pulmicort and Crohn-Disease

Crohn's Disease (CD) is a chronic inflammatory disease that can lead to progressive damage to the gastrointestinal tract and significant disability. Early, "top-down" biologic therapy is recommended in moderate-to-severe CD to induce remission and to prevent hospitalization and complications. However, an estimated 20-30% of patients with CD have a mild disease course and may not garner sufficient benefit from expensive, immunosuppressing agents to justify their risks. Herein, we review characteristics of patients with mild CD, the available options for disease treatment and monitoring, and future directions of research.. For ambulatory outpatients with low-risk, mild, ileal or ileocolonic CD, induction of remission with budesonide is recommended. For colonic CD, sulfasalazine is a reasonable choice, although other aminosalicylates have no role in the treatment of CD. No large, randomized trial has supported the use of antibiotics or antimycobacterials in the treatment of CD. Partial Enteral Nutrition and Crohn's Disease Exclusion Diets may be appropriate for inducing remission in some adult patients, with trials ongoing. Select patients with mild-to-moderate CD may benefit from maintenance therapy with azathioprines or gut specific biologics, such as vedolizumab. The role of complementary and alternative medicine is not well defined. The identification, risk stratification, and monitoring of patients with mild CD can be a challenging clinical scenario. Some patients with low risk of disease progression may be appropriate for initial induction of remission with budesonide or sulfasalazine, followed by close clinical monitoring. Future research should focus on pre-clinical biomarkers to stratify disease, novel therapies with minimal systemic immune suppression, and validation of rigorous clinical monitoring algorithms.

Topics: Anti-Bacterial Agents; Budesonide; Crohn Disease; Enteral Nutrition; Humans; Remission Induction; Sulfasalazine

The main objectives in Crohn's disease are to avoid disease complications and preserve the patient's quality of life. Early disease control and close monitoring with specific targets to reach might be the only way to change the disease course. In two decades, we have moved from clinical response to full remission (clinical and endoscopic remission) requiring a tight monitoring of both symptoms and objective signs of inflammation. This review summarizes the concepts of tight control and treat-to-target and their potential for disease modification.

Topics: Adalimumab; Adult; Anti-Inflammatory Agents; Biomarkers; Budesonide; Colonoscopy; Crohn Disease; Disease Management; Disease Progression; Female; Gastroenterology; Goals; Humans; Inflammation Mediators; Intestinal Mucosa; Magnetic Resonance Imaging; Patient Reported Outcome Measures; Practice Guidelines as Topic; Prognosis; Quality of Life; Remission Induction; Treatment Outcome

Recently, there have been a few reports of rituximab (RTX)-induced Crohn's disease, but there is no literature available on successful long-term treatment and the clinical outcome of this condition. We retrospectively analyzed the clinical data of a rare case of Crohn's disease induced by RTX administered as induction and prolonged maintenance therapy of a follicular lymphoma, diagnosed synchronously with a gastric signet ring cells carcinoma, treated at our hospital.

Topics: Anti-Inflammatory Agents; Antineoplastic Agents, Immunological; Budesonide; Carcinoma, Signet Ring Cell; Crohn Disease; Drug Therapy, Combination; Humans; Induction Chemotherapy; Lymphoma, Follicular; Maintenance Chemotherapy; Male; Mesalamine; Middle Aged; Neoplasms, Multiple Primary; Rituximab; Stomach Neoplasms; Treatment Outcome

This study aimed to identify factors that affect the prognosis of budesonide therapy for Crohn's disease patients.. Change in Crohn's disease activity index (CDAI) scores at latest follow-up after budesonide therapy reported by individual studies were pooled to gain overall effect size under random effects model and then metaregression analyses were performed to identify factors affecting the change in CDAI scores after budesonide treatment.. Fifteen studies (1875 patients; age, 35.6 years [95% confidence interval (CI): 34.1, 37.0]; 41.66% [95% CI: 37.44, 45.88] males; 33.3% [95% CI: 24.3, 42.3] smokers; weight, 64.7 kg [95% CI: 62.71 66.6] and height, 168 cm [95% CI: 165, 171]) were included. Disease duration was 7.0 years [95% CI: 5.7, 8.2] and duration of the current episode was 3.1 months [95% CI: 1.7, 4.4]. Proportion of patients with prior resection was 42% [95% CI: 34%, 50%]. The disease was 21% in the ileum, 61% in ileocecum, and 18% in the colon. Budesonide dose was 8.83 mg/d [95% CI: 7.52, 10.14]. In a follow-up duration of 21.0 weeks [95% CI: 15.2, 26.8], budesonide treatment was associated with improvement in CDAI score of -117.8 [95% CI: -134.0, -102.0]. The magnitude of the change in CDAI score at the latest follow-up was significantly inversely associated with the percentage of smokers, but positively associated with the baseline CDAI score and duration of the current episode.. Budesonide therapy to Crohn's disease patients appears to be more effective in patients with the more serious condition. Smoking may also affect the prognosis.

Topics: Anti-Inflammatory Agents; Budesonide; Crohn Disease; Humans; Prognosis; Risk Factors; Severity of Illness Index; Smoking

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

Topics: Algorithms; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Glucocorticoids; Humans; Methylprednisolone; Prednisone

Crohn's disease (CD) is a chronic, progressive, and disabling inflammatory bowel disease (IBD) with an uncertain etiopathogenesis. CD can involve any site of the gastrointestinal tract from the mouth to the anus, and is associated with serious complications, such as bowel strictures, perforations, and fistula formation. The incidence and prevalence rates of CD in Korea are still lower compared with those in Western countries, but they have been rapidly increasing during the recent decades. Although there are no definitive curative modalities for CD, various medical and surgical therapies have been applied for the treatment of this disease. Concerning CD management, there have been substantial discrepancies among clinicians according to their personal experience and preference. To suggest recommendable approaches to the diverse problems of CD and to minimize the variations in treatment among physicians, guidelines for the management of CD were first published in 2012 by the IBD Study Group of the Korean Association for the Study of the Intestinal Diseases. These are the revised guidelines based on updated evidence, accumulated since 2012. These guidelines were developed by using mainly adaptation methods, and encompass induction and maintenance treatment of CD, treatment based on disease location, treatment of CD complications, including stricture and fistula, surgical treatment, and prevention of postoperative recurrence. These are the second Korean guidelines for the management of CD and will be continuously revised as new evidence is collected.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Crohn Disease; Humans; Infliximab; Mercaptopurine; Mesalamine; Methotrexate; Prednisolone; Severity of Illness Index; Tumor Necrosis Factor-alpha

Induction treatment of mild-to-moderate Crohn's disease is controversial.. To compare the induction of remission between different doses of mesalamine, sulfasalazine, corticosteroids, and budesonide for active Crohn's disease.. We identified randomized controlled trials from existing Cochrane reviews and an updated literature search in Medline, EMBASE, and CENTRAL to November 2015.. We included randomized controlled trials (n = 22) in adult patients with Crohn's disease that compared budesonide, sulfasalazine, mesalamine, or corticosteroids with placebo or each other, for the induction of remission (8-17 wks). Mesalamine (above and below 2.4 g/d) and budesonide (above and below 6 mg/d) were stratified into low and high doses.. Our primary outcome was remission, defined as a Crohn's Disease Activity Index score <150. A Bayesian random-effects network meta-analysis was performed on the proportion in remission.. Corticosteroids (odds ratio [OR] = 3.80; 95% credible interval [CrI]: 2.48-5.66), high-dose budesonide (OR = 2.96; 95% CrI: 2.06-4.30), and high-dose mesalamine (OR = 2.29; 95% CrI: 1.58-3.33) were superior to placebo. Corticosteroids were similar to high-dose budesonide (OR = 1.21; 95% CrI: 0.84-1.76), but more effective than high-dose mesalamine (OR = 1.83; 95% CrI: 1.16-2.88). Sulfasalazine was not significantly superior to any therapy including placebo.. Randomized controlled trials that use a strict definition of induction of remission and disease severity at enrollment to assess effectiveness in treating mild-to-moderate Crohn's disease are limited.. Corticosteroids and high-dose budesonide were effective treatments for inducing remission in mild-to-moderate Crohn's disease. High-dose mesalamine is an option among patients preferring to avoid steroids.

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Bayes Theorem; Budesonide; Comparative Effectiveness Research; Crohn Disease; Humans; Induction Chemotherapy; Mesalamine; Network Meta-Analysis; Odds Ratio; Randomized Controlled Trials as Topic; Sulfasalazine; Treatment Outcome

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.. 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.. 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.. 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 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.. 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 contr. 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.

Topics: Aminosalicylic Acids; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Crohn Disease; Delayed-Action Preparations; Gastrointestinal Agents; Humans; Induction Chemotherapy; Mesalamine; Randomized Controlled Trials as Topic; Sulfasalazine

Mild Crohn's disease (CD) is classified as those patients who are ambulatory, with <10 % weight loss, are eating and drinking without abdominal mass, tenderness, obstructive symptoms, or fever, and endoscopically they have non-progressive mild findings. Initial evaluation of mild CD should focus on assessment for high-risk features requiring more aggressive therapy. In contrast to moderate-to-severe disease, where therapy is focused on mucosal healing, the management of mild CD is focused on symptom management, while exposing the individual to minimal therapeutic risks. Budesonide is the most commonly used medication for mild CD given its safety profile. Assessment of inflammatory markers, in concert with computed-tomography (CT) or magnetic resonance (MR) enterographies and endoscopic studies, should be considered in clinical remission to ensure that mucosal inflammation is not present. Endoscopic inflammation can precede clinical recurrence. Individuals with mild CD require routine vaccination, monitoring for iron-deficiency anemia and vitamin D deficiency, and colorectal cancer screening when appropriate.

Topics: Budesonide; Crohn Disease; Disease Progression; Gastrointestinal Agents; Glucocorticoids; Humans; Population Surveillance; Prognosis; Risk Factors; Severity of Illness Index

Budesonide and mesalazine (mesalamine) are commonly used in the medical management of patients with mild to moderate Crohn's disease.. To assess their comparative efficacy and harm using the methodology of network meta-analysis.. A comprehensive search of Medline, Embase, the Cochrane Library and ClinicalTrials.gov, through October 2014, was performed to identify randomised controlled trials (RCTs) that recruited adult patients with active or quiescent Crohn's disease, and compared budesonide or mesalazine with placebo, or against each other, or different dosing strategies of one drug.. Twenty-five RCTs were combined using Bayesian network meta-analysis. Budesonide 9 mg/day, or at higher doses (15 or 18 mg/day), was shown superior to placebo for induction of remission [odds ratio (OR), 2.93; 95% credible interval (CrI), 1.52-5.39, and OR, 3.28; CrI, 1.46-7.55 respectively] and ranks at the top of the hierarchy of the competing treatments. For maintenance of remission, budesonide 6 mg/day demonstrated superiority over placebo (OR, 1.69; CrI, 1.05-2.75), being also at the best ranking position among all compared treatment strategies. No other comparisons (i.e. different doses of mesalazine vs. placebo or budesonide, for induction or maintenance of remission) reached significance. The occurrence of withdrawals due to adverse events was not shown different between budesonide, mesalazine and placebo, in both the induction and maintenance phases.. Budesonide, at the doses of 9 mg/day, or higher, for induction of remission in active mild or moderate Crohn's disease, and at 6 mg/day for maintenance of remission, appears to be the best treatment choice.

Topics: Adult; Bayes Theorem; Budesonide; Crohn Disease; Humans; Mesalamine; Odds Ratio; Randomized Controlled Trials as Topic

Corticosteroids are commonly used for the induction of remission in Crohn's disease. However, traditional corticosteroids can cause significant adverse events. Budesonide is an alternative glucocorticoid with limited systemic bioavailability.. The primary objective was to evaluate the efficacy and safety of oral budesonide for the induction of remission in Crohn's disease.. The following electronic databases were searched up to June 2014: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane IBD/FBD Group Specialised Trial Register, and ClinicalTrials.gov. Reference lists of articles, as well as conference proceedings were manually searched.. Randomised controlled trials comparing budesonide to a placebo or active comparator were considered for inclusion.. Two independent investigators reviewed studies for eligibility, extracted the data and assessed study quality. Methodological quality was assessed using the Cochrane risk of bias tool The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. Meta-analysis was performed using RevMan 5.3.5 software. The primary outcome was induction of remission (defined by a Crohn's disease activity index (CDAI) < 150) by week 8 to 16 of treatment. Secondary outcomes included: time to remission, mean change in CDAI, clinical, histological or endoscopic improvement, improvement in quality of life, adverse events and early withdrawal. We calculated the relative risk (RR) and corresponding 95% confidence intervals (CIs) for each dichotomous outcome and the mean difference and corresponding 95% CI for each continuous outcome. Data were analyzed on an intention-to-treat basis. A random-effects model was used for the pooled analyses. The overall quality of the evidence supporting the primary outcomes and selected secondary outcomes was evaluated using the GRADE criteria.. Fourteen studies (1805 patients) were included: Nine (779 patients) compared budesonide to conventional corticosteroids, three (535 patients) were placebo-controlled, and two (491 patients) compared budesonide to mesalamine. Ten studies were judged to be at low risk of bias. Three studies were judged to be at high risk of bias due to open label design. One study was judged to be at high risk of bias due to selective reporting. After eight weeks of treatment, 9 mg budesonide was significantly more effective than placebo for induction of clinical remission. Forty-seven per cent (115/246) of budesonide patients achieved remission at 8 weeks compared to 22% (29/133) of placebo patients (RR 1.93, 95% CI 1.37 to 2.73; 3 studies, 379 patients). A GRADE analysis indicated that the overall quality of the evidence for this outcome was moderate due to sparse data (144 events). Budesonide was significantly less effective than conventional steroids for induction of remission at eight weeks. Fifty-two per cent of budesonide patients achieved remission at week 8 compared to 61% of patients who received conventional steroids (RR 0.85, 95% CI 0.75 to 0.97; 8 studies, 750 patients). A GRADE analysis indicated that the overall quality of the evidence for this outcome was moderate due to risk of bias. Budesonide was significantly less effective than conventional steroids among patients with severe disease (CDAI > 300) (RR 0.52, 95% CI 0.28 to 0.95). Studies comparing budesonide to mesalamine were not pooled due to heterogeneity (I(2) = 81%). One study (n = 182) found budesonide to be superior to mesalamine for induction of remission at 8 weeks. Sixty-eight per cent (63/93) of budesonide patients were in remission at 8 weeks compared to 42% (37/89) of mesalamine patients (RR 1.63, 95% CI 1.23 to 2.16). The other study found no statistically significant difference in remission rates at eight weeks. Sixty-nine per cent (107/154) of budesonide patients were in remission at 8 weeks compared to 62% (132/242) of mesalamine patients (RR 1.12, 95% CI 0.95 to 1.32). Fewer adverse events occurred in those treated with budesonide compared to conventional steroids (RR 0.64, 95% CI 0.54 to 0.76) and budesonide was better than conventional steroids in preserving adrenal function (RR for abnormal ACTH test 0.65, 95% CI 0.55 to 0.78).. Budesonide is more effective than placebo for induction of remission in Crohn's disease. Although short-term efficacy with budesonide is less than with conventional steroids, particularly in those with severe disease or more extensive colonic involvement, the likelihood of adverse events and adrenal suppression with budesonide is lower. The current evidence does not allow for a firm conclusion on the relative efficacy of budesonide compared to 5-ASA products.

Topics: Administration, Oral; Adrenal Cortex Hormones; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Crohn Disease; Humans; Induction Chemotherapy; Mesalamine; Randomized Controlled Trials as Topic

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

Topics: Anti-Inflammatory Agents; Azathioprine; Budesonide; Colitis, Ulcerative; Congresses as Topic; Crohn Disease; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Maintenance Chemotherapy; Mesalamine; Methotrexate; Review Literature as Topic; Secondary Prevention

The incidence and prevalence of Crohn's disease are increasing, particularly in the Western world and Asia. Corticosteroids have been used for decades to treat active Crohn's disease and remain the mainstay in the management of moderate-to-severe relapses in Crohn's disease. The use of corticosteroids, despite their efficacy, may be associated with several drawbacks. This review article provides a comprehensive account of the role of corticosteroids in inducing remission in adult patients with Crohn's disease, including aspects such as approaches to corticosteroid sparing and to minimize the risk of corticosteroid dependency, as well as the role of newer corticosteroids such as budesonide in reducing systemic adverse effects.

Topics: Adrenal Cortex Hormones; Azathioprine; Budesonide; Clinical Trials as Topic; Crohn Disease; Humans; Mercaptopurine; Mesalamine; Tumor Necrosis Factor-alpha

Corticosteroids are effective for induction, but not maintenance of remission in Crohn's disease. Significant concerns exist regarding the risk for adverse events, particularly when corticosteroids are used for long treatment courses. Budesonide is a glucocorticoid with limited systemic bioavailability due to extensive first-pass hepatic metabolism and is effective for induction of remission in Crohn's disease.. To evaluate the efficacy and safety of oral budesonide for maintenance of remission in Crohn's disease.. The following databases were searched from inception to 12 June 2014: PubMed, MEDLINE, EMBASE, CENTRAL, the Cochrane IBD/FBD Group Specialised Trial Register, and ClinicalTrials.gov. Reference lists of articles, as well as conference proceedings were manually searched.. Randomized controlled trials comparing budesonide to a control treatment, or comparing two doses of budesonide, were included. The study population included patients of any age with quiescent Crohn's disease.. Two independent investigators reviewed studies for eligibility, extracted data and assessed study quality using the Cochrane risk of bias tool. The primary outcome was maintenance of remission at various reported follow-up times during the study. Secondary outcomes included: time to relapse, mean change in CDAI, clinical, histological, improvement in quality of life, adverse events and study withdrawal. We calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI) for dichotomous outcomes and the mean difference (MD) and 95% CI for continuous outcomes. Data were analysed on an intention-to-treat basis. The Chi(2) and I(2) statistics were used to assess heterogeneity. Random-effects models were used to allow for expected clinical and statistical heterogeneity. The overall quality of the evidence supporting the primary outcome was assessed using the GRADE criteria.. Twelve studies (n = 1273 patients) were included in the review: eight studies compared budesonide to placebo, one compared budesonide to 5-aminosalicylates, one compared budesonide to traditional systemic corticosteroids, one compared budesonide to azathioprine, and one compared two doses of budesonide. Nine studies used a controlled ileal release form of budesonide, while three used a pH-modified release formulation. Nine studies were judged to be at low risk of bias. Three studies were judged to be at high risk of bias due to blinding and one of these studies also had inadequate allocation concealment. Budesonide 6 mg daily was no more effective than placebo for maintenance of remission at 3 months, 6 months or 12 months. At three months 64% of budesonide 6 mg patients remained in remission compared to 52% of placebo patients (RR 1.25, 95% CI 1.00 to 1.58; 6 studies, 540 patients). A GRADE analysis indicated that the overall quality of the evidence for this outcome was low due to moderate heterogeneity (I(2) = 56%) and sparse data (315 events). At six months 61% of budesonide 6 mg patients remained in remission compared to 52% of placebo patients (RR 1.15, 95% CI 0.95 to 1.39; 5 studies, 420 patients). A GRADE analysis indicated that the overall quality of the evidence for this outcome was moderate due to sparse data (238 events). At 12 months 55% of budesonide 6 mg patients remained in remission compared to 48% of placebo patients (RR 1.13; 95% CI 0.94 to 1.35; 5 studies, 420 patients). A GRADE analysis indicated that the overall quality of the evidence for this outcome was moderate due to sparse data (215 events). Similarly, there was no significant benefit for budesonide 3 mg compared to placebo at 6 and 12 months. There was no statistically significant difference in continued remission at 12 months between budesonide and weaning doses of prednisolone (RR 0.79; 95% CI 0.55 to 1.13; 1 study, 90 patients). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was low due to sparse data (51 events) and high risk of bias (no blinding). Budesonide 6 mg was better than mesalamine 3 g/day at 12 months (RR 2.51, 95% CI 1.03 to 6.12; 1 study, 57 patients). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was very low due to very sparse data (18 events) and high risk of bias (no blinding). There was no statistically significant difference in continued remission at 12 months betwee. These data suggest budesonide is not effective for maintenance of remission in CD, particularly when used beyond three months following induction of remission. Budesonide does have minor benefits in terms of lower CDAI scores and longer time to relapse of disease. However, these benefits are offset by higher treatment-related adverse event rates and more frequent adrenocorticoid suppression in patients receiving budesonide.

Topics: Administration, Oral; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Humans; Induction Chemotherapy; Maintenance Chemotherapy; Randomized Controlled Trials as Topic; Risk; Secondary Prevention

Topics: Administration, Oral; Administration, Topical; Algorithms; Anti-Inflammatory Agents; Budesonide; Cecum; Crohn Disease; Endoscopy, Gastrointestinal; Humans; Ileum; Immunosuppressive Agents; Methotrexate; Prednisolone; Secondary Prevention; Tumor Necrosis Factor-alpha

Surgery is an almost inevitable event in Crohn's disease but is not curative; post-operative recurrence follows a sequential and predictable course. Prevention of post-operative recurrence in Crohn's disease is therefore a relevant problem in the management of the disease. Several drugs have been evaluated to decrease the risk of recurrence: these include mesalazine, antibiotics, probiotics, budesonide, thiopurines and biologic agents. This review focuses on the randomised controlled trials and meta-analyses addressing different drugs and strategies for preventing post-operative recurrence in Crohn's disease.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Antibodies, Monoclonal; Antirheumatic Agents; Budesonide; Combined Modality Therapy; Crohn Disease; Drug Therapy, Combination; Endoscopy, Digestive System; Humans; Immunosuppressive Agents; Infliximab; Interleukin-10; Lactobacillus; Mesalamine; Meta-Analysis as Topic; Multicenter Studies as Topic; Probiotics; Randomized Controlled Trials as Topic; Secondary Prevention; Treatment Outcome

The drugs available for inflammatory bowel disease are aminosalicylates, antibiotics, steroids, immunosuppressors and biologics. The effectiveness of these drugs has been evaluated in many randomized clinical trials, mainly versus placebo. Few studies have been conducted comparing the different drugs among themselves, owing to the methodological problems raised by comparative trials, such as sample size and blindness. This review focuses mainly on the randomized clinical trials that have compared different treatments. Of course comparisons are mainly between drugs used in a particular setting (mild, moderate and severe disease). However, on many occasions there is no homogeneity in these clinical settings, and therefore the results are difficult to interpret.

