine W, Hofer T, Feagan BG. · Section of Digestive Deseases, University of Chicago School of Medicine, Chicago, Ill 60637, USA. · Aliment Pharmacol Ther. · Pubmed #12182751 links to  free full text

Abstract: AIM: To assess the effectiveness and safety of budesonide in comparison to corticosteroids, 5-aminosalicylic acid (5-ASA), or placebo for inducing remission of active Crohn's disease and for maintaining remission. STUDY SELECTION CRITERIA: Randomized controlled trials comparing budesonide to corticosteroids, 5-ASA products or placebo were included. Trials had to report on the effectiveness of treatment (defined as decreasing or maintaining Crohn's Disease Activity Index, CDAI, scores < or = 150) or adverse events. DATA ANALYSIS: After assessing the validity of study design and independent, duplicate data extraction from selected trials, summary relative risks (RR) were calculated for each outcome. A test of heterogeneity was also calculated for each outcome using a random effects model. RESULTS: Budesonide was more likely to induce remission than placebo (RR=1.82, 95% CI: 1.15-2.88) or 5-ASA (RR=1.73, 95% CI: 1.26-2.39), although only one trial compared budesonide to 5-ASA products. Although budesonide induced remission less frequently than conventional corticosteroids (RR=0.87, 95% CI: 0.76-0.995), there was no significant difference between conventional corticosteroids and budesonide for inducing remission among patients with a low disease activity (initial CDAI=200-300). Budesonide was significantly less likely to cause corticosteroid-associated adverse events than conventional corticosteroids (RR=0.65, 95% CI: 0.53-0.80). No significant difference in total adverse events or corticosteroid-associated adverse events was demonstrated between budesonide and 5-ASA or placebo. CONCLUSION: Budesonide is significantly more effective than placebo or 5-ASA for inducing remission of active Crohn's disease. Although budesonide is 13% less effective for the induction of remission in active Crohn's disease than conventional corticosteroids, it is less likely to cause corticosteroid-related adverse effects. Budesonide is ineffective in maintaining remission.