Topics: Adrenal Cortex Hormones; Aminosalicylic Acids; Anti-Bacterial Agents; Azathioprine; Biological Factors; Budesonide; Crohn Disease; Humans; Intestinal Fistula; Methotrexate; Probiotics; Randomized Controlled Trials as Topic; Secondary Prevention

IBD is a chronic and relapsing inflammatory disorder of the gut that demands long-lasting treatment targeting both flare-up periods and maintenance of remission. Oral systemic steroids have been used to induce remission in patients with active IBD for over 50 years due to their potent anti-inflammatory effects. The efficacy of systemic steroids in this setting has been largely demonstrated. However, the wide range of adverse events associated with these drugs has prompted the development of equally effective but less toxic steroid compounds. Currently, topically acting oral steroids are an important therapeutic option for Crohn's disease, ulcerative colitis and microscopic colitis, being oral budesonide and oral beclomethasone established elements of the IBD armamentarium. At present, oral budesonide is the first-line therapy to induce remission in microscopic colitis and mild to moderate ileocaecal CD patients and oral beclomethasone is effective treating mild to moderate UC patients with left-sided or extensive disease. This review aims at evaluating the current role of these compounds in IBD clinical practice.

Topics: Administration, Oral; Anti-Inflammatory Agents; Beclomethasone; Budesonide; Colitis, Microscopic; Colitis, Ulcerative; Crohn Disease; Humans; Induction Chemotherapy; Inflammatory Bowel Diseases; Maintenance Chemotherapy

Crohn's disease and ulcerative colitis are inflammatory bowel diseases characterised by a chronic relapsing course. Corticosteroids represent the mainstay of medical treatment of inflammatory bowel disease for the induction of remission. Despite the high efficacy of systemic steroids, their use is limited by the high incidence of potentially serious adverse effects. The topically acting steroids are synthetic compounds characterised by high anti-inflammatory activity and low systemic effects by virtue of efficient first-pass hepatic inactivation. Budesonide and Beclomethasone Dipropionate are the two most studied topically acting steroids in inflammatory bowel disease. Oral Budesonide has been extensively studied in the treatment of mild to moderate ileo-caecal Crohn's disease but few data are available concerning oral Beclomethasone Dipropionate. This review focuses on the available evidence of efficacy and safety of oral Beclomethasone Dipropionate in the management of ulcerative colitis and Crohn's disease and a possible role of this steroid in clinical practice is suggested.

Topics: Administration, Oral; Beclomethasone; Budesonide; Colitis, Ulcerative; Crohn Disease; Glucocorticoids; Humans

Many trials focused on the treatment of active luminal Crohn's disease (CD) have been published in literature. A critical reevaluation of the main trials regarding the use of 5-ASA derivates has shown a not significant benefit of such molecules in treating CD and, as a consequence, the European Crohn's and Colitis Organization's (ECCO) therapeutic statements highlight that 5-ASA should be considered clinically no more effective than placebo for active disease. The main evidence regarding the efficacy of conventional steroids as inductive therapy in active CD is still based on the old but fundamental Cooperative studies which can be considered at low risk for biases in spite of the date of publication. Most probably these RCTs will remain unsurpassed. Current data do not support the use of antibiotics for active luminal CD as primary therapeutic strategy in view of very conflicting results. In accordance with these conclusions current guidelines dot not suggest this kind of treatment in active CD. Even if frequently used, data about the role of conventional immunosuppressors for the therapy of active luminal CD ara scanty. Azathioprine/6-MP should be no more considered as remission-inductive agents for active CD while methotrexate could be considered an effective therapeutic option in inducing remission in this setting particular setting. A number of clinical trials are available about the use of anti-TNF alpha agents (infliximab, adalimumab) in active luminal CD. Both drugs are surely effective in inducing remission even if safety and economic concerns should be better considered and investigated.

Topics: Anti-Bacterial Agents; Budesonide; Crohn Disease; Glucocorticoids; Humans; Immunosuppressive Agents; Randomized Controlled Trials as Topic; Salicylates

Maintenance of medically induced remission is a clinical challenge in Crohn's disease (CD), since it is a chronic disease and that often occurs in young people. The introduction of immunosuppressors and biologics has significantly improved the management of these patients, however efficacy and safety of these treatments in the very long term still needs clarification. Furthermore, scientific research is driven more into new drugs to induce remission rather then maintenance.

Topics: Adalimumab; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Budesonide; Crohn Disease; Humans; Immunosuppressive Agents; Infliximab; Methotrexate; Randomized Controlled Trials as Topic; Remission Induction; Salicylates

The use of glucocorticosteroids to treat both Crohn's disease (CD) and ulcerative colitis (UC) is widespread, but no systematic review and meta-analysis has examined the issue of efficacy of these agents in its entirety.. MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through December 2010). Randomized controlled trials (RCTs) recruiting adults with active or quiescent CD comparing standard glucocorticosteroids or budesonide with placebo or each other, or comparing standard glucocorticosteroids with placebo in active UC, were eligible. Dichotomous data were extracted to obtain relative risk (RR) of failure to achieve remission in active disease, and RR of relapse of activity in quiescent disease, with a 95% confidence interval (CI). Adverse events data were extracted where reported.. The search identified 3,061 citations, and 20 trials were eligible. Only one trial was at low risk of bias. Standard glucocorticosteroids were superior to placebo for UC remission (RR of no remission=0.65; 95% CI 0.45-0.93). Both trials of standard glucocorticosteroids in CD remission reported a statistically significant effect, but because of heterogeneity between studies, the overall effect was not significant (RR=0.46; 95% CI 0.17-1.28). Budesonide was superior to placebo for CD remission (RR=0.73; 95% CI 0.63-0.84), but not in preventing CD relapse (RR=0.93; 95% CI 0.83-1.04). Standard glucocorticosteroids were superior to budesonide for CD remission (RR=0.82; 95% CI 0.68-0.98), but glucocorticosteroid-related adverse events were commoner (RR=1.64; 95% CI 1.34-2.00).. Standard glucocorticosteroids are probably effective in inducing remission in UC, and may be of benefit in CD. Budesonide induces remission in active CD, but is less effective than standard glucocorticosteroids, and is of no benefit in preventing CD relapse.

Topics: Anti-Inflammatory Agents; Budesonide; Colitis, Ulcerative; Crohn Disease; Glucocorticoids; Humans; Randomized Controlled Trials as Topic; Remission Induction; Risk; Secondary Prevention; Treatment Failure; Treatment Outcome

Crohn's disease (CD) is a chronic inflammatory disorder characterized by focal, asymmetric, transmural inflammation of any part of the luminal gastrointestinal tract of uncertain etiology and an unpredictable course. The available treatment options include aminosalicylates, budesonide and systemic corticosteroids, antibiotics, immunomodulators,methotrexate and anti-TNF agents. This review discusses recent developments in the treatment of CD and provides a comprehensive update on management of patients with CD based on the data from randomized controlled trials.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal, Humanized; Budesonide; Crohn Disease; Humans; Immunologic Factors; Immunosuppressive Agents; Mesalamine; Methotrexate; Natalizumab; Sulfasalazine; Tumor Necrosis Factor-alpha

Crohn's disease (CD) is a chronic inflammatory disease of the digestive tract with systemic manifestations. Etiology is unknown, even if immunological, genetic and environmental factors are involved. The majority of CD patients require surgery during their lifetime due to progressive bowel damage, but, even when all macroscopic lesions have been removed by surgery, the disease recurs in most cases. Postoperative management represents therefore a crucial mean for preventing recurrence. Several drugs and approaches have been proposed to achieve this aim. Endoscopic inspection of the ileocolic anastomosis within 1 year from surgery is widely encouraged, given that endoscopic recurrence is one of the greatest predictors for clinical recurrence. A strategy should be planned only after stratifying patients according to their individual risk of recurrence, avoiding unnecessary therapies when possible benefits are reduced, and selecting high-risk patients for more aggressive intervention.

Topics: Anastomosis, Surgical; Anti-Bacterial Agents; Budesonide; Crohn Disease; Endoscopy; Gastroenterology; Humans; Inflammation; Mesalamine; Postoperative Period; Recurrence; Risk; Risk Factors; Treatment Outcome

The medical approach to Crohn's disease has been modified in recent years thanks to the introduction of new therapies, like biologics. Also, well-designed studies and systematic reviews have allowed better evaluation of the role of old drugs like steroids and immunosuppressors. This review aims to evaluate the recent evidence on the medical approach to Crohn's disease in the different settings of the disease.. Randomized controlled trials and meta-analyses were included in the review. The research on all the studies discussed was based on the Cochrane Library, Medline and Embase, using the following medical subject headings: Crohn's disease, clinical trial, therapy, 5-aminosalicylic acid, steroid, budesonide, immunosuppressant, anti-meta-analysis TNF and biologics.. In a mild active inflammatory ileocecal disease, budesonide is considered the best approach. The efficacy of aminosalicylates is limited, but a trial that has recently compared aminosalicylates and budesonide has shown that the two drugs are comparable. In a mild colonic disease, sulfasalazine, antibiotics and steroids are effective but the evidence for antibiotics is less clear. The maintenance of remission in this setting is debatable, but sulfasalazine seems the better choice. In a moderate severe ileal and colonic disease, steroids are the best therapy to induce remission. Once remission is reached, immunosuppressors remain today the better choice to maintain the remission. Anti-TNF therapy is indicated in patients intolerant or not responding to steroids and immunosuppressors and in fistulizing Crohn's disease. Early therapy with biologics may be considered in patients with severe disease.

Topics: Adrenal Cortex Hormones; Aminosalicylic Acids; Anti-Bacterial Agents; Anti-Inflammatory Agents; Biological Products; Bone Marrow Transplantation; Budesonide; Crohn Disease; Humans; Immunosuppressive Agents; Intestines; Methotrexate; Purines; Remission Induction; Treatment Outcome; Tumor Necrosis Factor-alpha

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.. 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.. 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).. 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 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.. 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.. 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.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Crohn Disease; Humans; Mesalamine; Randomized Controlled Trials as Topic; Remission Induction; Sulfasalazine

Corticosteroids have been shown to be effective for induction, but not maintenance of remission in Crohn's disease. However, significant concerns exist regarding their risk for adverse events, particularly when used for long treatment courses. Budesonide is a glucocorticoid with limited systemic bioavailability due to extensive first-pass hepatic metabolism. Budesonide has been shown to be effective for induction of remission in Crohn's disease.. To evaluate the efficacy and safety of oral budesonide for maintenance of remission in Crohn's disease.. The following electronic databases were searched: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane IBD/FBD Group Specialised Trial Register, and ClinicalTrials.gov. Reference lists of articles, as well as conference proceedings were manually searched. Study authors, study sponsors and pharmaceutical companies were also contacted.. Randomized controlled trials comparing budesonide to a control treatment, or comparing two doses of budesonide, were included. The study population included patients of any age with Crohn's disease in remission. The primary outcome was maintenance of remission at various reported follow-up times during the study, up to 12 months following enrollment. Secondary outcomes included: time to relapse, mean change in CDAI, clinical, histological or endoscopic improvement, improvement in quality of life, adverse events and study withdrawal.. Two independent investigators reviewed studies for eligibility, extracted the data and assessed study quality using Jadad's criteria. A random or fixed effects model was chosen based on an assessment of heterogeneity, and studies were weighted using the DerSimonian & Laird or the Mantel-Haenszel method accordingly. Meta-analysis was performed using RevMan 4.2.10 software.. Eleven studies were included in the review: 8 studies compared budesonide with placebo, one compared budesonide to 5-aminosalicylates, one compared budesonide to traditional systemic corticosteroids, and one compared two doses of budesonide with no control group. Eight studies used a controlled ileal release form of budesonide, while three used a pH-modified release formulation. Budesonide 6 mg daily was no more effective than placebo for maintenance of remission at 3 months (RR 1.25; 95% CI 1.00 to 1.58; P = 0.05), 6 months (RR 1.15; 95% CI 0.95 to 1.39; P = 0.14), or 12 months (RR 1.13; 95% CI 0.94 to 1.35; P = 0.19). Budesonide was not more effective than weaning doses of prednisolone for maintenance of remission at 12 months (RR 0.79; 95% CI 0.55 to 1.13; P = 0.20), but was better than mesalamine 3 grams per day (RR of remission 2.51; 95% CI 1.03 to 6.12; P = 0.04). Budesonide 3 mg daily was more effective than placebo at 3 months (RR 1.31; 95% CI 1.03 to 1.67; P = 0.03). This benefit was not sustained at 6 months (RR 1.10; 95% CI 0.81 to 1.50; P = 0.53), or 12 months (RR 1.04; 95% CI 0.84 to 1.30; P = 0.70). No differences in efficacy were detected based on the different formulations of budesonide, methods used to induce remission, or budesonide dose. The use of budesonide 6 mg resulted in slight improvements in CDAI scores when assessed at 6 months (WMD -24.3; 95% CI -46.31 to -2.29; P = 0.03) and 12 months (WMD -23.49; 95% CI -46.65 to -0.32; P = 0.05) and mean time to relapse of disease (WMD 59.93 days; 95% CI 19.02 to 100.84; P = 0.004). Adverse events were more frequent in patients treated with 6 mg of budesonide compared with placebo (RR 1.49; 95% CI 1.01 to 2.19; P = 0.05), but not in patients using lower doses of budesonide. These events were relatively minor and did not result in increased rates of study withdrawal. Abnormal adrenocorticoid stimulation tests were seen more frequently in patients receiving both 6 mg daily (RR 2.88; 95% CI 1.72 to 4.82; P < 0.0001) and 3 mg daily (RR 2.73; 95% CI 1.34 to 5.57; P = 0.006) compared with placebo.. Budesonide is not more effective than placebo or weaning prednisolone for maintenance of remission in Crohn's disease. Some modest benefits are noted in patients receiving budesonide compared with placebo in terms of lower CDAI scores and longer time to relapse of disease. However, these benefits are offset by higher treatment-related adverse event rates and more frequent adrenocorticoid suppression in patients receiving budesonide. Therefore, budesonide is not recommended for maintenance of remission in Crohn's disease.

Topics: Administration, Oral; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Humans; Randomized Controlled Trials as Topic; Recurrence; Remission Induction; Risk

Crohn's disease is characterized by recurrent transmural inflammation of the gastrointestinal tract, most commonly, the terminal ileum and the colon. Therapy is aimed at breaking the cycle of inflammation by inducing and maintaining remission. Current effective therapies include systemic corticosteroids, but this class of drugs is associated with a variety of adverse effects, which may lead to significant morbidity and even mortality. Budesonide, a potent corticosteroid designed to have location specific delivery to the gastrointestinal tract, has limited systemic bioavailability largely due to its extensive first pass metabolism and has been demonstrated to be a safer alternative to conventional corticosteroids and of proven efficacy in the induction of remission in mild to moderate Crohn's disease. However, budesonide is not effective in maintaining remission in patients with Crohn's disease.

Topics: Anti-Inflammatory Agents; Budesonide; Crohn Disease; Humans

Topics: Adolescent; Adult; Age Factors; Aged; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Azathioprine; Budesonide; Child; Colitis, Ulcerative; Colorectal Neoplasms; Crohn Disease; Enteral Nutrition; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Mesalamine; Meta-Analysis as Topic; Middle Aged; Prednisone; Pregnancy; Randomized Controlled Trials as Topic; Risk Factors

Corticosteroids play a key role in the induction of remission in Crohn's disease. However, corticosteroids can cause significant adverse events. Budesonide is an alternate enteral glucocorticoid with limited systemic bioavailability.. The primary objective was to evaluate the efficacy and safety of oral budesonide for the induction of remission in Crohn's disease.. The following electronic databases were searched: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane IBD/FBD Group Specialised Trial Register, and ClinicalTrials.gov. Reference lists of articles, as well as conference proceedings were manually searched. Pharmaceutical companies were also contacted.. Randomized controlled trials comparing budesonide to a control treatment were included. The study population included patients of any age with active Crohn's disease (CDAI > 150). The primary outcome was induction of remission (CDAI < 150) by week 8 to 16 of treatment. Secondary outcomes included: time to remission, mean change in CDAI, clinical, histological or endoscopic improvement, improvement in quality of life, adverse events and early withdrawal.. Two independent investigators reviewed studies for eligibility, extracted the data and assessed study quality. A random effects model was used and studies were weighted using the DerSimonian & Laird method. Meta-analysis was performed using RevMan 4.2.10 software.. Twelve studies were included: 9 compared budesonide with conventional corticosteroids, 2 were placebo-controlled, and 1 compared budesonide with mesalamine. After 8 weeks of treatment, budesonide was significantly more effective than placebo (RR 1.96, 95% CI 1.19 to 3.23) or mesalamine (RR 1.63; 95% CI 1.23 to 2.16) for induction of remission. Budesonide was significantly less effective than conventional steroids for induction of remission (RR 0.86, 95% CI 0.76 to 0.98), particularly among patients with severe disease (CDAI > 300) (RR 0.52, 95% CI 0.28 to 0.95). Fewer adverse events occurred in those treated with budesonide compared to conventional steroids (RR 0.64, 95% CI 0.54 to 0.76) and budesonide was better able to preserve adrenal function (RR for abnormal ACTH test 0.65, 95% CI 0.55 to 0.78).. Budesonide is more effective than placebo or mesalamine for induction of remission in Crohn's disease. Although short-term efficacy with budesonide is less than with conventional steroids, particularly in those with severe disease or more extensive colonic involvement, the likelihood of adverse events and adrenal suppression is lower.

Topics: Administration, Oral; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Humans; Randomized Controlled Trials as Topic; Remission Induction

Topics: Adrenal Cortex Hormones; Adult; Age Factors; Anti-Inflammatory Agents; Bone Diseases; Budesonide; Case Management; Child; Controlled Clinical Trials as Topic; Crohn Disease; Delayed-Action Preparations; Disease Susceptibility; Dose-Response Relationship, Drug; Drug Administration Routes; Humans; Hypothalamo-Hypophyseal System; Infections; Meta-Analysis as Topic; Muscular Diseases; Pituitary-Adrenal System; Practice Guidelines as Topic; Remission Induction

Topics: Adrenal Cortex Hormones; Anastomosis, Surgical; Anti-Inflammatory Agents; Antibodies, Monoclonal; Budesonide; Colon; Constriction, Pathologic; Crohn Disease; Dilatation; Endoscopy; Gastrointestinal Agents; Glucocorticoids; Humans; Ileal Diseases; Ileum; Infliximab; Intestinal Obstruction; Magnetic Resonance Imaging; Prosthesis Implantation; Randomized Controlled Trials as Topic; Recurrence; Risk Factors; Time Factors

The therapy of inflammatory bowel diseases is based on 5-aminosalicylates (5-ASAs) that are the forefront of treatment of mild-to-moderate active disease and maintenance; steroids are used for the treatment of moderate-to-severe active disease; immunosuppressives and sometimes antibiotics in moderate-to-severe disease; maintenance and for the treatment of selected complications. The last few years have witnessed a significant change in the treatment of Crohn's disease. Based on evidence from new clinical studies and recent meta-analyses, the role of and indications for conventional therapy have been reassessed. The 5-ASAs are nowadays less frequently used in both active disease and maintenance therapy. Instead, budesonide has been introduced in the treatment of mild-to-moderate ileal disease. Besides the modest use of 5-ASAs, steroids are prescribed for active colonic disease. Immunosuppressives, especially azathioprine, are more commonly used in moderate-to-severe disease as well as in maintenance. The preferred maintenance regimen following medically- and surgically-induced remission, in addition to relationship between medical and surgical therapies, has also changed. The recent introduction of new "biological" therapy represents a major, promising change in the therapy of resistant and penetrating disease.

Topics: Acute Disease; Adrenal Cortex Hormones; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Azathioprine; Budesonide; Chronic Disease; Crohn Disease; Fistula; Gastrointestinal Agents; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Infliximab; Mesalamine; Methotrexate; Severity of Illness Index

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.. 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.. 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.. 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.. 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.

Topics: Algorithms; Budesonide; Crohn Disease; Gastrointestinal Agents; Glucocorticoids; Humans; Predictive Value of Tests; Randomized Controlled Trials as Topic; Remission Induction; Treatment Outcome

Crohn's disease (CD) is a multifactorial disorder of unknown cause. Outstanding progress regarding the pathophysiology of CD has led to the development of innovative therapeutic concepts. Numerous controlled trials have been performed in CD over the last years. However, many drugs have not been approved by regulatory authorities due to lack of efficacy or severe side effects. Therefore, well-known drugs, including 5-ASA, systemic or topical corticosteroids, and immunosuppressants such as azathioprine, are still the mainstay of CD therapy. Importantly, biologicals such as infliximab have shown to be efficacious in problematic settings such as fistulizing or steroid-dependent CD. This review is intended to give practical guidelines to clinicians for the conventional treatment of CD. We concentrated on the results of randomized, placebo-controlled trials and meta-analyses, when available, that provide the highest degree of evidence. We provide evidence-based treatment algorithms whenever possible. However, many clinical situations have not been answered by controlled clinical trials and it is important to fill these gaps through expert opinions. We hope that this review offers a useful tool for clinicians in the challenging treatment of CD.

Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Azathioprine; Budesonide; Crohn Disease; Glucocorticoids; Humans; Immunosuppressive Agents; Infliximab; Mesalamine; Methotrexate; Nutrition Therapy; Randomized Controlled Trials as Topic; Remission Induction

Corticosteroids continue to play a central role in induction of remission in active Crohn's disease. However, their use comes at a price of significant adverse effects when used repeatedly or for extended periods. Newer corticosteroid agents with limited systemic bioavailability offer a tantalizing option, if they can be shown to be efficacious and safer than conventional corticosteroids. Budesonide is the main alternative corticosteroid currently available in an enteric formulation.. To evaluate the effectiveness of oral budesonide for the treatment of acute flares of Crohn's disease. A secondary but important endpoint was to evaluate the adverse effect profile.. The following sources were used to search the literature for potentially relevant papers and trials. 1. A computer-assisted search of the on-line bibliographic database MEDLINE from 1986 onwards. 2. Hand searching the reference lists of trials and review articles identified by means of the computer- assisted search. 3. Proceedings from major gastrointestinal meetings were manually searched from 1990 onwards. 4. Contact with the relevant pharmaceutical companies that have been involved in the development of budesonide.. Potentially relevant articles were reviewed in an independent unblinded fashion by two authors to determine if they met the criteria specified below: 1) STUDY POPULATION: Patients of any age with acutely active Crohn's disease, as defined by a CDAI > 150. 2) METHODOLOGY: Randomized double blind controlled trials comparing budesonide to a control treatment. Patients in the control arm may have received placebo, conventional corticosteroids, 5-aminosalicylic acid or sulfasalazine. 3) OUTCOME MEASURES: Clinical remission was the outcome measure of interest. The definition of remission was usually a CDAI < 150 by 8 to 16 weeks of therapy.. Eligible articles were reviewed in duplicate and the results of the primary research trials were abstracted onto specially designed data extraction forms. The proportion of patients achieving remission in the active treatment and control groups of each study were derived from the data provided in the original research papers. Where possible, data were broken down based on site of disease or other strata used by the individual trials.. Data extracted from the original research articles were converted, where necessary, into individual 2 x 2 tables (remission versus no remission x budesonide versus control) for each of the individual studies. Where available, individual 2 x 2 tables for strata within studies were also used. The presence of significant heterogeneity among studies was tested for using the chi-square test. Because this is a relatively insensitive test for the presence of heterogeneity, a p-value of 0.10 was regarded as statistically significant. Where p < 0.10 the data from the individual studies were still combined but the pooled results were interpreted with caution. The 2 x 2 tables were synthesized into a summary test statistic using the pooled odds ratio and 95% confidence intervals as described by Cochran and Mantel and Haenszel. A fixed effects model was used for the pooling of data. The analysis was performed initially by combining data from all trials to estimate the response rate to budesonide therapy. The analysis was also performed by combining only studies with comparable control groups.. Eight studies were deemed eligible for review.. Budesonide was superior to placebo for induction of remission with a pooled odds ratio for the two placebo-controlled trials of 2.85 (95% CI 1.67 - 4.87). A single trial comparing budesonide with mesalamine demonstrated an odds ratio of 2.80 (95% CI 1.50 - 5.20) in favour of budesonide over mesalamine for induction of remission in active Crohn's disease. However, budesonide was inferior to conventional corticosteroids (prednisone or prednisolone) for induction of remission with a pooled odds ratio for the five trials of 0.69 (95% CI 0.51 - 0.95).. The two trials comparing budesonide versus placebo (Greenberg 1994; Tremaine 2002) showed no difference between study groups for proportion of reported corticosteroid-related adverse effects with the pooled odds ratio for both trials of 0.98 (95% CI 0.58 - 1.67). Five trials comparing budesonide versus prednisone showed the budesonide study group had fewer reported corticosteroid-related adverse effects than the prednisone study group (pooled odds ratio was 0.38 (95% CI 0.28 - 0.53).. With disease in the ileum or ascending colon, budesonide offers an effective therapy which is somewhat less efficacious but with fewer adverse effects than conventional corticosteroids (e.g. prednisone, prednisolone, or 6-methylprednisolone).

Topics: Administration, Oral; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Humans; Randomized Controlled Trials as Topic; Remission Induction

In Crohn's disease therapeutic concepts are according to distinct conditions. Course of the disease, the individual disease pattern and the aim of treatment are of particular significance. Care of patients with Crohn's disease requires interdisciplinary cooperation between gastroenterologists and surgeons. Primary therapy in mild to moderate disease comprises aminosalicylates and budesonide. Treatment of refractory or severe cases are corticosteroids. Immunosuppressive therapy is indicated in all kinds of complicated disease. First line immunosuppressants are Azathioprine and 6-Mercaptopurine while Methotrexate, Infliximab, Mycophenolatmofetil and other compounds represent alternative or rescue medications. Maintenance of remission should not be done on a regular basis but rather regarding the individual patients' situation. Risks have to be carefully balanced with possible benefits. The most important aim of treatment is quality of life.

Topics: Acute Disease; Adrenal Cortex Hormones; Adult; Algorithms; Aminosalicylic Acids; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Azathioprine; Budesonide; Child; Crohn Disease; Drug Therapy, Combination; Gastrointestinal Agents; Humans; Immunosuppressive Agents; Infliximab; Mercaptopurine; Methotrexate; Mycophenolic Acid; Practice Guidelines as Topic; Prognosis; Remission Induction; Risk Factors; Time Factors

More than half of Crohn's disease patients require surgery during the course of their disease. Although endoscopic recurrence does not necessarily imply that patients have symptom recurrence, the high need for repeated surgery indicates that lesions gradually developing after surgical remission lead to fibrostenosis or other complications. Despite multiple clinical trials a clear medical strategy to prevent disease recurrence has not been identified. Future well designed collaborative trials with specified end points are needed to optimize clinical practice in the prevention of postoperative Crohn's disease recurrence.

Topics: Aminosalicylic Acids; Anti-Bacterial Agents; Budesonide; Crohn Disease; Decision Trees; Humans; Mercaptopurine; Postoperative Period; Recurrence

This overview summarises available pharmacokinetic data on budesonide capsules (Entocort EC), approved for the treatment of mild-to-moderate active Crohn's disease involving the ileum and/or ascending colon and for prolongation of symptom control. Budesonide is a locally-acting glucocorticosteroid with an extensive, primarily hepatic, metabolism after oral administration. It is rapidly absorbed and biotransformed by cytochrome P450 (CYP) 3A to metabolites with negligible glucocorticoid activity. Entocort EC, a pH- and time-dependent oral formulation of budesonide, was developed to optimise drug delivery to the ileum and throughout the colon. Pharmaco-scintigraphic studies have confirmed that the Entocort EC formulation delays budesonide absorption and prolongs the rate of elimination but maintains complete absorption. This improves the delivery of budesonide to the intestinal lumen relative to a plain formulation. A low systemic availability of 9-21% indicates extensive first-pass elimination. Food appears to have little impact on the absorption of budesonide from Entocort EC capsules and the pharmacokinetics are dose-proportional between 3 and 15 mg. On average, systemic availability was 2.5-fold higher in patients with cirrhosis compared with healthy controls; however, mild liver impairment had little effect on systemic exposure. Pharmacokinetics appear unaffected by gender and age, although this has not been tested in younger children. Renal impairment is not expected to have an impact on the kinetics of Entocort EC. Budesonide is unlikely to inhibit the metabolism of other drugs, including CYP3A4 substrates, mainly because of the very low plasma concentrations obtained with the compound even after high doses of Entocort trade mark EC capsules. Strong CYP3A4 inhibitors, such as ketoconazole, will inhibit the metabolism of budesonide, resulting in several-fold increases in the area under the concentration-time curve of budesonide. Also, grapefruit juice intake may increase systemic availability of budesonide, probably by inhibition of intestinal CYP3A4 activity. Unlike prednisolone, oral contraceptives do not alter plasma budesonide concentrations. An increased pH obtained by gastric acid inhibitory drugs, such as omeprazole, does not affect the pharmacokinetics of budesonide. In summary, budesonide capsules (Entocort EC) possess many pharmacological features that make the formulation well adapted for a targeted treatment of inflammatory disorders, such

Topics: Adult; Aged; Animals; Anti-Inflammatory Agents; Area Under Curve; Biological Availability; Budesonide; Capsules; Crohn Disease; Female; Food-Drug Interactions; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Rats

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.

Topics: Algorithms; Aminosalicylic Acids; Anti-Bacterial Agents; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Colorectal Neoplasms; Crohn Disease; Drug Administration Schedule; Humans; Patient Compliance; Patient Education as Topic; Quality of Life; Risk Factors; Severity of Illness Index; Time Factors; Treatment Outcome

Topics: Adrenal Cortex Hormones; Adult; Aminosalicylic Acids; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Azathioprine; Budesonide; Colitis, Ulcerative; Colonoscopy; Controlled Clinical Trials as Topic; Crohn Disease; Diagnosis, Differential; Female; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Magnetic Resonance Imaging; Mercaptopurine; Methotrexate; Metronidazole; Pouchitis; Remission Induction; Tacrolimus; Time Factors; Tomography, X-Ray Computed; Ultrasonography

Crohn's disease and ulcerative colitis are the most frequent inflammatory bowel diseases (IBD) with a prevalence of approximately one out of 500. Cytokine research opened new and potent treatment options and thus stimulated clinical and basic research.However, the IBD still remain a challenge for patients and physicians,demanding close cooperation between gastroenterologists,radiologists and surgeons. The basic understanding of IBD,which is necessary for efficient diagnostic and therapeutic concepts is reviewed.. Based upon recent publications and our clinical experience we discuss aspects of etiology,pathogenesis,diagnostics,and therapy of Crohn's disease and ulcerative colitis.. A genetically influenced, exaggerated and sustained immune response against the own gut flora seems to be one of the most important factors in the pathogenesis of IBD. Not less important are environmental influences. For instance, cigarette smoking had been judged to have some negative influence on the natural course of Crohn's disease.Now,however, recent studies show that smoking is even a significant independent risk factor in the pathogenesis of IBD. Since IBD and especially Crohn's disease can effect the whole body, detailed analysis of inflammatory organ involvement is necessary before therapy. For instance, the MRI enteroclysis technique adds a necessary diagnostic tool for the exploration of those parts of the small bowel that cannot been reached by routine endoscopy like the upper ileum and the lower jejunum. In terms of therapy, a change of paradigms can be observed: patients will no longer be treated only when symptoms arise, but will early be integrated into a therapeutic concept, which is determined by site and extent of the disease and adapted to the abilities and needs of the patient.Furthermore,immunosuppressive agents like azathioprine and 6-mercaptopurine will establish as central concept in the medical treatment of IBD.. IBD-therapy should rather be adapted to the patient's individual inflammatory pattern than be oriented to schematic treatment rules. New endoscopic and radiologic techniques provide the necessary diagnostic tools.

Topics: Adrenal Cortex Hormones; Adult; Anti-Inflammatory Agents; Antibodies, Monoclonal; Azathioprine; Budesonide; Colitis, Ulcerative; Colonoscopy; Crohn Disease; Cyclosporins; Diagnosis, Differential; Gastrointestinal Agents; Humans; Ileostomy; Immunosuppressive Agents; Inflammatory Bowel Diseases; Infliximab; Meta-Analysis as Topic; Methotrexate; Parenteral Nutrition; Prednisolone; Quality of Life; Time Factors; Ultrasonography

In this chapter, the state-of-the-art treatment of Crohn's disease is summarized; the chapter intends to provide an uptodate knowledge of current treatment strategies of Crohn's disease. The indications for steroids and for immunomodulators are described and compared to newer approaches based on neutralizing tumor necrosis factor by specific antibodies (Infliximab). An attempt was made to clearly differentiate between evidence-based treatment schemes and those which are not supported by good evidence. The chapter was written for daily practice; the proposed treatment algorithms should support the physician in his daily work.

Topics: Acute Disease; Adjuvants, Immunologic; Adrenal Cortex Hormones; Algorithms; Aminosalicylic Acids; Anti-Bacterial Agents; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Azathioprine; Budesonide; Case-Control Studies; Clinical Trials as Topic; Crohn Disease; Drug Therapy, Combination; Gastrointestinal Agents; Humans; Immunosuppressive Agents; Infliximab; Mesalamine; Methotrexate; Metronidazole; Osteoporosis; Prednisolone; Prednisone; Randomized Controlled Trials as Topic; Time Factors

After first resection in Crohn's disease at 1 year 60-80% of patients have endoscopic recurrence, 10-20% have clinical relapse, and 5% have surgical recurrence.1, 2 This review focuses on the actual evidence on the prevention of recurrence and relapse dealing with risk factors and with drugs. Smoking is the only risk factor for Crohn's disease, that has been shown to be related to both endoscopic and surgical recurrence and relapse. Among the different drugs evaluated, some (Mesalamine and Metronidazole) have been shown to be effective, whereas others (immunosuppressive) need to be evaluated in further, new trials.

Topics: Anti-Infective Agents; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Crohn Disease; Humans; Immunosuppressive Agents; Mesalamine; Metronidazole; Ornidazole; Probiotics; Risk Factors; Secondary Prevention; Smoking

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.

Topics: Administration, Topical; Algorithms; Anti-Bacterial Agents; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Controlled Clinical Trials as Topic; Crohn Disease; Gastrointestinal Agents; Glucocorticoids; Humans; Mesalamine; Sulfasalazine

To review the pharmacology, pharmacokinetics, efficacy, and safety of oral budesonide (Entocort EC) in the treatment of mild to moderate Crohn's disease (CD).. The MEDLINE database (1966-December 2002) was searched using the key words budesonide and inflammatory bowel diseases and restricted to the English language. The references from relevant articles were also reviewed for additional citations.. Articles and abstracts that evaluated oral budesonide for management of CD were considered, with emphasis on randomized, controlled clinical trials.. Budesonide's high potency at the glucocorticoid receptor and extensive first-pass hepatic metabolism result in a topical antiinflammatory effect on intestinal tissue, with minimal systemic glucocorticoid adverse effects. Clinical trials have demonstrated that budesonide is effective in the treatment of patients with mild to moderate CD of the ileum and ascending colon, with efficacy similar to prednisolone and superior to mesalamine. Long-term therapy with budesonide increased the duration of CD remission, but the effect was not sustained up to 1 year. Budesonide failed to prevent postsurgical relapse of CD. Adrenal suppression and glucocorticoid-related adverse effects have been reported at lower rates in patients treated with budesonide compared with prednisolone. Patients prescribed budesonide should be monitored for hepatic dysfunction and potential drug interactions.. Budesonide is an effective and relatively safe option for treatment of mild to moderate CD of the ileum and ascending colon.

Topics: Administration, Oral; Budesonide; Crohn Disease; Humans; Meta-Analysis as Topic

Conventional corticosteroid therapy effectively induces remission of Crohn's disease (CD) across a range of disease severity. However, alternative treatments are needed for patients with disease unresponsive to corticosteroids, patients requiring maintenance therapy (for which corticosteroids are ineffective), corticosteroid-dependent patients, and patients with corticosteroid-related toxicities. Thus, corticosteroid-sparing effects are an important clinical endpoint for treatments of CD. Budesonide offers comparable efficacy with less short-term toxicity than conventional corticosteroids (prednisone, prednisolone); this agent has also demonstrated short-term remission maintenance efficacy, while potentially enabling withdrawal of more toxic corticosteroids in corticosteroid-dependent patients. However, budesonide has not shown long-term maintenance benefit in clinical studies, and the risk for and implications of budesonide dependency need further evaluation. The immunomodulators, azathioprine and 6-mercaptopurine, are most effective for maintenance of remission in quiescent disease, but may be useful in conjunction with other therapies in inducing remission in active CD; methotrexate may be considered an alternative because of its efficacy in inducing and maintaining remission. In clinical trials, treatment with azathioprine/6-methotrexate has enabled corticosteroid withdrawal in 55% of patients, and methotrexate, in 39% of patients with corticosteroid-dependent CD, while maintaining clinical response. Monitoring for infrequent hematological or hepatic toxicity is recommended during use of these immunomodulators. Infliximab is effective for induction and maintenance of remission in patients with refractory CD participating in randomized placebo-controlled studies and, in open-label experience, has enabled corticosteroid withdrawal in approximately three quarters of patients. This biological agent is generally well tolerated. Infusion reactions are the most commonly occurring side effects; such reactions may require adjustment of infusion rate and/or treatment with an antihistamine or acetaminophen. The investigational biological agent CDP-571 has also shown corticosteroid-sparing efficacy in patients with CD. In conclusion, recent research has helped identify corticosteroid-sparing treatments that can provide benefit in patients with corticosteroid-dependent and/or corticosteroid-refractory CD or patients at risk for corticosteroid-induced toxicities.

Topics: Adjuvants, Immunologic; Adrenal Cortex Hormones; Algorithms; Anti-Inflammatory Agents; Budesonide; Clinical Trials as Topic; Crohn Disease; Humans

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.. 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.. 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.. 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.. 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.

Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Crohn Disease; Glucocorticoids; Humans; Mesalamine; Randomized Controlled Trials as Topic; Remission Induction

Topics: Anti-Inflammatory Agents; Budesonide; Crohn Disease; Humans

Budesonide (Entocort EC Capsules) is an oral corticosteroid with a high degree of topical activity and low systemic bioavailability (approximately 11%). This action is achieved by a high affinity for the glucocorticoid receptor and an extensive first-pass hepatic metabolism. The budesonide capsule has been formulated to dissolve in a pH dependent manner, delivering most of the drug to the ileum and ascending colon, areas of the intestine most commonly affected by Crohn's disease. In large (n > or = 176), well designed clinical trials of 10 to 12 weeks' duration in patients with active, mild to moderate Crohn's disease, budesonide (9 mg/day) was significantly more effective in inducing remission than placebo or mesalazine (mesalamine) slow release, and demonstrated similar efficacy to recommended dosages of prednisolone. Results of health-related quality-of-life assessments support clinical data, showing a significantly greater improvement among patients treated with budesonide than with placebo or mesalazine slow release. Oral budesonide was well tolerated in clinical trials of up to 16 weeks' duration. In these studies, the incidence of adverse events associated with budesonide (9 mg/day) was similar to that seen with placebo and mesalazine slow release. The rate of glucocorticoid-related adverse effects observed with budesonide was significantly less than that reported with prednisolone.. Oral budesonide 9 mg/day offers efficacy that is superior to mesalazine slow release and placebo, and similar to prednisolone in the treatment of patients with active mild to moderate Crohn's disease involving the ileum and/or ascending colon. Budesonide is generally well tolerated and the incidence of adverse events is similar to that seen with placebo or mesalazine slow release. Glucocorticoid-related adverse effects are significantly less frequent during short-term therapy with budesonide than with prednisolone. Thus, for the medical management of patients with active mild to moderate Crohn's disease, oral budesonide has superior efficacy to mesalazine slow release and a more favourable tolerability profile than prednisolone.

Topics: Administration, Oral; Adult; Anti-Inflammatory Agents; Biological Availability; Budesonide; Crohn Disease; Databases, Factual; Humans; Hydrocortisone; MEDLINE; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome

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.

Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Crohn Disease; Humans; Mesalamine; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome

Linear growth retardation is a major complication of Crohn's disease that occurs in children. It is related both to undernutrition and to direct effects of the inflammatory process on the growth axis. Enteral nutrition (elemental, semi-elemental or polymeric diet) employed as the sole source of nutrition remains a mainstay of treatment of active Crohn's disease because it corrects nutritional deficits, has anti-inflammatory effects, heals mucosal inflammation and stimulates growth. Conventional corticosteroids have adverse effects on growth and preliminary data suggest that an ileal-release preparation of budesonide may also suppress linear growth. 6-Mercaptopurine (6-MP) and its prodrug azathioprine maintain remission in children with Crohn's disease. These treatments thus have the potential to improve growth velocity and final adult height.

Topics: Adrenal Cortex Hormones; Budesonide; Child; Child Nutritional Physiological Phenomena; Crohn Disease; Diet; Growth Disorders; Humans; Mercaptopurine

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Cytokines; Humans; Immunosuppressive Agents

Although new salicylates are now available for the treatment of ulcerative colitis, sulphasazaline still has an important therapeutic role. The role of salicylates in Crohn's disease is limited to the mild activity phase; further data are required to clarify its role in maintenance on remission. New steroids are a real alternative to traditional steroids in active ulcerative colitis and Crohn's disease.

Topics: Acute Disease; Aspirin; Beclomethasone; Budesonide; Colitis, Ulcerative; Crohn Disease; Drug Therapy, Combination; Glucocorticoids; Humans; Inflammatory Bowel Diseases; Prednisolone; Randomized Controlled Trials as Topic; Salicylates; Sulfasalazine

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Biomarkers; Biopsy; Budesonide; Carrier Proteins; Crohn Disease; Cytokines; Humans; Infliximab; Intracellular Signaling Peptides and Proteins; Mutation; Nod2 Signaling Adaptor Protein; Nutritional Support; Prednisolone; Reference Standards

Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Azathioprine; Budesonide; Crohn Disease; Gastrointestinal Agents; Humans; Immunosuppressive Agents; Infliximab; Mesalamine; Methotrexate; Secondary Prevention; Treatment Outcome

Budesonide modified-release capsule is an effective form of therapy for the treatment of Crohn's disease located in the distal ileum, ileocecal region, and ascending colon. Because some of the benefit of budesonide therapy results from local effects, this agent will not be very effective in the treatment of patients with extensive colitis or left-side colitis. Budesonide is equal to less effective than prednisolone or prednisone therapy in the treatment of active Crohn's disease, but is associated with fewer glucocorticoids adverse reactions.

Topics: Administration, Oral; Administration, Topical; Anti-Inflammatory Agents; Budesonide; Capsules; Crohn Disease; Glucocorticoids; Humans

The primary objective was to precisely derive an estimate of the efficacy of oral budesonide for the maintenance of remission in Crohn's disease.. Medline 1966-September 2000 was searched using the text and key words "oral budesonide", "Crohn's disease", "Crohn disease", and "inflammatory bowel disease". Proceedings from the American Gastroenterology Association conference (1980-1998) were hand searched. Additionally, the Cochrane Controlled Trials Register and the Inflammatory Bowel Disease Review Group Trials Registers were also searched. The manufacturer of oral budesonide was also contacted, as were some of the local trialists involved in the oral budesonide trials. Relevant articles were retrieved, and their reference lists were also reviewed.. Randomized controlled trials of oral budesonide in which patients at entry were in remission with a Crohn's Disease Activity Index (CDAI) <= 150, and had disease restricted to the ileum and colon.. The primary outcome was the relative risk (RR) of relapse (and 95% confidence interval [CI]) during the 12 months of treatment, as defined by the number of patients who relapsed, and the number of patients who entered the trial. The numbers needed to treat were also derived.. Three randomized controlled trials of oral budesonide (controlled ileal release preparation) 6 mg/day, 3mg/day and placebo for a one year period were included in the analysis. Budesonide 6 mg/day was not effective at preventing relapse of Crohn's disease over the 12 months of treatment. The relative risk of relapse was 0.89 (95% CI: 0.71-1.13) comparing budesonide 6 mg/day and placebo. Similar results were also observed in the comparison of budesonide 6 mg/day with budesonide 3 mg/day; the relative risk of relapse was 0.89 (95% CI: 0.70-1.11). The 3 mg/day dose was similarly found to be ineffective at preventing relapse during the 12 months of treatment; the relative risk of relapse was 1.00 (95% CI: 0.80-1.24). The results of the analysis of relative risk of relapse were supported by the analysis of withdrawal due to treatment failure. The relative risks for withdrawal due to treatment failure for budesonide 6 mg/day compared with placebo was 0.85 (95% CI: 0.65-1.10), for budesonide 3 mg/day compared with placebo was 0.94 (95% CI: 0.73-1.20), and for budesonide 6 mg/day compared with budesonide 3 mg/day was 0.89 (95% CI: 0.68-1.17).. Oral budesonide therapy at 6 mg/day is not effective in preventing relapses of Crohn's disease.

Topics: Administration, Oral; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Humans; Randomized Controlled Trials as Topic; Recurrence; Remission Induction; Risk

Despite conventional medical and/or surgical intervention, endoscopic and symptomatic relapse is common among individuals with Crohn's disease (CD). Treatment goals have therefore been refocused to include achieving control of active disease and maintaining remission with agents associated with a minimum of toxic adverse effects. Conventional treatment regimens have been used with varying success in regard to these therapeutic goals. Traditionally, aminosalicylates have been considered effective in inducing a response in some patients with mild-to-moderate CD but have demonstrated little or no long-term benefit in controlled clinical trials. Glucocorticosteroid therapy is associated with higher rates of response in patients with active CD; however, clinical benefits are frequently offset by the common occurrence of corticosteroid-related toxicity. Oral controlled-release budesonide has demonstrated comparable efficacy to prednisolone with less risk for adverse effects, although many questions remain regarding the long-term use of this agent. Response to standard immunosuppressive agents such as azathioprine and 6-mercaptopurine in patients with active disease may require 3 to 6 months from initiation of treatment. These agents are therefore considered most valuable as maintenance therapy, providing consistent long-term benefit in patients with chronic refractory or corticosteroid-dependent disease. Although the incidence of allergic adverse effects is relatively low with azathioprine/6-mercaptopurine, more serious adverse effects, including bone marrow suppression, hepatotoxicity, pancreatitis, and infectious complications, can occur. Limited success in the treatment of perianal disease has been achieved with antibiotics such as metronidazole and the immunosuppressives cyclosporine and azathioprine/6-mercaptopurine. Although broader use of immunosuppressive agents has allowed improvement in the maintenance of remission in patients with CD, long-term safety data with these agents are lacking, concerns about toxicity and the potential risk for neoplasia remain, and attenuation of response with chronic immunosuppressive use can occur. Therefore, innovative therapeutic approaches are needed to meet key treatment goals often not addressed by conventional therapies.

Topics: Aminosalicylic Acids; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Azathioprine; Budesonide; Clinical Trials as Topic; Crohn Disease; Humans; Immunosuppressive Agents; Mercaptopurine; Mesalamine; Methotrexate; Prednisone; Quality of Life; Recurrence; Sulfasalazine; Treatment Outcome

Corticosteroids are considered a drug of choice for the treatment of patients with moderately to severely active Crohn's disease (CD), an inflammatory bowel disease characterized by chronic recurrent flares of disease activity. However, among patients receiving corticosteroid therapy for induction of remission, 20% have corticosteroid-refractory disease and 36% of those with an initial response develop corticosteroid dependency within 1 year. Chronic corticosteroid exposure in patients who are corticosteroid dependent increases the risk for serious drug-related adverse effects. Withdrawal or reduction of corticosteroid therapy without exacerbation of symptoms is therefore recognized as an important goal of treatment. Therapies that have been shown to facilitate "steroid sparing' include the immunomodulators azathioprine/6-mercaptopurine and methotrexate and the antitumor necrosis factor-alpha monoclonal antibody infliximab. In corticosteroid-dependent patients, budesonide may be substituted for conventional corticosteroid therapy without loss of response and with less risk for toxicity, but its long-term efficacy requires further evaluation. A preliminary controlled study suggests that the investigational anti-TNF monoclonal antibody CDP-571 may also be clinically beneficial as a corticosteroid-sparing agent. This review summarizes the clinical evidence that supports consideration of these agents as alternatives in patients with CD who are dependent on, refractory to, or intolerant of conventional corticosteroid therapy.

Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Azathioprine; Budesonide; Clinical Trials as Topic; Crohn Disease; Cyclosporine; Etanercept; Female; Gastrointestinal Agents; Humans; Immunoglobulin G; Immunosuppressive Agents; Infliximab; Male; Mercaptopurine; Methotrexate; Receptors, Tumor Necrosis Factor; Thalidomide; Treatment Outcome

Placebo controlled trials have demonstrated that a tapering course of corticosteroids is an effective therapy for active Crohn's disease. A population-based study of 109 patients with Crohn's disease undergoing their first course of corticosteroids showed that, at the end of one year, 44% of patients were steroid responsive, 36% were steroid dependent and 20% were steroid refractory. Side effects occur frequently during a four-month tapering course of corticosteroids, including moon face, acne, infection, ecchymoses, hypertension, hirsutism, petechial bleeding and striae. More serious side effects occur with long term use, including hypertension, diabetes, infection, osteonecrosis, osteoporosis, myopathy, cataracts, glaucoma and psychosis. Low dose corticosteroids, alternate-day corticosteroids and mesalamine (5-aminosalicylate) are not effective steroid-sparing agents in patients with Crohn's disease. Controlled ileal release budesonide, 6 mg/day, is an effective steroid-sparing agent, but it does result in some decrease in adrenal function. Azathioprine, 6-mercaptopurine and methotrexate are all effective steroid-sparing agents, as is the humanized, anti-tumour necrosis factor monoclonal antibody, CDP571. A preliminary, uncontrolled study has suggested that the mouse/human chimeric monoclonal antibody infliximab may also be steroid sparing. Surgical resection is an effective strategy to reduce steroid use in the short to intermediate term, but postoperative reoccurrence of Crohn's disease occurs frequently. Given the morbidity associated with prolonged corticosteroid use, medical and surgical treatment strategies to reduce steroid use should be employed routinely.

Topics: Anti-Inflammatory Agents; Budesonide; Crohn Disease; Glucocorticoids; Humans; Immunosuppressive Agents; Treatment Outcome

To perform a meta-analysis to assess the effectiveness and safety of oral budesonide for inducing remission in active Crohn's disease and for preventing relapse in Crohn's disease with medically- or surgically-induced remission.. All randomized, double-blind controlled trials involving oral budesonide therapy in Crohn's disease were retrieved from a Medline search, reviews articles or their bibliographies. Of 83 articles retrieved, 12 met the inclusion criteria. Data extraction was performed by three independent observers and scoring disagreements were resolved by consensus.. Six trials tested budesonide in active disease and six in quiescent disease. Budesonide was less effective than conventional corticosteroids for inducing remission of active Crohn's disease (pooled rate difference, RD -8.5%; 95% CI: -16.4 to -0.7%; P=0.02), but corticosteroid-related adverse events were reduced (RD -22.4%; 95% CI: -32 to -12.8%; P < 0.001). In quiescent Crohn's disease, budesonide was as effective as placebo for preventing relapse in medically induced remission (RD -0.8%; 95% CI: -9.9 to 8.3%; P=0.42) and endoscopic recurrence in surgically induced remission (RD -3.5%; 95% CI: -16.9 to 9.8%; P=0.30). In the long term treatment, budesonide had an occurrence rate of corticosteroid-related adverse effects similar to placebo (RD 5.3%; 95% CI: -3.9 to 14.5%; P=0.30).. Budesonide is significantly less effective than conventional corticosteroids for inducing remission in active Crohn's disease, but the risk of corticosteroid-related adverse effects is significantly reduced. Budesonide is not effective in preventing relapse of Crohn's disease after medically- or surgically-induced remission.

Topics: Administration, Oral; Administration, Topical; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Double-Blind Method; Glucocorticoids; Humans; Randomized Controlled Trials as Topic

Until a cure for Crohn's disease(s) is found, strategies that prolong the time spent in remission offer the greatest hope for reducing the morbidity and significant social costs associated with the disease. Medical therapy to date has been disappointing, and the search for a safe, effective therapy that could be offered at low cost continues. The aminosalicylates, so effective in ulcerative colitis, have shown, at best, minimal efficacy in maintaining remission in Crohn's disease. Conventional corticosteroids are not effective, and any reduction in time to relapse for budesonide-treated patients is measured in weeks not months. Azathioprine, 6-mercaptopurine, and methotrexate are effective in maintaining remission, but all three have significant side effects. Antibiotics may have a role to play. Biological therapy may be considered, but the issues of cost and long-term safety require evaluation. Future studies should segregate patients into two groups, those with a medically induced remission and patients whose concern is the prevention of postoperative recurrence.

Topics: Budesonide; Crohn Disease; Gastrointestinal Agents; Humans; Mesalamine; Secondary Prevention

Budesonide in the pH-dependent and time-dependent release preparation is at a dose of 9 mg/day useful for treatment of mild to moderate active Crohn's disease. Although the remission rates are somewhat lower as compared to systemic steroids, the number of side effects is significantly decreased. Differences between both preparations based on theoretical and pharmacological considerations have not yet been proven in clinical practice. With regard to maintenance of steroid-induced remission the data available do not justify continuous treatment. This is also true for postoperative remission maintenance. It is not clear at the moment if higher doses could possibly be effective for this indication. It has to be expected, however, that side effects than will increase as well.

Topics: Anti-Inflammatory Agents; Budesonide; Clinical Trials as Topic; Crohn Disease; Delayed-Action Preparations; Drug Delivery Systems; Humans; Treatment Outcome

Budesonide in both galenic forms is suitable for the treatment of a flare of Crohn's disease of up to moderate activity. The same holds true for 5-amino-salicylates, although they are less effective. Topical steroids delay but do not prevent relapses. Aminosalicylates may be used in the postoperative situation for prevention of relapse but are not significantly effective after drug-induced remission.

Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Clinical Trials as Topic; Crohn Disease; Drug Delivery Systems; Humans; Mesalamine; Treatment Outcome

Topics: Anti-Inflammatory Agents; Budesonide; Clinical Trials as Topic; Colitis, Ulcerative; Crohn Disease; Humans; Hydrocortisone; Inflammatory Bowel Diseases; Meta-Analysis as Topic; Multicenter Studies as Topic; Prednisolone

Topics: Anti-Inflammatory Agents; Budesonide; Crohn Disease; Humans; Mesalamine; Prednisolone

Crohn's recurrence is the appearance of objective signs defined radiologically, endoscopically or pathologically of Crohn's disease in the bowel of a patient who has previously had a resection of all macroscopically diseased tissue. New lesions can be visualized endoscopically within weeks to months after ileal resection and ileocolonic anastomosis in the neoterminal ileum. The evolution of these lesions mimics the natural history of ileal Crohn's disease at the onset. If we are able to prevent recurrence of early lesions we would probably interrupt the natural course of the disease. The drugs tested until today include different 5-ASA formulations, metronidazole and budesonide. 5-ASA seems to have a limited protective effect. High dose metronidazole started immediately after surgery decreases endoscopic and symptomatic recurrence rates but is associated with a lot of side effects. Budesonide 6 mg/day o.m. reduces endoscopic recurrence after one year only in patients operated upon for inflammatory activity. Studies with immunosuppression for recurrence prevention are currently underway. Thus, today 5-ASA-formulations are recommended as general pharmaco-prophylaxis.

Topics: Anti-Inflammatory Agents; Budesonide; Colon; Crohn Disease; Follow-Up Studies; Humans; Ileum; Mesalamine; Metronidazole; Postoperative Complications; Recurrence

The medical management of Crohn's disease has changed in recent years, but the mainstay of treatment is still prednisone. A substantial fraction of steroid-treated patients are refractory to therapy and addition of azathioprine or methotrexate has a corticosteroid-sparing effect and increases duration of remission. Controlled ileal release budesonide (9 mg daily) induces clinical remission in 60-70% of patients with Crohn's ileitis or right-sided colitis, and continued budesonide treatment has a finite effect on the duration of remission. The efficacy of mesalazine in active Crohn's disease is limited and high doses are required (4000 mg/day). The role of mesalazine in Crohn's disease in remission is disputed, and there is no evidence of a corticosteroid-sparing effect.

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Azathioprine; Budesonide; Clinical Protocols; Crohn Disease; Cyclosporine; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Mesalamine; Methotrexate; Prednisone; Remission Induction; Treatment Outcome

Crohn's disease is inevitably characterized by episodes of relapse followed by remission. The majority of patients will require at least one resection, unfortunately many will have, at some time in the future, further recurrences requiring additional surgery. Faced with this clinical situation, the physician or surgeon may respond to the therapeutic imperative, i.e., it is better to do something rather than to do nothing at all (i.e., treat the patient). Because of these factors, various authors have suggested that the aminosalicylates or, in certain cases, azathioprine, should be prescribed following resection. From a health system point of view, the case for maintenance therapy must be reviewed against several criteria. First, the therapy to be prescribed must be safe for patients over the long term. For the most part, the safety profile of mesalamine has been well established. There is also increasing evidence for the safety of azathioprine when used in chronic inflammatory diseases such as rheumatoid arthritis. Second, there must be objective evidence of efficacy as assessed by randomized controlled, double-blind trials. To date, several trials have been performed, unfortunately, the most recent have only been reported in abstract form. The results of the trials have been contradictory with a mixture of positive and negative findings. There is a lack of consistency for both the dose response and preferred disease site, the use of placebos, the evaluation of outcome and the statistical analysis. Third, the cost-benefit ratio must favour the therapy. Calculation of the number to reat (NNT) to prevent one recurrence is often helpful. Finally, compliance in a group of patients who often decide on surgery so that they can stop taking medication must be considered. A variety of criteria have been developed to assist in making choices regarding prophylaxis. The first relates to the ease of treating the patient with recurrence. Some patients will respond promptly to conventional therapy and enter remission. Unfortunately, this is not the case for the majority of patients. We lack predictors of response. The second concerns the issue as to whether or not the condition to be prevented, recurrence, is a "serious" event. There would be little discussion of that issue at an IBD meeting! The third considers the possibility of adverse events related to the prophylaxis. Again, there does not appear to be concern related to safety. It is the final criterion regarding

Topics: Anti-Inflammatory Agents, Non-Steroidal; Azathioprine; Budesonide; Crohn Disease; Digestive System Surgical Procedures; Humans; Mesalamine; Metronidazole; Postoperative Period; Prognosis; Randomized Controlled Trials as Topic; Secondary Prevention

Glucocorticosteroids are the mainstay of treatment of active Crohn's disease and ulcerative colitis. These drugs however carry important cosmetic short-term side effects and when used long-term they induce severe irreversible complications. Topically acting glucocorticosteroids, especially budesonide, have been designed to achieve local effect at the site of inflammation without systemic effects of the drug. The first results of clinical trials are promising and budesonide has been shown to have an improved safety with almost comparable efficacy in comparison with prednisolone. The optimal enema dose seems to be 2 mg/100 ml at night whereas 9 mg o.m. is the optimal dose to treat ileal or right ileocolonic Crohn's disease. Topically acting GCS, like standard GCS are not effective for maintenance of remission of Crohn's disease or recurrence prevention after resection of the involved Crohn's segment.

Topics: Administration, Oral; Administration, Topical; Anti-Inflammatory Agents; Budesonide; Clinical Trials as Topic; Crohn Disease; Glucocorticoids; Humans

Inflammatory bowel diseases remain a significant chronic disease affecting children and adolescents. Although corticosteroids remain the standard form of therapy for many patients, an era of biological agents for therapy in inflammatory bowel diseases is upcoming with human trials using these agents now forthcoming. In addition, studies on maintenance of remission are beginning to address the selection of those patients most likely to benefit from aminosalicylate therapies, the risks of relapse from using cyclooxygenase inhibitors, the lack of benefit from lipoxygenase inhibitors, and possible future methodologies to examine the effectiveness of the immuno-suppressive agent 6-mercaptopurine. Further development of the hypothesis that new-onset disease may be different than longstanding disease can be appreciated with reports of cytokine analysis in new-onset inflammation and the high risk of progression of disease in new-onset ulcerative proctitis in children. With more reports on the role of intestinal epithelial cells in intestinal diseases, it is now clear that this cell layer is not a passive bystander with regard to the interactions between the luminal contents and immune system components found within the lamina propria; new studies suggest that novel therapeutic strategies may be possible. This review summarizes recently reported aspects of Crohn's disease and ulcerative colitis, with an emphasis on issues-pertinent for younger patients.

Topics: Anti-Inflammatory Agents; Budesonide; Chemokine CXCL5; Chemokines, CXC; Chemotaxis, Leukocyte; Child; Colitis, Ulcerative; Crohn Disease; Humans; Interleukin-10; Interleukin-8; Nutritional Status

Modern medical therapy is increasingly based on evidence. The evidence presented here is that budesonide (Entocort, Astra Pharma) 9 mg/day is superior to placebo and equivalent to systemically active glucocorticosteroids in achieving disease remission in patients with active Crohn's disease, and in prolonging the recurrence time of symptomatic disease. Budesonide causes less disturbance to adrenal function than prednisone or prednisolone and may cause fewer steroid-associated symptoms. Thus, budesonide is the safer, more effective steroid of choice to treat patients with Crohn's disease.

Topics: Anti-Inflammatory Agents; Budesonide; Crohn Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Prednisolone; Pregnenediones; Prognosis; Randomized Controlled Trials as Topic; Remission Induction

Budesonide is a glucocorticoid with high local activity but much lower systemic availability than prednisolone. Topical formulations have long been licensed for use in asthma and rhinitis. Here we discuss a new orally active controlled-release preparation of budesonide (Entocort CR-Astra) formulated specifically for treating patients with Crohn's disease affecting the ileum and/or ascending colon. The manufacturer claims that the preparation "targets the ileum and ileocaecal area, achieving rapid results equivalent to prednisolone" with a "low level of systemic steroid side effects".

Topics: Anti-Inflammatory Agents; Budesonide; Crohn Disease; Delayed-Action Preparations; Glucocorticoids; Humans; Pregnenediones; Randomized Controlled Trials as Topic

New therapeutic measures in inflammatory bowel diseases (IBD) are either based on actual data on disease pathogenesis or on new pharmaceutic preparations of known drugs. An overshooting immune response with T cell activation in the local gut associated immune system seems to be central in the etiopathogenesis of IBD. Modulation of the antigenic load in the gut lumen by parenteral or enteral nutrition or antibiotic treatment can alter disease activity. Immunosuppressive drugs are able to decrease the overshooting immune response. Azathioprin has its clear value in chronic active steroid dependent disease courses of Crohn's disease. According to recent studies, Methotrexate seems to be active as well, however, more studies are necessary. Several studies were not able to prove that Cyclosporine is of value in the treatment of Crohn's disease. Newer preparations of aminosalicylates have shown effectiveness in both active disease and prolongation of remission in Crohn's disease in high doses. Local release formulations of steroids with high first-pass-effect as Budesonide will have their indication in subgroups of IBD patients. However, systemic steroid application is still the gold standard in active disease.

Topics: Aminosalicylic Acids; Budesonide; Colitis, Ulcerative; Crohn Disease; Glucocorticoids; Humans; Immunity, Mucosal; Immunosuppressive Agents; Lymphocyte Activation; Pregnenediones

Topics: Administration, Rectal; Anti-Inflammatory Agents; Budesonide; Colitis, Ulcerative; Crohn Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Glucocorticoids; Humans; Long-Term Care

The use of non-specific anti-inflammatory drugs such as the glucocorticoids is the foundation of medical therapy for inflammatory bowel disease. Although conventional steroid drugs are highly effective, their use is associated with the adverse effects of Cushing's syndrome. However, the therapeutic index of these drugs can be improved by chemical modification of the steroid nucleus and the use of new drug delivery systems that target the bowel wall as the pharmacokinetic compartment of interest. Budesonide is a novel glucocorticoid compound that illustrates the potential of this approach to identify effective and safe new treatments. Regional therapy for inflammatory bowel disease is an important pharmacological concept for the future development of the new glucocorticoids and other classes of drugs.

Topics: Administration, Oral; Anti-Inflammatory Agents; Budesonide; Clinical Trials as Topic; Colitis, Ulcerative; Crohn Disease; Drug Delivery Systems; Glucocorticoids; Humans; Inflammatory Bowel Diseases; Intestinal Absorption; Secondary Prevention

Topical therapy within the treatment of intestinal diseases presents realistic formulation challenges for targeted drug delivery. Some relevant oral formulation concepts are reviewed. The basic principles employed are based mainly on differences in pH and metabolic activity between the different parts of the gastrointestinal tract. A successful example of targeted drug delivery within the treatment of Crohn's disease is presented. Topical therapy for the treatment of ulcerative colitis is also discussed. Physiological variations and influence of the disease and disease status present major challenges when deciding upon a suitable formulation principle.

Topics: Administration, Oral; Administration, Rectal; Animals; Anti-Inflammatory Agents; Budesonide; Colitis, Ulcerative; Crohn Disease; Delayed-Action Preparations; Drug Delivery Systems; Humans; Intestine, Large; Intestine, Small

Due to its immunomodulatory and anti-inflammatory properties glucocorticosteroids have proved to be highly efficacious in patients with inflammatory bowel disease. However, because of the risk of side-effects, the dose and duration of therapy with systemically acting glucocorticosteroids have to be restricted. Recently the use of topically acting glucocorticosteroids has attracted great interest. Among the various topically acting glucocorticosteroids budesonide has emerged as the most promising. Budesonide is highly potent, is readily water-soluble and has low systemic bioavailability, thus reducing the risk of corticosteroid-related side-effects. When given as enema to patients with proctitis or proctosigmoiditis, the efficacy of budesonide is greater than that of placebo and equal to that of prednisolone or 5-aminosalicylic acid enemas. In an enteric-coated formulation budesonide is more effective than placebo in achieving and maintaining remission in patients with ileocecal Crohn's disease. Although corticosteroid-related side-effects are rare, some suppression of the hypothalamic-pituitary-adrenal axis may occur.

Topics: Administration, Oral; Administration, Topical; Anti-Inflammatory Agents; Budesonide; Colitis, Ulcerative; Crohn Disease; Delayed-Action Preparations; Enema; Glucocorticoids; Humans; Inflammatory Bowel Diseases; Pregnenediones

In view of a high recurrence rate of Crohn's disease after surgical resection prophylaxis is desirable. The value of various medical therapies to maintain remission after surgery has thus far only partially been established in clinical trials. Therefore, no clear guidelines are presently available. In patients with complete resection and a low risk of recurrence prophylactic treatment seems not to be necessary. In patients with a high risk of recurrence prophylactic treatment is recommended. This recommendation is supported by some clinical trials, although major trials are still ongoing. 5-Aminosalicylic acid in a daily dose of ca. 2-3 g is the primary choice for prophylaxis of recurrence. It reduces the risk of recurrence presumably by about 50%. In patients with a complicated course of the disease who have undergone several previous resections immunosuppressive treatment with azathioprine (1-2 mg/kg body weight/day) is recommended to avoid further recurrences. Conventional corticosteroids are not effective for postoperative prophylaxis. Ongoing studies evaluate the non-systemic steroid budesonide as prophylactic treatment. There is no specific nutritional therapy to prevent recurrences; however, patients are advised to avoid nutrients which they do not tolerate. When patients have a clinical relapse systemic or topical corticosteroids are the treatment of choice. In moderately active disease and in patients who refuse to take corticosteroids high dose 5-aminosalicylic acid (at least 4 g/day) may be used alternatively. In patients with chronic complicated disease azathioprine is recommended.

Topics: Aminosalicylic Acids; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Azathioprine; Budesonide; Crohn Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Immunosuppressive Agents; Mesalamine; Pregnenediones; Recurrence

Topics: Administration, Topical; Androstadienes; Anti-Inflammatory Agents; Beclomethasone; Budesonide; Clinical Trials as Topic; Colitis, Ulcerative; Crohn Disease; Fluticasone; Humans; Hydrocortisone; Prednisolone; Pregnenediones

Inflammatory bowel disease remains a serious chronic illness in children. Recent developments in the care of these patients involves both basic science research into the pathophysiology of ulcerative colitis and Crohn's disease and the development of refinements in the surgical techniques and medical therapies available as treatment options. In Crohn's disease, a new steroid analogue (budesonide) shows some promise as a possible medical treatment that would limit the devastating side effects of steroids in children. In addition, the bowel-sparing technique of strictureplasty has now been reported in children with good results. In ulcerative colitis, the surgical technique of endorectal pull-through continues to evolve with reports of the efficacy of specific pouch designs and surgical techniques. An understanding of pouchitis, the most common complication of endorectal pull-through, has focused on documenting specific alterations in the microbiology and physiology of the pouch, as well as investigating a possible link between autoantibodies and susceptibility to this complication.

Topics: Administration, Topical; Anti-Inflammatory Agents; Budesonide; Child; Colitis, Ulcerative; Crohn Disease; Glucocorticoids; Humans; Inflammatory Bowel Diseases; Postoperative Complications; Pregnenediones; Proctocolectomy, Restorative

Budesonide is a glucocorticoid with high topical activity, but low systemic bio-availability which results in reduced systemic effects in comparison with other glucocorticoids. To date, it has been evaluated for use in patients with inflammatory bowel disease when administered either orally as a controlled ileal release formulation or rectally as an enema. In comparative trials, daily treatment with budesonide enema 2 mg/100ml for 4 weeks produced endoscopic remission or improvement in 46 to 84% of patients with active distal ulcerative colitis and/or proctitis and histological remission or improvement in 45 to 68%. In general, this regimen was effective as regimens of hydrocortisone, methylprednisolone, prednisolone or mesalazine (5-amino-salicylic acid, mesalamine) enemas, but caused less suppression of plasma cortisol levels than the other glucocorticoids. Oral treatment with controlled release budesonide 9 mg/day for 8 weeks produces clinical remission in 42 to 67% of patients with active Crohn's disease of the ileum, ileocaecal region and/or ascending colon and significantly reduces Crohn's disease activity index scores compared with baseline and placebo. Results of a quality-of-life questionnaire reflected these clinical improvements. Budesonide has similar efficacy to prednisolone. Response to budesonide is maintained after dosage tapering at 8 weeks. Compared with placebo, maintenance treatment with oral budesonide 3 or 6 mg/day increases the duration of remission in patients with Crohn's disease, but does not appear to affect the 1-year relapse rate. Thus, budesonide, administered rectally to patients with distal ulcerative colitis or proctitis or orally to patients with Crohn's disease of the ileum, ileocaecal region and/or ascending colon, is a favourable option for the treatment of acute exacerbations of inflammatory bowel disease. Because of the low incidence of adverse glucocorticoid-related effects associated with oral budesonide, it may also be a useful agent for longer term maintenance therapy if further clinical trials confirm its efficacy in this indication.

Topics: Animals; Anti-Inflammatory Agents; Budesonide; Clinical Trials as Topic; Colitis, Ulcerative; Crohn Disease; Humans; Pregnenediones; Proctitis

Increased mucosa-associated E. coli are present in Crohn's disease, but their role in pathogenesis is uncertain.. To assess efficacy and safety of an antibiotic/hydroxychloroquine combination effective against E. coli inside macrophages.. Adults with moderately active disease (CDAI > 220-450 plus C reactive protein ≥ 5 mg/l and/or fecal calprotectin > 250 μg/g) were randomized to receive (open-label) oral budesonide (Entocort CR 9 mg/day 8 weeks, 6 mg/day 2 weeks, 3 mg/day 2 weeks) or oral ciprofloxacin 500 mg bd, doxycycline 100 mg bd, hydroxychloroquine 200 mg tds for 4 weeks, followed by doxycycline 100 mg bd and hydroxychloroquine 200 mg tds for 20 weeks. Primary endpoints were remission (CDAI ≤ 150) at 10 weeks, remission maintained to 24 weeks, and remission maintained to 52 weeks. Patients not responding (CDAI fall by > 70) by 10 weeks were invited to crossover onto the alternative therapy.. Fifty-nine patients were recruited across 8 sites. Including crossover, 39 patients received antibiotics/hydroxychloroquine and 39 received budesonide. At 10 weeks, 24 weeks, and 52 weeks on initial therapy, only 2/27, 2/27, and 1/27 were in remission on antibiotics/hydroxychloroquine compared with 8/32, 1/32, and 1/32 on budesonide (P = 0.092 at 10 weeks). Withdrawals by 10 weeks due to adverse events were seen in 15 receiving antibiotics/hydroxychloroquine and 6 budesonide. Results including crossover were more promising with 9/24 patients receiving antibiotics/hydroxychloroquine per protocol in remission by 24 weeks. No correlation was seen between response to antibiotics/hydroxychloroquine and ASCA/OmpC antibody status or disease location.. Overall results with this antibiotic/hydroxychloroquine combination were unimpressive, but long-term remission is seen in some patients and justifies further study.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Budesonide; Ciprofloxacin; Crohn Disease; Cross-Over Studies; Doxycycline; Drug Therapy, Combination; Enzyme Inhibitors; Humans; Hydroxychloroquine

These studies evaluated the safety and efficacy of enteric-coated budesonide for the induction and maintenance of remission of mild-to-moderate Crohn's disease (CD) in children.. The consecutive, multicenter, open-label, non-comparative studies enrolled patients aged 6-17 years. In the induction study, patients with active CD of the ileum and/or ascending colon received budesonide 9 mg or 6 mg once daily for 8 weeks; in the maintenance study, patients in remission received budesonide 6 mg once daily for 12 weeks. The primary objective was assessment of safety, including glucocorticosteroid-related side effects and serum cortisol levels. Efficacy was assessed using the Pediatric Crohn's Disease Activity Index (PCDAI), and health-related quality of life (HRQoL) using the IMPACT-III questionnaire.. In the induction study (n = 108), most adverse events were related to CD, commonly abdominal pain; possible glucocorticosteroid-related effects included acne and increased appetite but without significant weight gain. Subnormal morning cortisol levels were observed in 32 of 103 patients after 8 weeks. Budesonide reduced disease activity from baseline (mean ± standard deviation, 9.1 ± 8.5 vs. 19.1 ± 10.1, p < .001) with 58.1% of patients reaching remission (PCDAI <10); HRQoL improved (p < .001). In the maintenance study (n = 50), mean disease activity worsened (p = .047) with HRQoL unchanged (p = .33).. Budesonide treatment was generally well tolerated, although the potential for adrenal suppression was noted. Budesonide was effective for induction of remission in children with mild-to-moderate CD but not for maintaining remission (ClinicalTrials.gov identifiers: NCT01444092, NCT01453946).

Topics: Abdominal Pain; Acne Vulgaris; Adolescent; Anti-Inflammatory Agents; Budesonide; Child; Crohn Disease; Female; Humans; Male; Quality of Life; Remission Induction

The importance of efficient and safe treatment of Crohn's disease is highlighted by its chronicity. Both medical and surgical treatments have shown good results in the symptomatic control of limited ileocaecal Crohn's disease. The aim of this study was to compare medical treatment with surgical treatment of ileocaecal Crohn's disease.. Thirty-six patients from seven hospitals with primary ileocaecal Crohn's disease were randomized to either medical or surgical treatment. The medical treatment was induction of remission with budesonide and thereafter maintenance treatment with azathioprine. The surgical treatment was open ileocaecal resection. Crohn's disease activity index over time, expressed as area under the curve at 1, 3 and 5 years, was the primary endpoint. Subjective health measured with the 36-item Short Form Survey Instrument (SF36) and a visual analogue scale (VAS) were secondary endpoints.. There were no differences between the treatment groups in Crohn's disease activity index over time. General health, measured as SF36 score, was higher in patients receiving surgical treatment than in those receiving medical treatment at 1 year, but there was no corresponding difference in VAS. Due to the slow inclusion rate and changes in clinical practice, the study was t=erminated prematurely.. The study ended up being underpowered and should be interpreted with caution, but there was no clinically significant difference between the two treatment arms. Further studies are needed to address this important clinical question.

Topics: Adult; Age Factors; Anastomosis, Surgical; Area Under Curve; Azathioprine; Budesonide; Cecum; Colectomy; Crohn Disease; Female; Follow-Up Studies; Humans; Ileum; Laparotomy; Male; Middle Aged; Prospective Studies; Risk Assessment; Severity of Illness Index; Sex Factors; Statistics, Nonparametric; Sweden; Treatment Failure; Treatment Outcome; Young Adult

Oral budesonide 9 mg/day represents first-line treatment of mild-to-moderately active ileocolonic Crohn's disease. However, there is no precise recommendation for budesonide dosing due to lack of comparative data. A once-daily (OD) 9 mg dose may improve adherence and thereby efficacy.. An eight-week, double-blind, double-dummy randomised trial compared budesonide 9 mg OD versus 3mg three-times daily (TID) in patients with mild-to-moderately active ileocolonic Crohn's disease. Primary endpoint was clinical remission defined as CDAI <150 at week 8 (last observation carried forward).. The final intent-to-treat population comprised 471 patients (238 [9 mg OD], 233 [3 mg TID]). The confirmatory population for the primary endpoint analysis was the interim per protocol population (n=377; 188 [9 mg OD], 189 [3mg TID]), in which the primary endpoint was statistically non-inferior with budesonide 9 mg OD versus 3 mg TID. Clinical remission was achieved in 71.3% versus 75.1%, a difference of -3.9% (95% CI [-14.6%; 6.4%]; p=0.020 for non-inferiority). The mean (SD) time to remission was 21.9 (13.8) days versus 21.4 (14.6) days with budesonide 9 mg OD versus 3 mg TID, respectively. In a subpopulation of 122 patients with baseline SES-CD ulcer score ≥1, complete mucosal healing occurred in 32.8% (21/64) on 9 mg OD and 41.4% (24/58) on 3mg TID; deep remission (mucosal healing and clinical remission) was observed in 26.6% (17/64) and 32.8% (19/58) of patients, respectively. Treatment-emergent suspected adverse drug reactions were reported in 4.6% of 9 mg OD and 4.7% of 3 mg TID patients.. Budesonide at the recommended dose of 9 mg/day can be administered OD without impaired efficacy and safety compared to 3mg TID dosing in mild-to-moderately active Crohn's disease.

Topics: Administration, Oral; Adolescent; Adult; Aged; Budesonide; Crohn Disease; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Endoscopy, Gastrointestinal; Female; Follow-Up Studies; Glucocorticoids; Humans; Intestinal Mucosa; Male; Middle Aged; Patient Compliance; Prospective Studies; Remission Induction; Treatment Outcome; Young Adult

Current treatments for Japanese patients with active Crohn's disease have not proved optimal, and new treatment options are required. The present study therefore evaluated the efficacy and tolerability of oral budesonide in Japanese patients with mild-to-moderate active Crohn's disease.. In this multicentre, double-blind, randomized, parallel-group, Phase II study, patients (18-65 years) with baseline Crohn's Disease Activity Index (CDAI) score≥200 were randomized to once-daily (od) oral budesonide 9 mg or 15 mg, or matching placebo, for 8 weeks. Concomitant therapy with sulfasalazine or 5-aminosalicylic acid, and nutritional therapy, was allowed. The rate of remission (defined as CDAI score≤150) after 8 weeks' treatment (primary variable), health-related quality of life (assessed using the Inflammatory Bowel Disease Questionnaire [IBDQ]), and tolerability were assessed.. 77 patients were randomized and 63 completed the study. The proportion of budesonide-treated patients with remission after 8 weeks' treatment was higher compared with placebo (23.1%, 28.0%, and 11.5% for budesonide 9 mg, 15 mg, and placebo, respectively; no significant difference). The mean change from baseline to week 8 in CDAI total score (-48.0, -58.2, and -27.2, respectively) and IBDQ total score (10.8, 23.2, and 6.5, respectively) was greater for budesonide-treated patients than placebo recipients. While budesonide 9 mg and 15 mg demonstrated similar efficacy, budesonide 9 mg caused fewer drug- and glucocorticosteroid-related adverse events and less adrenal suppression.. Oral budesonide 9 mg od (for up to 8 weeks) may offer a new treatment option for Japanese patients with mild-to-moderate active Crohn's disease.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Double-Blind Method; Drug Administration Schedule; Female; Humans; Induction Chemotherapy; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Quality of Life; Severity of Illness Index; Treatment Outcome; Young Adult

Previous reports correlated microalbuminuria with disease activity in patients with Crohn's disease (CD). The aim of the present study is to determine the value of microalbuminuria as a marker for relapses in quiescent CD.. In a 1-year prospective maintenance trial with oral budesonide in patients with CD in remission, microalbuminuria was measured at randomization, after 2, 6 and 12 months, plus at the time of a relapse. The association of microalbuminuria with the course of disease was analyzed with logistic regression analysis. Time-dependent Cox regression was undertaken to study the association between microalbuminuria and relapse.. We included a total of 139 patients. At randomization, microalbuminuria was present in 8 patients. During a 1-year follow-up, 29 patients relapsed and in 11% (3/29), microalbuminuria was present during the relapse. We found no statistically significant association between microalbuminuria and relapse (odds ratio 0.92, 95% confidence interval (CI) 0.76-1.13). Time-dependent Cox regression analysis also revealed no statistical predictive value for microalbuminuria (hazard ratio 1.29, 95% CI 0.37-4.39, p = 0.68).. Microalbuminuria was moderately prevalent in quiescent CD patients, but it could not be associated with disease characteristics or the type of medication before randomization, nor as a predictor for relapses.

Topics: Adult; Albuminuria; Anti-Inflammatory Agents; Biomarkers; Budesonide; Crohn Disease; Female; Humans; Logistic Models; Male; Middle Aged; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Recurrence; Young Adult

Comparative data on budesonide vs mesalamine for the treatment of mild-to-moderately active Crohn's disease (CD) are sparse. We assessed the efficacy and safety of each therapy in patients with mildly to moderately active CD.. We performed a randomized, double-blind, double-dummy, 8-week, multicenter study in which 309 patients with mildly to moderately active CD received pH-modified-release oral budesonide (9 mg/day once daily or 3 mg/day 3 times daily) or Eudragit-L-coated oral mesalamine (4.5 g/day).. The primary efficacy variable, clinical remission (defined as Crohn's Disease Activity Index ≤150), at the final visit occurred in 69.5% (107 of 154) of patients given budesonide vs 62.1% (95 of 153) of patients given mesalamine (difference, 7.4%; 95% repeated confidence interval, -4.6% to 18.0%; P = .001 for noninferiority). Clinical remission rates did not differ significantly between the 2 budesonide groups. Treatment response, defined as Crohn's Disease Activity Index of 150 or less and/or a decrease of 70 or more (Δ70) or 100 or more (Δ100) points from baseline to final visit, did not differ significantly between patients given budesonide vs mesalamine (Δ70, P = .11; Δ100, P = .15), or between the 2 budesonide groups (Δ70, P = .38; Δ100, P = .78). No other efficacy end points differed significantly between groups. Discontinuation because of adverse events occurred in 3% and 5% of budesonide- and mesalamine-treated patients, respectively. There were no clinically relevant differences in adverse events between the 2 budesonide groups.. Budesonide (9 mg/day) was numerically, but not statistically, more effective than Eudragit-L-coated mesalamine (4.5 g/day) in patients with mildly to moderately active CD. Budesonide (9 mg/day), administered once daily, was as effective as the standard (3 times daily) regimen.

Topics: Adult; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Double-Blind Method; Female; Humans; Male; Mesalamine; Middle Aged; Remission Induction; Severity of Illness Index; Smoking; Treatment Outcome; Young Adult

There is no standard approach for the medical management of Crohn's disease (CD) during pregnancy and there is limited data regarding safety and efficacy of the treatments. Budesonide (Entocort EC, AstraZeneca) is an enteric coated locally acting glucocorticoid preparation whose pH- and time-dependent coating enables its release into the ileum and ascending colon for the treatment of mild to moderate Crohn's disease. There is no available data on the safety of using oral budesonide in pregnant patients.. We reviewed our Inflammatory Bowel Disease (IBD) center database to identify patients with CD who received treatment with budesonide for induction and/or maintenance of remission during pregnancy and describe the maternal and fetal outcomes in a series of eight mothers and their babies.. The mean age of the patients was 27.7 years. All patients had small bowel involvement with their CD. The disease pattern was stricturing in 6 patients, fistulizing in 1 and inflammatory in 1 patient. Budesonide was used at the 6 mg/day dose in 6 patients and 9 mg/day dose in 2 patients. The average treatment duration ranges from 1-8 months. There were no cases of maternal adrenal suppression, glucose intolerance, ocular side effects, hypertension or fetal congenital abnormalities.. Budesonide may be a safe option for treatment of CD during pregnancy.

Topics: Adult; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Female; Humans; Pregnancy; Pregnancy Complications; Remission Induction; Retrospective Studies; Treatment Outcome; Young Adult

The effects of azathioprine (AZA) and budesonide (BUD) on mucosal healing and histologic remission of Crohn's disease (CD) are insufficiently studied. In this prospective study we evaluated the comparative effects of AZA and BUD on endoscopic and histologic activity in patients with steroid-dependent Crohn's ileocolitis or proximal colitis who had achieved clinical remission on conventional steroids.. Patients were randomized to AZA (2.0-2.5 mg/kg a day) or BUD (6-9 mg a day) for 1 year. The study protocol included clinical examination, laboratory tests, calculation of the Crohn's Disease Activity Index (CDAI), completion of the Inflammatory Bowel Disease Questionnaire (IBDQ), at baseline and then every 2 months for 1 year. Ileocolonoscopy with regional biopsies was performed at baseline and then at the end of the study to assess mucosal healing and the histologic activity of CD.. Thirty-eight patients were randomized to AZA and 39 to BUD. At the end of the study 32 and 25 patients in the AZA and BUD groups, respectively, were in clinical remission (P = 0.07). The Crohn's Disease Endoscopic Index of Severity (CDEIS) score fell significantly only in the AZA group (P < 0.0001). Complete or near complete healing was achieved in 83% of AZA-treated patients compared with only 24% of BUD-treated patients (P < 0.0001). Histologic activity as assessed by an average histology score (AHS) fell significantly only in the AZA group (P < 0.001 versus baseline) and was significantly lower than in the BUD group at the end of the study (P < 0.001). Eight patients in the AZA group were withdrawn for adverse events (n = 6) or relapse of disease compared with 14 patients in the BUD group who were withdrawn for relapse of disease.. In patients with steroid-dependent inflammatory Crohn's ileocolitis or proximal colitis who achieve clinical remission with conventional steroids, a 1-year treatment with AZA was superior to BUD in achieving and maintaining mucosal healing and histologic remission.

Topics: Adult; Azathioprine; Budesonide; Crohn Disease; Dose-Response Relationship, Drug; Drug Resistance; Endoscopy, Gastrointestinal; Female; Follow-Up Studies; Glucocorticoids; Humans; Immunosuppressive Agents; Intestinal Mucosa; Male; Middle Aged; Prospective Studies; Remission Induction; Single-Blind Method; Treatment Outcome; Young Adult

Oral budesonide has been found to be comparable to systemic corticosteroids in mild to moderately active Crohn's disease (CD). Remission rates in pediatric studies to date have been suboptimal (47%-55%), even though patients with colonic involvement were excluded in some studies. In addition, the optimal pediatric dosing regimen has never been evaluated before.. This was a randomized, controlled, double-blind study in 70 children with mild or moderately active CD randomized to 1 of 2 groups: Group 1: Standard dose budesonide (9 mg/day) for 7 weeks followed by 6 mg budesonide daily for an additional 3 weeks. Group 2: Induction with 12 mg/day for the first month followed by the same regimen as Group 1. Outcome measures included a decrease in Pediatric Crohn's Disease Activity Index and remission rates. Patients with colonic disease were not excluded.. At week 7 a clinical response was obtained in 51.4% in Group 1 versus 74.3% in Group 2. A significant decrease in C-reactive protein was seen only in Group 2. At the end of treatment, remission was obtained in 42.9% in Group 1 versus 65.7% in Group 2 (P = 0.054). There was no significant difference in adverse events or serum cortisol.. Use of an induction dose of budesonide followed by a budesonide taper resulted in a trend to higher rates of clinical remission and a decrease in inflammation, without an increase in steroid-associated side effects. Budesonide was also useful for patients with ileocolonic disease.

Topics: Administration, Oral; Adolescent; Anti-Inflammatory Agents; Biomarkers; Budesonide; Child; Crohn Disease; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Placebos; Remission Induction; Young Adult

The Crohn's Disease Activity Index (CDAI) is used to judge efficacy in clinical trials. We explored the effect of CDAI response definitions for induction on study efficiency.. We analyzed primary CDAI data from induction studies in patients with mildly to moderately active Crohn's disease, not receiving concomitant aminosalicylates, corticosteroids, or immunomodulator therapy, and without fistulizing or stricturing complications. The 12 definitions of clinical response included: CDAI decrease from baseline by 50, 70, 100, or 150 points; decrease by 25% from baseline and by 70 or 100 points; CDAI <100 or 150 points; CDAI <150 points plus decrease by 70 or 100 points; CDAI <150 points at any time sustained for the duration of the trial; or decrease in the CDAI by 70 points for the last two consecutive visits. Response definitions were ranked according to ability to optimize the effect difference between treatment arms. The effect of time, baseline disease activity (CDAI 200-299 or > or =300 points), and previous surgical resections on response definitions were evaluated and ranked. Multivariate analysis on additional factors of age (<40 or > or =40 yr), gender and duration of disease (<2 or > or =2 yr) were performed to determine predictors of response when applied to these CDAI definitions.. Treatment effect differences in placebo-controlled studies were maximized by response definitions that incorporated either a decrease CDAI > or =70 points for the last two consecutive visits or decrease in baseline CDAI > or =100 points, and remained optimal when evaluated for the composite effect of time, baseline activity, and prior resections. A decrease in baseline CDAI > or =100 points had some advantages over a decrease CDAI > or =70 points over two visits in terms of study efficiency, as it produced a lower control response rate and was not influenced by any of the baseline factors.. Clinical trial efficiency for induction studies in patients with mildly to moderately active Crohn's disease can be improved by using either a decrease in CDAI by > or =70 points for the last two consecutive visits or a decrease in baseline CDAI by > or =100 points as the primary end point for the trial. These findings are valid for patients with ileocecal Crohn's disease not refractory to aminosalicylates, corticosteroids, immunomodulators, and biologics, and patients who do not have stricturing or penetrating complications. It is unclear if these CDAI response criteria would similarly increase study efficiency in trials that recruited patients with moderately to severely active disease, patients refractory to aminosalicylates, corticosteroids, immunomodulators, and biologics, and patients with stricturing or penetrating complications.

Topics: Budesonide; Crohn Disease; Glucocorticoids; Humans; Remission Induction; Severity of Illness Index; Treatment Outcome

In previous trials, budesonide 6 mg/day was able to prolong the time to relapse in patients with quiescent Crohn's disease and budesonide 9 mg/day was effective in active disease with limited side effects. The aim of this study was to compare the effectiveness of budesonide 9 mg vs 6 mg once daily on the maintenance of remission and occurrence of adverse events.. Double-blind, randomised trial in patients with Crohn's disease in remission. Patients were randomised to receive 6 mg/day or 9 mg/day of budesonide (Budenofalk) without concomitant treatment for Crohn's disease. Endpoints were the time to relapse and relapse rates after one year.. Seventy-six patients were randomised to 6 mg/day and 81 patients to 9 mg/day. Survival analysis showed no differences in the time to relapse. One-year relapse rates were not significantly different (6 mg group 24%; 9 mg group 19%). Any adverse event was reported in 61 and 68% of patients in the 6 mg and 9 mg groups, respectively; none of the 12 serious adverse events were drug related.. The one-year relapse rates were low and not significantly different between the group of patients treated with budesonide 6 mg vs 9 mg/day. Also, time to relapse and the number of adverse events were similar in both treatment groups.

Topics: Adult; Aged; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Dose-Response Relationship, Drug; Double-Blind Method; Female; Germany; Humans; Male; Middle Aged; Netherlands; Secondary Prevention; Survival Analysis

Budesonide is effective as initial therapy of mild to moderate Crohn's disease in adults. Superior tolerability to conventional corticosteroids might be attributed to extensive first-pass metabolism of budesonide by cytochrome P450 3A.. To evaluate biotransformation and pharmacodynamic action of budesonide in children.. Drug disposition and effects on endogenous cortisol were evaluated in 12 children with Crohn's disease (5-15 years) after first intake of 3 mg budesonide (single dose), and again after 1 week of thrice daily dosing (steady-state). The parent drug and cytochrome P450 3A-dependent metabolites were analysed in blood and urine.. Pharmacokinetic parameters of budesonide following single-dose administration (e.g. AUC(0-infinity) 7.7+/-5.1 h ng/mL, C(max) 1.8+/-1.2 ng/mL) did not change upon multiple dosing. Overall systemic elimination of budesonide reflected by clearance and half-life was not different between children and adults. After 1 week of treatment reversible adrenal suppression was observed - most pronounced in children aged below 12 years.. Disposition of oral budesonide appears to be similar between children and adults, but the doctor has to be aware of an increased risk for adrenal suppression in paediatric patients.

Topics: Administration, Oral; Adolescent; Anti-Inflammatory Agents; Budesonide; Child; Child, Preschool; Crohn Disease; Female; Humans; Hydrocortisone; Male

Budesonide is a steroid with low systemic effect and high effectiveness in the treatment of Crohn's Disease (CD). Beclomethasone dipropionate (BDP) is also a steroid with the same systemic effects, but it has been never investigated in CD.. To evaluate the effectiveness and tolerability of BDP versus budesonide in treating CD, we enrolled 30 consecutive patients affected by mild-to-moderate non-fistulizing, non-obstructive Crohn's disease (CDAI < or = 250) (13 M and 17 F, mean age: 33.4 years, range: 16-71 years) in whom this diagnosis was made for the first time. The patients were randomly treated for 8 weeks with budesonide 9 mg/day (group A, 15 patients) or with BDP 10 mg/day (group B, 15 patients).. Of group A patients, 13/14 (on intention to treat (i-t-t): 86.67%) showed response to budesonide and 10/14 (on i-t-t.: 66.66%) were in remission after 8 weeks of treatment. In group B patients, 10/14 (on i-t-t: 66.66%) showed response to BDP and 8/14 (on i-t-t: 53.33%) were in remission after 8 weeks of treatment (p<0.001). Budesonide was also faster in the time to obtain symptomatic remission (p=n.s.) and was better in improving IBDQL (p<0.05). Regarding side effects, two group A patients (6.66%) and three group B patients (10%) experienced mild-to-moderate side effects which were transitory and did not require any specific treatment or stopping the treatment.. BDP seems to be less effective than budesonide in treating CD, probably due to better the pharmacokinetic properties of budesonide.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents; Beclomethasone; Budesonide; Crohn Disease; Female; Humans; Male; Middle Aged

Osteoporosis frequently occurs in Crohn's disease, often because of corticosteroids. Budesonide as controlled release capsules is a locally acting corticosteroid with low systemic bioavailability. We investigated its effects on bone compared with prednisolone.. In 34 international centers, 272 patients with Crohn's disease involving ileum and/or colon ascendens were randomized to once daily treatment with budesonide or prednisolone for 2 years at doses adapted to disease activity. One hundred eighty-one corticosteroid-free patients had active disease (98 had never received corticosteroids, corticosteroid naive; 83 had received corticosteroids previously, corticosteroid exposed), and 90 had quiescent disease, receiving long-term low doses of corticosteroids, corticosteroid-dependent; in 1 patient, no efficacy data were obtained. Bone mineral density and fractures were assessed in a double-blinded fashion; disease activity, side effects, and quality of life were monitored.. Neither the corticosteroid-free nor the corticosteroid-dependent patients treated with budesonide differed significantly in bone mineral density from those receiving prednisolone. However, corticosteroid-naive patients receiving budesonide had smaller reductions in bone mineral density than those on prednisolone (mean, -1.04% vs -3.84%; P = .0084). Treatment-emergent corticosteroid side effects were less frequent with budesonide. Efficacy was similar in both groups.. Treatment with budesonide is associated with better preserved bone mass compared with prednisolone in only the corticosteroid-naive patients with active ileocecal Crohn's disease. In both the corticosteroid-free and corticosteroid-dependent groups, budesonide and prednisolone were equally effective for up to 2 years, but budesonide caused fewer corticosteroid side effects.

Topics: Administration, Oral; Adult; Aged; Analysis of Variance; Bone Density; Budesonide; Crohn Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Osteoporosis; Prednisolone; Probability; Reference Values; Risk Assessment; Severity of Illness Index; Single-Blind Method

To assess the efficacy and safety of budesonide capsules 6 mg daily for prolongation of time to relapse and maintenance of remission in patients with Crohn's disease (CD) affecting the ileum and/or ascending colon.. In a double-blind, placebo-controlled, multicentre trial, 110 patients with CD, who had previously achieved remission in a placebo-controlled trial of budesonide 9 mg daily, were randomly assigned to receive budesonide 6 mg once daily or placebo for 52 weeks. Primary outcome measure was time to relapse [CD activity index (CDAI) of >150 plus an increase of at least 60 points from study entry or withdrawal due to clinical deterioration].. Median time to relapse was 360 days for budesonide patients; 169 days for placebo patients (P = 0.132). No significant differences were seen between groups in relapse rates at 1 year. Budesonide was safe and well tolerated, with a similar adverse events profile to placebo.. Patients treated with budesonide 6 mg once daily had a trend towards a prolonged time to relapse and lower CDAI scores compared with patients treated with placebo, but relapse rates were not significantly different at the 1-year end point.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Double-Blind Method; Female; Humans; Male; Middle Aged; Recurrence; Severity of Illness Index; Treatment Outcome

To evaluate CDP571, a humanized monoclonal antibody to tumour necrosis factor-alpha, for the treatment of corticosteroid-dependent Crohn's disease.. Patients with corticosteroid-dependent Crohn's disease (use of prednisolone 15-40 mg/day or budesonide 9 mg/day for at least 8 weeks, a previous failed attempt to discontinue corticosteroids within 8 weeks, and Crohn's Disease Activity Index score 150 points or less) were enrolled in a 16-week, randomized, double-blind, placebo-controlled trial. The patients received intravenous CDP571 (20 mg/kg at week 0 and 10 mg/kg at week 8) or placebo. Corticosteroid therapy was decreased following a predefined schedule. The primary efficacy end-point was the percentage of patients with corticosteroid-sparing [i.e. no disease flare (Crohn's Disease Activity Index score > or =220 points) and no longer requiring corticosteroid therapy] at week 10. The major secondary efficacy end-point was corticosteroid-sparing at week 16.. Seventy-one patients received treatment. Corticosteroid-sparing was achieved by 19 of 39 (48.7%) CDP571 patients and 13 of 42 (40.6%) placebo patients (P = 0.452) at week 10, and by 18 of 39 (46.2%) CDP571 patients and seven of 32 (21.9%) placebo patients (P = 0.032) at week 16. CDP571 therapy was well-tolerated and the incidence of serious adverse events was similar to placebo.. The CDP571 was effective for corticosteroid-sparing at week 16 but not week 10, and was well-tolerated in patients with corticosteroid-dependent Crohn's disease.

Topics: Adult; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Budesonide; Crohn Disease; Double-Blind Method; Drug Administration Schedule; Female; Gastrointestinal Agents; Humans; Male; Middle Aged; Prednisolone; Quality of Life; Severity of Illness Index; Treatment Outcome; Tumor Necrosis Factor-alpha

To evaluate the efficacy and safety of oral budesonide for maintenance of remission in patients with mild to moderately active Crohn's disease (CD) of the ileum and/or ascending colon.. Four double-blind, placebo-controlled trials with identical protocols were combined according to a predetermined analysis plan. Three hundred eighty patients with CD in medically induced remission (CD activity index [CDAI]< or =150) were randomized to receive oral budesonide 3 mg, 6 mg, or placebo daily for 12 months. The primary outcome measure was time to relapse (increase in CDAI of 60 points above baseline and >150).. The median time to relapse was 268, 170, and 154 days for budesonide 6 mg, budesonide 3 mg, and placebo groups, respectively (p= 0.0072). The frequency of adverse events and glucocorticosteroid side effects were similar in all groups.. Budesonide 6 mg/day is effective for prolonging time to relapse and for significantly reducing rates of relapse at 3 and 6 months but not 12 months in patients with CD in medically induced remission.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Double-Blind Method; Female; Humans; Male; Middle Aged; Recurrence; Remission Induction; Treatment Outcome

Topics: Anti-Inflammatory Agents; Bone Density; Budesonide; Crohn Disease; Delayed-Action Preparations; Double-Blind Method; Follow-Up Studies; Glucocorticoids; Humans; Osteoporosis; Prednisolone; Treatment Outcome

The nonsystemic steroid budesonide has been used to treat active ileocecal and ileocolonic Crohn's disease (CD). This study investigated the optimal budesonide dose using a pH-dependent release formulation. The goal of treatment was the remission of CD (CDAI <150) within 6 weeks of treatment.. The study was of randomized, double-blind, dose-finding design. Patients with active CD ileocolitis without steroid pretreatment were treated with 3x2 mg ( n=39), 3x3 mg ( n=33), or 3x6 mg ( n=32) oral pH-modified released budesonide daily.. The remission rates after 6 weeks were 36% with 3x2 mg, 55% with 3x3 mg, and 66% with 3x6 mg. Significantly more patients were in remission while treated with 3x6 mg than with 3x2 mg budesonide/day. Subgroup analyses revealed that patients with high disease activity (CDAI >/= 300) or ileocolonic disease with disease manifestation distal to the transverse colon responded better to the highest budesonide dose.. Oral pH-modified released budesonide shows a dose-dependent effectiveness in patients with active ileocolonic CD. In the majority of patients 9 mg budesonide per day is sufficient. However, in patients with highly active disease or ileal disease with distal colonic manifestation higher doses of budesonide could increase the therapeutic response

Topics: Adult; Anti-Inflammatory Agents; Budesonide; Colonic Diseases; Crohn Disease; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Hydrocortisone; Ileal Diseases; Male; Treatment Outcome

Budesonide is a corticosteroid with low systemic bioavailability because of its high first-pass metabolism in the liver. In this paediatric, randomized, double-blind, double-dummy, controlled, multicentre trial, the safety and efficacy of budesonide versus prednisolone were evaluated in children with active Crohn's disease.. Forty-eight children, aged 6-16 years, with active Crohn's disease (Crohn's Disease Activity Index > 200) involving ileum and/or ascending colon were randomized to receive budesonide (9 mg/day for 8 weeks, 6 mg/day for 4 weeks) or prednisolone (1 mg/kg/day for 4 weeks, tapering for 8 weeks).. The groups were comparable for age, sex, pubertal stage, disease activity and disease duration. Mean morning plasma cortisol concentration was significantly higher in the budesonide group (200 nmol/l) than in the prednisolone group (98 nmol/l) after 8 weeks, reflecting less adrenal suppression by budesonide (difference -102 nmol/l; 95% CI -226, -52; P = 0.0028). Glucocorticosteroid side effects such as moon face and acne occurred significantly less frequently in the budesonide group. Remission (Crohn's Disease Activity Index < or = 150) was seen at 8 weeks in 12/22 (55%) patients treated with budesonide and in 17/24 (71%) patients receiving prednisolone (difference -16%; 95% CI -45,13; P = 0.25).. Significantly fewer side effects and less adrenal suppression were observed in the children receiving budesonide. Remission rates were not significantly different in the two groups. However, there was a trend for prednisolone to be more effective for inducing remission.

Topics: Adolescent; Adrenocorticotropic Hormone; Anti-Inflammatory Agents; Budesonide; Child; Crohn Disease; Double-Blind Method; Female; Humans; Hydrocortisone; Male; Prednisolone; Treatment Outcome

In Crohn's disease, antibiotics are used with variable efficacy, suggesting that some patients are more likely to respond. The aim of this study was to determine whether Crohn's patients with predominant serum antibody reactivity toward bacterial antigens OmpC and/or I2 were more likely to achieve remission with antibiotics. Patients with ileal or ileal with right-sided colonic Crohn's disease were studied in a double-blind trial of budesonide alone or budesonide plus metronidazole and ciprofloxacin. In the budesonide plus metronidazole and ciprofloxacin group, patients with OmpC/I2 predominant profiles had the highest remission rate, whereas the group with no antibody predominant profiles had the lowest rate. In the budesonide group, patients with the OmpC/I2 predominant profile had the lowest remission rate, and the no-antibody group rate was higher. Although not statistically significant, these results support further testing to determine whether predominant serum reactivity to certain bacterial antigens may be a marker for efficacious use of antibiotics.

Topics: Anti-Infective Agents; Antibodies, Antineutrophil Cytoplasmic; Antigens, Bacterial; Budesonide; Ciprofloxacin; Crohn Disease; Drug Therapy, Combination; Humans; Metronidazole; Pilot Projects; Porins; Pseudomonas fluorescens; Remission Induction; Superantigens

Budesonide has been found effective in patients with mild and moderate Crohn disease and has been found to cause fewer side effects than prednisone. The use of oral budesonide has not been prospectively evaluated in children with Crohn disease. Therefore, the authors initiated a trial to compare remission and tolerance to budesonide and prednisone in children with mild or moderately active Crohn disease.. A prospective randomized open controlled 12-week trial was carried out comparing pH modified release budesonide, 9 mg, versus prednisone, 40 mg, in children with active mild to moderate pediatric Crohn disease.. Thirty-three patients (20 boys and 13 girls; mean age, 14.3 years) enrolled and completed the study. The groups treated with budesonide and prednisone did not differ by age, onset of disease, location of disease, or disease activity. The remission rate at 12 weeks was 47% in the budesonide treatment group and 50% in the prednisone treatment group. Side effects occurred in 32% and 71% of patients treated with budesonide and prednisone, respectively (P< 0.05). Severity of cosmetic side effects was significantly lower in patients treated with budesonide (P< 0.01).. Remission rates for Crohn disease with budesonide and prednisone treatment in this study were similar. Pediatric patients treated with budesonide had significantly fewer side effects than patients treated with prednisone. Budesonide should be considered an alternative to prednisone in pediatric patients with mild to moderate disease activity.

Topics: Adolescent; Anti-Inflammatory Agents; Budesonide; Child; Crohn Disease; Female; Humans; Male; Prednisone; Prospective Studies; Treatment Outcome

To investigate the gastrointestinal pharmacokinetics of controlled-release (Entocort) and standard budesonide capsules.. Six Crohn's disease patients and eight healthy controls were given controlled-release capsules containing budesonide and an inert 111In label, following breakfast. In the patients, a standard capsule containing deuterium-labelled budesonide was given simultaneously. In the controls, on a separate occasion, the controlled-release capsules were given in the fasting state. Gastrointestinal transit was recorded by a gamma camera. Plasma budesonide and deuterium-labelled budesonide were used to estimate drug release, and urine cortisol was used to assess systemic effects.. Budesonide delivery to the ileo-colonic region was significantly greater after the intake of the controlled-release capsules [69%; 95% confidence interval (CI), 54-84] than after the standard capsules (30%; 95% CI, 15-45) (P = 0.005). Fasting had little impact on uptake. The transit and pharmacokinetics of budesonide were similar in both subject groups, although systemic availability was higher in patients (21%; 95% CI, 13-33) than in controls (12%; 95% CI, 10-14) (P = 0.009). Urinary cortisol was, however, similar in both groups.. A major fraction of budesonide is released in the ileum and throughout the colon, the intended target for the controlled-release formulation. The prandial state has little effect on budesonide uptake.

Topics: Administration, Oral; Adult; Anti-Inflammatory Agents; Budesonide; Capsules; Colon; Crohn Disease; Delayed-Action Preparations; Feces; Female; Gastrointestinal Transit; Humans; Hydrocortisone; Ileum; Intestinal Absorption; Male; Middle Aged; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Aggregated Albumin; Urinalysis

Glucocorticosteroids (GCS) are established in the treatment of active Crohn's ileitis and ileocolitis. Recently, the topical steroid budesonide was found to be effective in untreated patients with Crohn's disease (CD) causing less side effects than conventional GCS. No clinical data have been reported about the effects of switching from conventional GCS to budesonide in terms of side effects and disease activity. The primary aim of this study was to evaluate the development of side effects after switching from conventional GCS treatment to Eudragit L-coated budesonide (pH-modified release formulation) in patients taking 5-30 mg prednisolone equivalent per day for at least two weeks. In all, 178 patients with active CD (N = 88) or CD in remission during GCS treatment (N = 90) were included. Conventional GCS treatment was tapered down during a maximum of three weeks, with simultaneous intake of 3 x 3 mg budesonide. Thereafter, patients received 3 x 3 mg budesonide alone for six weeks. GCS-related side effects, disease activity and adverse events were documented at study entry and after 0, 2, 4, and 6 weeks of budesonide treatment. The percentage of patients with GCS-related side effects decreased from 65.2% (intention-to-treat-population) at entry to 43.3% (P < 0.0001) at the end of the trial. The total number of GCS-related side effects decreased significantly from 269 to 90. Of the patients who entered the study with active disease under conventional GCS therapy, 38.6% were in remission at the end of the study. Of the patients who entered the study with CD in remission, 78% stayed in remission after switching from conventinal GCS to budesonide. In conclusion, switching from conventional GCS treatment to budesonide leads to a significant reduction of GCS related side effects in patients with CD without causing rapid deterioration of the disease.

Topics: Administration, Oral; Adult; Budesonide; Crohn Disease; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Glucocorticoids; Humans; Hydrogen-Ion Concentration; Intestinal Mucosa; Male; Middle Aged; Probability; Prospective Studies; Risk Assessment; Severity of Illness Index; Statistics, Nonparametric; Treatment Outcome

In addition to their anti-inflammatory effects, steroids influence electrolyte and water transport systems in the intestinal mucosa. This study analysed the effect of the topically acting glucocorticoid budesonide on ileostomy output in patients with Crohn disease.. Oral budesonide (3 mg/three times daily for 8 days; n = 20) was compared to placebo (n = 20) in a double-blind design using matched-pair randomization according to ileal resection length in patients without detectable inflammatory activity. Under controlled hospital conditions, absolute output volumes were measured and response was defined as a reduction in intestinal output of > 25% compared to pretreatment conditions.. In the treatment group, we observed an absolute decrease in median intestinal output from 1,240 ml to 865 ml (30.2%), compared to 0.3% under placebo (from 950 ml to 947.5 ml). Response was documented in 60% (12/20 patients) in the treatment group compared to no response under placebo (P < 0.0001). While both treatment groups showed similar absolute median reductions (400 ml with ileal resection < or = 20 cm and 405 ml with ileal resection > 20 cm), the relative reduction (response rate) was lower in the subgroup of an ileal resection > 20 cm (36%) due to the greater increase in output secondary to the loss of ileum.. These data support the assumption that the absorptive capacity of the intestinal mucosa for water may be improved by topically acting steroids and suggest that this occurs independently of their anti-inflammatory effect.

Topics: Administration, Oral; Adolescent; Adult; Anti-Inflammatory Agents; Blood Platelets; Blood Sedimentation; Body Water; Budesonide; C-Reactive Protein; Crohn Disease; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Ileostomy; Intestinal Absorption; Intestinal Mucosa; Leukocytes; Male; Middle Aged; Prospective Studies; Treatment Outcome

To compare the efficacy of controlled-release budesonide capsules with that of mesalamine for maintaining remission and improving quality of life (QOL) in patients with steroid-dependent Crohn's disease.. Fifty-seven patients (25 men; mean age, 32 +/- 10.1 yr) with quiescent steroid-dependent Crohn's ileitis, ileocolitis, or colitis (Crohn's disease activity index <150) entered a prospective, investigator-blind trial. Patients were eligible for treatment with azathioprine but had not consented or had developed side effects. Patients were randomized to receive budesonide 6 mg/day (n = 29) or mesalamine 1 g 3 times/day (n = 28). Follow-up assessments were made every 2 months for up to 1 year or until relapse. At each visit, quality of life (QOL) was assessed using the Inflammatory Bowel Disease Questionnaire (IBDQ).. There were no significant differences in baseline clinical characteristics between the study groups. The 1-year relapse rate was significantly lower in the budesonide group than in the mesalamine group (55% vs. 82%; 95% confidence interval, 12.4%-41%; P = 0.045). Patients assigned to budesonide also remained in remission longer (241 +/- 114 days vs. 147 +/- 117 days; 95% confidence interval, 32.7-155.3 days; P = 0.003). Compared with mesalamine, budesonide treatment also was associated with a better QOL throughout the study (mean total IBDQ scores 165 +/- 36 vs. 182 +/- 28, respectively; 95% confidence interval, -0.4 to 34.4, P = 0.0001). This advantage was confirmed in patients' self-assessed QOL scores.. Over a 1-year period, controlled-release budesonide was significantly more effective than mesalamine for maintaining remission and improving the QOL of patients with steroid-dependent Crohn's disease.

Topics: Adult; Aged; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Crohn Disease; Female; Humans; Male; Mesalamine; Middle Aged; Prospective Studies; Quality of Life; Remission Induction; Single-Blind Method; Treatment Outcome

Budesonide controlled ileal release (CIR) capsules deliver budesonide, a glucocorticosteroid with high topical and low systemic activity, to the distal ileum and the proximal colon. In four previous controlled trials in Crohn's disease, remission rates ranged from 51% to 69%. We sought to evaluate the efficacy and safety of this drug in a population of patients in the United States with Crohn's disease.. In this multicenter, double blind, randomized trial, 200 patients in the United States with mild to moderate Crohn's disease (Crohn's Disease Activity Index [CDAI] between 200 and 450) involving the distal ileum and/or ascending colon received 9 mg of budesonide CIR once daily, 4.5 mg b.i.d., or placebos for 8 wk. The primary outcome was remission defined by a CDAI of 150 or less.. Remission was achieved in 48%, 53%, and 33% with 9 mg once daily, 4.5 mg b.i.d., and placebos, respectively, after 8 wk of treatment. Differences between the groups were not significant. The differences in mean change from baseline CDAI between the combined budesonide and placebo groups was significant (p < 0.05). There was no difference in observed adverse events between treatment groups, although a modest decrease in plasma cortisol levels was observed relative to the placebo (p < 0.01).. Treatment of symptomatic Crohn's disease with budesonide CIR capsules (9 mg daily) was safe, and remission rates were similar to those achieved in previous trials. Although the remission rate did not significantly differ from the placebo response in this study, there was a significant change in the mean CDAI from baseline in the combined treatment groups relative to the placebo.

Topics: Adult; Anti-Inflammatory Agents; Budesonide; Capsules; Crohn Disease; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; United States

Controlled ileal release budesonide and slow release mesalazine are both used to treat mild to moderate active Crohn's disease, although data show that budesonide is more effective in inducing remission. When comparing different treatment options, the effects of agents on health-related quality of life must be considered as well as efficacy. In this study, we sought to compare the effects of budesonide and mesalazine on the health-related quality of life of patients with active Crohn's disease.. The study included 182 patients with Crohn's Disease Activity Index scores between 200 and 400. Patients were randomized in a double blind, double dummy, multicenter study to receive 9 mg of budesonide, once daily (n = 93), or 2 g of mesalazine, b.i.d. (n = 89), for 16 wk. Quality of life was assessed at baseline and after 2, 4, 8, 12, and 16 wk of treatment using the Psychological General Well-Being index. In addition, a physician's global evaluation was used to assess how symptoms affected patients' normal activities.. Patients treated with budesonide experienced significantly greater improvement in Psychological General Well-Being scores than the group treated with mesalazine after 2, 8, 12, and 16 wk. All components of this index showed greater improvements in the budesonide-treated group than in the mesalazine group at 12 and 16 wk. The physician's global evaluation showed significantly greater improvements in the budesonide group than in the mesalazine group at all visits.. Budesonide (9 mg once daily) improves health-related quality of life to a greater extent than mesalazine (2 g b.i.d.) in patients with mild to moderate active Crohn's disease.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Crohn Disease; Double-Blind Method; Female; Health Status; Humans; Male; Mesalamine; Middle Aged; Quality of Life; Severity of Illness Index

Although antibiotics are frequently used to treat Crohn's disease, this practice is not supported by strong evidence from randomized trials.. We conducted a double-blind multicenter study of patients with active Crohn's disease of the ileum, right colon, or both. Patients were randomized to receive oral ciprofloxacin and metronidazole, both 500 mg twice daily, or placebo for 8 weeks. All patients received oral budesonide 9 mg once daily. The primary efficacy measure was the proportion of patients in remission at week 8.. Of the 134 patients who were randomized, 130 were evaluated for efficacy; 66 received placebo, and 64 received antibiotics. At week 8, 21 patients (33%) assigned to antibiotics were in remission as compared with 25 patients (38%) in the placebo group (P = 0.55; absolute difference, -5%; 95% confidence interval, -21% to 11%). An interaction (P = 0.025) between treatment allocation and disease location on treatment response was identified. Among patients with disease of the colon, 9 of 17 (53%) were in remission after treatment with antibiotics, compared with 4 of 16 (25%) of those who received placebo (P = 0.10). Discontinuation of therapy because of adverse events occurred in 13 of 66 (20%) patients treated with antibiotics, compared with 0 of 68 in the group who received placebo (P < 0.001).. In patients with active Crohn's disease of the ileum, the addition of ciprofloxacin and metronidazole to budesonide is an ineffective intervention, but this antibiotic combination may improve outcome when there is involvement of the colon.

Topics: Administration, Oral; Adult; Anti-Infective Agents; Budesonide; Ciprofloxacin; Colon; Crohn Disease; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Ileum; Male; Metronidazole; Remission Induction; Treatment Outcome

To study the influence of food on the systemic availability of budesonide in patients with active Crohn's disease.. Eight patients with an established diagnosis of Crohn's disease each received 9 mg budesonide controlled ileal release (CIR) capsules (Entocort capsules) orally on two separate occasions: once in a fasting state and once after a heavy breakfast. For reference, deuterium-labelled ((2)H(8)) budesonide, 0.5 mg, was given intravenously. Plasma concentrations of budesonide and (2)H(8)-budesonide were determined for 12 h, and their pharmacokinetic parameters were calculated.. Average systemic availability of budesonide during fasting conditions was 10.7%, area under the curve was 27.5 nmol/L x h and peak plasma concentration was 4.1 nmol/L. Corresponding postprandial values were 13.2%, 27.0 nmol/L x h and 3. 8 nmol/L. Food increased the mean absorption time from 4.5 to 6.8 h (P=0.0012). Body clearance of budesonide was about 25% higher after eating (P=0.0015).. Food had little influence on systemic availability and peak plasma concentrations of budesonide administered in CIR capsules. Absorption was retarded postprandially, likely due to delayed gastric emptying. Budesonide in CIR capsules can be administered at the same dose regardless of prandial status in patients with Crohn's disease.

Topics: Administration, Oral; Adult; Budesonide; Capsules; Crohn Disease; Cross-Over Studies; Female; Food; Humans; Ileum; Infusions, Intravenous; Male; Middle Aged

Steroid dependent patients with Crohn's disease are at high risk of developing glucocorticosteroid induced side effects.. We evaluated the possibility of switching from systemic steroids to budesonide (Entocort) in prednisolone/prednisone dependent patients with inactive Crohn's disease affecting the ileum and/or ascending colon.. Steroid dependent patients with a Crohn's disease activity index 200 and an increase of 60 points from baseline or withdrawal due to disease deterioration.. After one and 13 weeks without prednisolone, relapse rates were 17% and 32%, respectively, in the budesonide group, and 41% and 65% in the placebo group (95% confidence intervals for the difference in percentages -41%, -8% and -51%, -16%; p=0.004 and p<0.001, respectively). The number of glucocorticosteroid side effects was reduced by 50% by switching from prednisolone and was similar in the budesonide and placebo groups. Basal plasma cortisol increased in both groups.. The majority of patients with steroid dependent ileocaecal Crohn's disease may be switched to budesonide controlled ileal release capsules 6 mg without relapse, resulting in a sharp decrease in glucocorticosteroid side effects similar to placebo, and with an increase in plasma cortisol levels.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Hydrocortisone; Male; Middle Aged; Prednisolone; Quality of Life; Recurrence; Statistics, Nonparametric; Treatment Outcome

It may be possible to achieve more effective management of Crohn's Disease by introducing a flexible dosage regimen sensitive to patients' needs.. Comparison of the efficacy and tolerability of a fixed vs. flexible budesonide controlled ileal release treatment regimen for the prevention and management of relapse in Crohn's disease patients. Budesonide controlled ileal release is an oral formulation which delivers drug directly to disease sites in the ileum and ascending colon, by preventing more proximal release and absorption.. A randomized, double-blind comparison of a fixed dose of budesonide controlled ileal release (6 mg o.m.) and a flexible dose of budesonide controlled ileal release (3, 6 or 9 mg o.m.) for 12 months, in 143 patients in remission from ileal or ileo-caecal Crohn's Disease.. Very low rates of clinical relapse in Crohn's disease were achieved with budesonide controlled ileal release 6 mg o.m. There was no significant difference between the treatment groups with respect to the survival estimate of percentage of treatment failures (flexible group 15%, fixed group 19%; P=0.61). The average consumed dose of budesonide was comparable in both groups (5.8 mg flexible, 6.0 mg fixed). Similar proportions of patients reported adverse events (flexible 100%, fixed 97%). There were 33 serious adverse events (flexible 19, fixed 14) and 13 withdrawals due to significant adverse events (flexible 9, fixed 4).. Maintenance treatment with budesonide controlled ileal release 6 mg o.m. is well-tolerated and is associated with low rates of clinical relapse in stable Crohn's disease over 12 months. Flexible dosing remains an option for individual patients, but this study has shown no advantage over a standard fixed dosing regimen.

Topics: Adult; Aged; Algorithms; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Delayed-Action Preparations; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Severity of Illness Index; Treatment Outcome

Associations between HLA-DR genotypes and susceptibility to Crohn's disease (CD) have been reported. However, it is not known whether certain HLA-DR genotypes or IL-1ra gene polymorphism are associated with responsiveness to treatment or different clinical patterns of disease.. In a large, randomized, controlled multicentre trial, 318 patients with CD were treated with daily doses of 6, 9 or 18 mg budesonide. Patients were stratified into two groups: patients without steroid pretreatment and with active CD (CDAI > 150) and patients with conventional steroid pretreatment of < or= 30 mg prednisolone per day, which was replaced by oral budesonide within 3 weeks.. The HLA-DRB1 genotypes 1-16 and the IL-1ra gene polymorphism were examined for an association with budesonide treatment failure.. Only HLA-DR 8 was associated with treatment failure of budesonide. HLA-DR 8 is not very common. Only 17/243 patients who could be evaluated expressed this genotype, and 13 of these 17 patients did not respond to budesonide (P < 0.00067). Neither the other HLA-DR genotypes nor the IL-1ra gene polymorphism had an influence on treatment outcome of budesonide therapy. No significant association of fistulas, perianal disease, need for bowel resections, and disease localization with certain HLA-DRB1 genotypes or the IL-1ra gene polymorphism were found.. This is the first description of an association of a certain HLA-DR genotype (HLA-DR 8) with treatment failure in inflammatory bowel disease (IBD).

Topics: Adult; Aged; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Double-Blind Method; Female; Follow-Up Studies; Genotype; HLA-DR Antigens; HLA-DR Serological Subtypes; HLA-DRB1 Chains; Humans; Interleukin 1 Receptor Antagonist Protein; Male; Middle Aged; Patient Selection; Polymerase Chain Reaction; Polymorphism, Genetic; Sialoglycoproteins; Treatment Failure

Our aims were to assess the impact on health-related quality of life (HRQOL) of a controlled ileal release (CIR) formulation of budesonide in active Crohn's disease (CD) and further define the role of HRQOL, using the Inflammatory Bowel Disease Questionnaire (IBDQ), in assessing outcome in CD. A randomized trial was conducted in 258 patients with active ileal or ileocecal CD. Budesonide CIR 1.5 mg, 4.5 mg, 7.5 mg, or placebo was given b.i.d. for 8 weeks. IBDQ score changes were compared among groups. Correlations for IBDQ and Crohn's Disease Activity Index (CDAI) scores were calculated. Mean IBDQ scores improved significantly over placebo by 2 weeks in budesonide 15 mg (155+/-38; p = 0.006) and 9 mg groups (157+/-33; p = 0.0002). Bowel, systemic, social, and emotional subscores were also significantly better (p < 0.002) at 2 and 8 weeks in the 9 mg group. Improved HRQOL scores correlated well with decreased CDAI (-0.8 < r < -0.4). Average per item change in IBDQ at remission was 1.17 to 1.48. Prior surgery (p < 0.005) or current smoker (p < 0.05) status predicted poorer initial HRQOL but not response. Budesonide CIR 9 or 15 mg/day rapidly and significantly improved HRQOL in active CD.

Topics: Adult; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Dose-Response Relationship, Drug; Double-Blind Method; Emotions; Female; Humans; Male; Quality of Life; Social Behavior; Treatment Outcome

Prevention of postoperative recurrence after resection for Crohn's disease (CD) would be of great clinical benefit. The efficacy of oral budesonide for prevention of endoscopic recurrence was evaluated in patients undergoing resection for ileal or ileocecal CD.. Sixty-three patients received budesonide and 66 received placebo in a double-blind, randomized trial with parallel groups. Ileocolonoscopy, including biopsy, was performed after 3 and 12 months. Indications for surgery were fibrostenosis (78 patients), disease activity (41), and other reasons (10).. The frequency of endoscopic recurrence did not differ between the groups at 3 and 12 months. In patients with disease activity as indication for surgery, the endoscopic recurrence rate at the anastomosis was lower in the budesonide group at 3 months, although not significantly (21% vs. 47%; P = 0.11), and at 12 months (32% vs. 65%; P = 0.047). There was no such difference with respect to fibrostenosis as indication for surgery. No differences in adverse event patterns were found between the two groups.. Oral budesonide, 6 mg daily, offered no benefit in prevention of endoscopic recurrence after surgery for ileal/ileocecal fibrostenotic CD but decreased the recurrence rate in patients who had undergone surgery for disease activity.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Budesonide; Colitis; Colonoscopy; Crohn Disease; Double-Blind Method; Europe; Female; Humans; Hydrocortisone; Ileitis; Male; Middle Aged; Recurrence; Treatment Outcome

Endoscopic recurrence of Crohn's disease frequently occurs within weeks after 'curative' operation. Treatment with 3 x 1 mg oral pH-modified release budesonide was tried to prevent postoperative recurrence.. A multicentre randomized double-blind placebo-controlled trial of 1 year duration was performed.. Departments of surgery, endoscopy and pathology of three university hospitals participated in the trial.. Patients with Crohn's disease who underwent ileal and/or colonic resection and whose anastomosis was accessible to colonoscopy were admitted to the study. Of the 88 randomized patients, 83 patients were included in the efficacy analysis (budesonide n = 43, placebo n = 40). Treatment was started within 2 weeks after surgery.. Colonoscopy was performed 3 and 12 months postoperatively. The anastomosis and the adjacent bowel were evaluated by endoscopy and histology. For follow-up of the clinical course of the disease the Crohn's disease activity index (CDAI) was used.. The primary outcome variable was recurrence of Crohn's disease based on endoscopic findings. Secondary efficacy variables were histology scores, CDAI, time-to-failure and global judgement of well-being of the patient.. The recurrence rate after 1 year (endoscopic and/or clinical) was 57% (20/35) in the budesonide group and 70% (19/27) in the placebo group (n.s.). Mean time-to-failure was 196 days under budesonide and 154 days under placebo (n.s.). Median CDAI (relapse 19% vs. 28%) and global patients' judgement at the end of treatment (bad 5% vs. 15%) was slightly in favour of budesonide. One patient in each group discontinued the trial because of adverse events. Potentially steroid-related side effects were reported more frequently in the placebo than in the budesonide group (32% vs. 17%) (n.s.).. Although the effect of budesonide was altogether positive in almost all variables studied in this trial (e.g. endoscopic and histopathological score, time-to-failure, CDAI, patients' global judgement and rate of side effects), this increase in efficacy was small and the power for detecting differences versus placebo was too low to be statistically significant. According to these results, low-dose oral budesonide cannot be recommended to be used for the prevention of postoperative relapse in Crohn's disease.

Topics: Administration, Oral; Adult; Anastomosis, Surgical; Anti-Inflammatory Agents; Budesonide; Chemoprevention; Colectomy; Colonoscopy; Crohn Disease; Double-Blind Method; Female; Follow-Up Studies; Humans; Ileum; Male; Patient Satisfaction; Placebos; Postoperative Complications; Recurrence; Treatment Outcome

Topics: Administration, Topical; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Crohn Disease; Glucocorticoids; Humans; Mesalamine; Randomized Controlled Trials as Topic

The relapse rate after steroid induced remission in Crohn's disease is high.. To test whether oral pH modified release budesonide (3 x 1 mg/day) reduces the relapse rate and to identify patient subgroups with an increased risk of relapse.. In a multicentre, randomised, double blind study, 179 patients with steroid induced remission of Crohn's disease received either 3 x 1 mg budesonide (n = 84) or placebo (n = 95) for one year. The primary study aim was the maintenance of remission of Crohn's disease for one year.. Patient characteristics at study entry were similar for both groups. The relapse rate was 67% (56/84) in the budesonide group and 65% (62/95) in the placebo group. The relapse curves in both groups were similar. The mean time to relapse was 93.5 days in the budesonide group and 67.0 days in the placebo group. No prognostic factors allowing prediction of an increased risk for relapse or definition of patient subgroups who derived benefit from low dose budesonide were found. Drug related side effects were mild and no different between the budesonide and the placebo group.. Oral pH modified release budesonide at a dose of 3 x 1 mg/day is not effective for maintaining steroid induced remission in Crohn's disease.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Middle Aged; Recurrence; Remission Induction

Glucocorticosteroids are used frequently for the treatment of relapses of Crohn's disease.. To investigate the influence of the new topically active glucocorticosteroid budesonide in comparison with methylprednisolone on bone turnover in a randomized open trial.. Twenty-nine patients received either budesonide (controlled ileal release formulation) 9 mg for 10 weeks, or methylprednisolone 32 mg (equivalent to 40 mg prednisone) orally for 3 weeks with subsequent tapering.. Patients who completed the trial with methylprednisolone (n = 8) had suppression of serum osteocalcin (30.2 +/- 2.6 to 20.4 +/- 2.0 ng/mL. P < 0.01), whereas no changes in this parameter of bone synthesis were observed during budesonide treatment (n = 11) (34.8 +/- 3.1 to 33.0 +/- 3.5 ng/mL). Urinary pyridinolines and deoxypyridinolines, highly sensitive markers of bone degradation, did not change in either group.. Short-term methylprednisolone therapy impairs osteoblast activity in patients with Crohn's disease whereas budesonide does not.

Topics: Administration, Oral; Administration, Topical; Adult; Anti-Inflammatory Agents; Bone and Bones; Budesonide; Crohn Disease; Double-Blind Method; Female; Humans; Male; Methylprednisolone; Osteocalcin

Crohn's disease is often treated with glucocorticoids or mesalamine. We compared the efficacy and safety of controlled-ileal-release budesonide capsules and slow-release mesalamine tablets in patients with active Crohn's disease affecting the ileum, the ascending colon, or both.. In a double-blind, multicenter trial, we enrolled 182 patients with scores of 200 to 400 on the Crohn's Disease Activity Index (with higher scores indicating greater disease activity) and randomly assigned 93 to receive 9 mg of budesonide once daily and 89 to receive 2 g of mesalamine twice daily for 16 weeks. The primary efficacy variable was clinical remission, defined as a score of 150 or less on the Crohn's Disease Activity Index.. In the analysis of all patients who received at least one dose of study drug, the rates of remission after 8 weeks of treatment were 69 percent in the budesonide group and 45 percent in the mesalamine group (P=0.001); the respective rates after 16 weeks of treatment were 62 percent and 36 percent (P<0.001). Seventy-seven patients in the budesonide group completed the 16 weeks of treatment, as compared with 50 patients in the mesalamine group (P<0.001). The numbers of patients with adverse events were similar in the two groups, but those assigned to budesonide had fewer severe adverse events. Among patients who completed 16 weeks of treatment, the morning plasma cortisol value was normal in 67 percent of budesonide-treated patients and 83 percent of mesalamine-treated patients (P=0.06); 90 percent and 100 percent, respectively, had normal increases in cortisol in response to cosyntropin (P=0.02).. In patients with active Crohn's disease affecting the ileum, the ascending colon, or both, a controlled-ileal-release formulation of budesonide was more effective in inducing remission than a slow-release formulation of mesalamine.

Topics: Administration, Topical; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Crohn Disease; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Hydrocortisone; Male; Mesalamine; Middle Aged; Remission Induction

Budesonide is a corticosteroid with high topical anti-inflammatory activity and low systemic activity due to rapid inactivation. We have assessed the efficacy and safety of an oral controlled ileal release (CIR) preparation of budesonide for maintenance of remission in patients with ileal or ileocaecal Crohn's disease.. In a double-blind, multicentre trial, 75 patients in clinical remission (Crohn's Disease Activity Index, CDAI, < or = 150) were randomly assigned to receive placebo, budesonide 3 mg or budesonide 6 mg daily for 12 months. Trial drugs were given at a fixed dose and without concomitant medication. The primary outcome measure was relapse, defined as a CDAI > 150 together with an increase of at least 60 units from entry. A patient was also considered to have a relapse if withdrawn from the study due to clinical deterioration, whether or not a CDAI value could be calculated at that time.. There were no statistically significant differences in the relapse rate at any time-point throughout the study. By 12 months the proportion of patients having relapsed were 48, 46 and 60% in those patients treated with budesonide 6 mg, 3 mg and placebo, respectively (N.S.). Treatments were well tolerated, and the proportion of patients with suppressed adrenal function (according to predetermined criteria) were 50% (6 mg), 26% (3 mg) and 17% (placebo) (P = 0.096).. In the present study, relapse rate and time to relapse were similar in the patients treated with budesonide CIR, 6 mg daily or 3 mg daily or with placebo, throughout 12 months. This is in contrast to the two previous trials with identical design, where a significant effect of budesonide CIR in prolonging the median time to relapse was found. Possible reasons for the negative results of the present study include small sample size, and the fact that there was a high placebo response.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Disease-Free Survival; Double-Blind Method; Female; Humans; Hydrocortisone; Male; Middle Aged; Recurrence; Treatment Outcome; United Kingdom

Budesonide (BUD) is a potent steroid that undergoes extensive first-pass metabolism. BUD incorporated in a pH-dependent formulation has been proposed as an alternative treatment for Crohn's disease (CD). The aim of this study was to compare the efficacy and safety of BUD and prednisone (PRED) in the treatment of active CD involving the terminal ileum and/or the colon.. Patients with mild to moderately active CD were included in a randomized, double-blind, double-dummy controlled trial. Patients received either 9 mg BUD once daily for 8 weeks or 40 mg PRED once daily for the first 2 weeks tapered gradually to 5 mg/day by the end of the study. Disease activity, quality of life, and laboratory parameters were recorded.. One hundred patients received BUD, and 101 patients received PRED. By intention-to-treat analysis, treatment efficacy defined as Crohn's Disease Activity Index of <150 at completion was 51% and 52.5% for the BUD and PRED groups, respectively. Twice as many responded to treatment with no side effects in the BUD compared with the PRED group (30% vs. 14%) (P = 0.006). Most of the decrease in CDAI scores occurred during the first 2 weeks.. BUD is as effective as PRED in the treatment of CD involving the terminal ileum and right colon. BUD has significantly fewer steroid-related adverse reactions.

Topics: Adult; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Double-Blind Method; Female; Humans; Male; Middle Aged; Prednisone; Treatment Outcome

Budesonide, although only topically active, is effective in the treatment of Crohn's disease. This study was performed to compare the clinical efficacies of budesonide and prednisolone in relation to the activation status of circulating leukocytes.. Twenty-four patients with active Crohn's disease were randomized to treatment with either budesonide or 6-methylprednisolone. Clinical response was monitored by the Crohn's disease activity index, C-reactive protein, and orosomucoid. Expression of CD25 and CD71 on T cells and CD64 on neutrophils was determined by flow cytometry. The release of TNF-alpha and IL-1beta by peripheral blood mononuclear cells was measured by ELISA.. After 2 wk of treatment a clinical response was observed in both groups, but it was more accentuated in patients treated with prednisolone. At baseline an upregulation of CD71 and CD64, but not CD25, was found in active patients. Prednisolone significantly decreased the expression of CD64 and the release of TNF-alpha and IL-1beta, but did not alter the expression of CD25 and CD71. Budesonide treatment failed to exert any effect on circulating leukocytes.. The inability of budesonide to downregulate activated circulating leukocytes may contribute to the somewhat lower clinical efficacy of this topical steroid in the treatment of active Crohn's disease.

Topics: Adult; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Cytokines; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leukocytes; Lymphocyte Activation; Male; Methylprednisolone; Neutrophils

The use of corticosteroids in active Crohn's disease often becomes limited by side effects. Budesonide is a potent corticosteroid with low systemic bioavailability due to an extensive first pass liver metabolism.. To compare the efficacy and safety of two dosage regimens of budesonide and prednisolone in patients with active Crohn's disease affecting the ileum and/or the ascending colon.. One hundred and seventy eight patients were randomised to receive budesonide controlled ileal release (CIR) capsules 9 mg once daily or 4.5 mg twice daily, or prednisolone tablets 40 mg once daily. The treatment period was 12 weeks. The primary efficacy variable was clinical remission, defined as a Crohn's Disease Activity Index (CDAI) of 150 or less.. After eight weeks of treatment, remission occurred in 60% of patients receiving budesonide once daily or prednisolone and in 42% of those receiving budesonide twice daily (p = 0.062). The presence of glucocorticoid associated side effects was similar in all groups; however, moon face was more common in the prednisolone group (p = 0.0005). The highest frequency of impaired adrenal function, as measured by a short ACTH test, was found in the prednisolone group (p = 0.0023).. Budesonide CIR, administered at 9 mg once daily or 4.5 mg twice daily, is comparable to prednisolone in inducing remission in active Crohn's disease. The single dose administration is as promptly effective as prednisolone and represents a simpler and safer therapeutic approach, with a considerable reduction in side effects.

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Budesonide; Colitis; Crohn Disease; Delayed-Action Preparations; Double-Blind Method; Drug Administration Schedule; Female; Humans; Hydrocortisone; Ileitis; Leukocyte Count; Male; Middle Aged; Prednisolone; Pregnenediones

Budesonide is a corticosteroid with high topical anti-inflammatory activity and low systemic activity due to rapid hepatic metabolism. The efficacy and safety of an oral controlled-release preparation of budesonide for maintenance of remission was evaluated in patients with ileal or ileocecal Crohn's disease.. In a double-blind, multicenter trial, 105 patients were randomly assigned to receive placebo or budesonide at doses of 3 or 6 mg daily for 1 year. The primary outcome measure was relapse defined by a Crohn's Disease Activity Index score of > 150 and a minimum increase of 60 points.. Patients receiving 6 mg of budesonide had a median time to relapse or discontinuation of therapy of 178 days compared with 124 days in those receiving 3 mg of budesonide and 39 days in those receiving placebo. However, at 1 year, the rate of relapse in the group receiving 6 mg of budesonide was similar to the rates in the 3-mg and placebo groups. Basal plasma cortisol levels and incidence of corticosteroid-associated effects were similar in the three groups.. Oral controlled-release budesonide (6 mg/day) was well tolerated and prolonged remission in Crohn's disease of the ileum and proximal colon, but this effect was not sustained at 1-year follow-up.

Topics: Administration, Oral; Adult; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Delayed-Action Preparations; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hydrocortisone; Male; Middle Aged; Placebos; Pregnenediones; Recurrence; Treatment Outcome

To evaluate the efficacy and safety of the topical corticosteroid budesonide, given in an oral controlled release formulation for maintenance of remission in patients with ileal and ileocaecal Crohn's disease (CD).. Out of 176 patients with active CD who had achieved remission (CD activity index score < or = 150) after 10 weeks' treatment with either budesonide or prednisolone, 90 were randomised to continue with once daily treatment of 6 mg budesonide, or 3 mg budesonide or placebo for up to 12 months in a double blind, multicentre trial. Time to symptomatic relapse was calculated using Kaplan-Meier estimates. Morning plasma cortisol was measured at clinic visits and a corticotropin stimulation test was performed after three months of treatment.. Thirty two patients were allocated to the 6 mg budesonide group, 31 to the 3 mg group, and 27 to the placebo group. After three months, 19 per cent of the patients in the 6 mg group had relapsed, compared with 45 per cent in the 3 mg group and 44 per cent in the placebo group (p = 0.047). The corresponding results after 12 months was 59 per cent in the 6 mg budesonide group, 74 per cent in the 3 mg group, and 63 per cent in the placebo group (p = 0.44). The median time to relapse or discontinuation was 258 days in the 6 mg group, 139 days in the 3 mg group, and 92 days in the placebo group (p = 0.021). Mean morning plasma cortisol values increased from entry in all three groups with no statistically significant differences at 12 months. All 13 patients remaining in the placebo group after three months had a normal corticotropin stimulation response, compared with 18 of 23 patients in the 6 mg, and 19 of 21 in the 3 mg budesonide groups (p = 0.14). Acne and moon face were slightly more common in the budesonide groups.. 6 mg budesonide once daily is significantly more efficacious than placebo in prolonging time to relapse in CD, and causes only minor systemic side effects.

Topics: Administration, Oral; Adolescent; Adult; Aged; Budesonide; Crohn Disease; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Pregnenediones; Probability; Recurrence

Corticosteroids are effective in acute Crohn's disease (CD). The present study assessed the effectiveness and safety of oral pH-modified release budesonide (BUD) in patients with active CD in comparison with 6-methylprednisolone (MPred).. This was a prospective multicentre, randomized, double-blind, double-dummy study.. A total of 67 patients with active CD (CDAI > 150) were included. Patients were treated with 3 x 3 mg BUD (n = 34) or MPred (n = 33) according to a weekly tapering schedule (48-32-24-20-16-12-8 mg). The primary aim was remission of CD (CDAI < 150 and decrease by at least 60 points from baseline) after eight weeks.. Baseline demographics, disease activity and localization of CD in the small bowel and the colon were similar in both treatment groups. On an intention-to-treat basis 19/34 patients in the BUD group (55.9%) and 24/33 patients in the MPred group (72.7%) were in remission after eight weeks (P = 0.237). Therapy failed in 15/34 patients (44.1%) of the BUD group and in 9/33 patients (27.3%) of the MPred group. The mean CDAI decreased from 262 +/- 50 to 118 +/- 69 in the BUD-group and from 262 +/- 81 to 95 +/- 61 in the Mored group (P = 0.183, final CDAI BUD vs. MPred). Steroid-related side effects appeared in 28.6% of the patients in the BUD group and in 69.7% of the patients in the Mored group (P = 0.0015).. Oral pH-modified release budesonide (3 x 3 mg/day) is almost as effective as a conventional corticosteroid in patients with active CD but causes significantly less corticosteroid-related side effects.

Topics: Administration, Oral; Adult; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Delayed-Action Preparations; Double-Blind Method; Drug Administration Schedule; Female; Glucocorticoids; Humans; Hydrogen-Ion Concentration; Male; Methylprednisolone; Middle Aged; Pregnenediones; Prospective Studies; Remission Induction

To study the effect of oral budesonide and prednisolone on peripheral blood natural killer (NK) cell activity in patients with active ileocaecal Crohn's disease (Crohn's disease activity index, CDAI > or = 200).. One group of patients was treated for 10 weeks with oral budesonide (n = 9; 9 mg/day), and another group of patients for the same period with prednisolone (n = 9; 40 mg/day). Budesonide was tapered to 6 mg/day after 8 weeks and prednisolone after 2 weeks to 5 mg/day in the last week. Before treatment, and at 2, 4 and 10 weeks of treatment, natural killer cell activity was determined with a 51Cr release assay, and the number of CD16+ NK cells by Fluorescence activated cell sorter (FACS) analysis.. Budesonide, as well as prednisolone treatment, significantly decreased natural killer cell activity at weeks 2 and 4. This decrease was found to be accompanied by a similar decrease in the number of CD16+ NK cells. At 10 weeks, natural killer cell activity had almost returned to pre-treatment levels in the budesonide group and was significantly higher than pre-treatment levels in the prednisolone group. Disease activity was significantly decreased in all patients at week 2 until the end of the trial period.. Both budesonide and prednisolone treatment suppress peripheral blood natural killer cell activity of patients with active ileocaecal Crohn's disease by decreasing the numbers of CD16+ NK cells in the circulation.

Topics: Adult; Budesonide; Cell Count; Crohn Disease; Cytotoxicity Tests, Immunologic; Dose-Response Relationship, Drug; Female; Fluorescent Antibody Technique; Humans; Killer Cells, Natural; Kinetics; Male; Middle Aged; Prednisolone; Pregnenediones; Time Factors

Topics: Acute Disease; Administration, Topical; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Glucocorticoids; Humans; Pregnenediones

We recently showed that patients with active ileocecal Crohn's disease (CD) have a temporarily suppressed peripheral blood natural killer (NK) cell activity during treatment with oral budesonide or prednisolone. This suppression was caused by a decrease in the number of CD16+ NK cells in the circulation. In the present study we evaluated the contribution of cortisol in plasma to this suppressed NK cell activity. The CD patients took part in a controlled study where they received either oral budesonide or prednisolone for 10 weeks. Before treatment, and at 4 and 10 weeks of treatment, peripheral blood NK cell activity, numbers of circulating CD16+ NK cells, and plasma cortisol levels were analysed. These parameters were determined both before and 30 min after administration of adrenocorticotropic hormone (ACTH). The ACTH-induced plasma cortisol increase was accompanied by a stimulated NK cell activity, when both are suppressed by corticosteroid treatment, without changing the number of CD16+ NK cells. Therefore, a low plasma cortisol level contributes to the corticosteroid mediated NK cell suppression in active ileocecal CD.

Topics: Administration, Oral; Adrenocorticotropic Hormone; Adult; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Double-Blind Method; Female; Humans; Hydrocortisone; Killer Cells, Natural; Lymphocyte Count; Male; Middle Aged; Prednisolone; Pregnenediones; Receptors, IgG

Corticosteroids are the most efficacious drugs for inducing remission in active Crohn's disease, but their benefits are frequently offset by serious side effects. Budesonide is a corticosteroid with high topical antiinflammatory activity but low systemic activity because of extensive hepatic metabolism. We investigated the efficacy and safety of an oral controlled-ileal-release preparation of budesonide in patients with active Crohn's disease involving the ileum or ileum and proximal colon.. In a double-blind, multicenter trial, 258 patients were randomly assigned to receive placebo or one of three doses of budesonide--3, 9, or 15 mg daily. The primary outcome measure was clinical remission, as defined by a score of 150 or less on the Crohn's disease activity index.. After eight weeks of treatment, remission occurred in 51 percent of the patients in the group receiving 9 mg of budesonide (95 percent confidence interval, 39 to 63 percent), 43 percent of those receiving 15 mg (95 percent confidence interval, 31 to 55 percent), and 33 percent of those receiving 3 mg (95 percent confidence interval, 21 to 44 percent), as compared with 20 percent of those receiving placebo (P < 0.001, P = 0.009, and P = 0.13, respectively). Improvements in the quality of life, as measured by the patients' responses to the inflammatory bowel disease questionnaire, paralleled these remission rates. Location of disease, prior surgical resection, and previous use of corticosteroids did not affect the outcome. A total of 119 patients (46 percent) were withdrawn from the study before the trial ended, 96 because of insufficient therapeutic effects, 13 because of adverse reactions, and 10 because of noncompliance. Budesonide caused a dose-related reduction in basal and corticotropin-stimulated plasma cortisol concentrations but was not associated with clinically important corticosteroid-related symptoms or other toxic effects.. In an eight-week trial, an oral controlled-release preparation of budesonide at an optimal daily dose of 9 mg was well tolerated and effective against active Crohn's disease of the ileum and proximal colon.

Topics: Administration, Oral; Adolescent; Adult; Aged; Budesonide; Crohn Disease; Delayed-Action Preparations; Double-Blind Method; Female; Glucocorticoids; Humans; Hydrocortisone; Male; Middle Aged; Patient Compliance; Pregnenediones; Remission Induction; Treatment Outcome

Patients with active Crohn's disease are often treated with corticosteroids, but the treatment has many side effects. Budesonide is a potent, well-absorbed corticosteroid, but because of a high rate of first-pass metabolism in the liver, its systemic bioavailability is low.. We conducted a randomized, double-blind, 10-week trial comparing the efficacy and safety of an oral controlled-release form of budesonide with the efficacy and safety of prednisolone in 176 patients with active ileal or ileocecal Crohn's disease (88 patients in each treatment group). The dose of budesonide was 9 mg per day for eight weeks and then 6 mg per day for two weeks. The dose of prednisolone was 40 mg per day for two weeks, after which it was gradually reduced to 5 mg per day during the last week.. At 10 weeks, 53 percent of the patients treated with budesonide were in remission (defined as a score < or = 150 on the Crohn's disease activity index), as compared with 66 percent of those treated with prednisolone (P = 0.12). The mean score on the Crohn's disease activity index decreased from 275 to 175 in the budesonide group and from 279 to 136 in the prednisolone group (P = 0.001). Corticosteroid-associated side effects were significantly less common in the budesonide group (29 vs. 48 patients, P = 0.003). Two patients in the prednisolone group had serious complications (one had intestinal perforation and one an abdominal-wall fistula). The mean morning plasma cortisol concentration was significantly lower in the prednisolone group than in the budesonide group after 4 weeks (P < 0.001) and 8 weeks (P = 0.02) of therapy, but not after 10 weeks.. Among patients with active Crohn's disease, both controlled-release budesonide and prednisolone are effective in inducing remission. In this trial, prednisolone reduced scores on the Crohn's disease activity index more, whereas with budesonide there were fewer glucocorticoid-associated side effects and less suppression of pituitary-adrenal function.

Topics: Adult; Budesonide; Crohn Disease; Delayed-Action Preparations; Double-Blind Method; Female; Glucocorticoids; Humans; Hydrocortisone; Male; Prednisolone; Pregnenediones; Remission Induction; Treatment Outcome

We studied the efficacy and safety of the topically acting steroid budesonide in an oral preparation for controlled ileal release in an open, uncontrolled trial. Twenty-one patients with active Crohn's disease localized to the distal ileum, ileocaecal region or ascending colon, entered the trial. The median age was 36 years and the median duration of Crohn's disease was 8 years. The patients received budesonide, in a controlled ileal release preparation, in a dose of 3 mg t.d.s. for 12 weeks, followed by a reduction to 2 mg t.d.s. for 6 weeks and finally to 1 mg t.d.s. for an additional 6 weeks. Primary variables were the modified Crohn's disease activity index (mCDAI), laboratory parameters and plasma cortisol levels. The mean mCDAI at entry was 268 (+/- 71 s.d.), dropping to 146 (+/- 91 s.d.) after 4 weeks of treatment and to 122 (+/- 87 s.d.) after a total of 12 weeks on 3 mg t.d.s. (P < 0.001). Following dose reduction, the mean mCDAI increased after 18 and 24 weeks of treatment. The erythrocyte sedimentation rate also fell significantly during the study period. Eighteen patients responded favourably during the first 12-week treatment period, and 13 completed the trial. Seven patients were withdrawn due to failure of treatment after reduction of dose, and four of those were treated surgically. No serious side-effects or significant corticosteroid-related side-effects occurred. The mean plasma cortisol levels decreased, but remained within normal range. Four patients were markedly suppressed on the highest dose of budesonide.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Administration, Topical; Adult; Anti-Inflammatory Agents; Blood Sedimentation; Budesonide; Crohn Disease; Delayed-Action Preparations; Dose-Response Relationship, Drug; Female; Humans; Hydrocortisone; Male; Middle Aged; Pilot Projects; Pregnenediones

Vedolizumab (VDZ), a gut-selective anti-lymphocyte trafficking integrin antibody, is effective in treating patients with moderately to severely active Crohn's disease (CD). In this study, we examined the real-world effectiveness and safety of induction therapy using VDZ alone or in combination with budesonide (VDZ + BUD) among patients with CD in Belgium, Israel, and Switzerland.. This retrospective chart review analysis included adult patients with moderately to severely active CD who started induction treatment with VDZ or VDZ + BUD (January 2015 through January 2019). The primary objective of this study was to assess the effectiveness in terms of clinical remission of VDZ alone or VDZ + BUD using patient-reported outcomes (PRO) of abdominal pain (AP) and/or loose stool frequency (LSF) (PRO-2) at weeks 0, 2, 6, 10, and 14. Regression models were used to assess differences and associations between the treatment groups.. Overall, 123 patients were included (VDZ, n = 73; VDZ + BUD, n = 50). Clinical remission rates at week 14 were 71.4% (50/70) and 68.0% (34/50) with VDZ and VDZ + BUD, respectively. Mean percentage change in AP and LSF from baseline to week 14 was comparable between the groups. Median (95% confidence interval [CI]) time to clinical remission was 91 [70.0-98.0] and 95 [70.0-98.0] days, respectively. One patient in each group discontinued VDZ and 68.0% of patients in the VDZ + BUD group discontinued BUD before week 14. The rates of overall adverse events were similar between the groups (VDZ, 23.3%; VDZ + BUD, 26.0%).. In this retrospective study, VDZ alone and VDZ + BUD showed similar high remission rates in patients with moderately to severely active CD. Prospective randomized studies are needed to conclude on the role of combining VDZ with BUD.. Not applicable.

Topics: Adult; Antibodies, Monoclonal, Humanized; Budesonide; Crohn Disease; Diarrhea; Europe; Gastrointestinal Agents; Humans; Prospective Studies; Remission Induction; Retrospective Studies; Treatment Outcome

The treatment of chronic pouchitis remains a challenge due to the paucity of high-quality studies. We aimed to provide guidance for clinicians on the appropriateness of medical and surgical treatments in chronic pouchitis.. Appropriateness of medical and surgical treatments in patients with chronic pouchitis was considered in 16 scenarios incorporating presence/absence of four variables: pouchitis symptoms, response to antibiotics, significant prepouch ileitis, and Crohn's disease (CD)-like complications (i.e., stricture or fistula). Appropriateness of permanent ileostomy in patients refractory to medical treatments was considered in eight additional scenarios. Using the RAND/UCLA appropriateness method, international IBD expert panelists rated appropriateness of treatments in each scenario on a 1-9 scale.. Chronic antibiotic therapy was rated appropriate only in asymptomatic antibiotic-dependent patients with no CD-like complications and inappropriate in all other scenarios. Ileal-release budesonide was rated appropriate in 6/16 scenarios including patients with significant prepouch ileitis but no CD-like complications. Probiotics were considered either inappropriate (14/16) or uncertain (2/16). Biologic therapy was considered appropriate in most scenarios (14/16) and uncertain in situations where significant prepouch ileitis or CD-like complications were absent (2/16). In patients who are refractory to all medications, permanent ileostomy was considered appropriate in all scenarios (7/8) except in asymptomatic patients with no CD-like complications.. In the presence of significant prepouch ileitis or CD-like complications, chronic antibiotics and probiotics are inappropriate. Biologics are appropriate in all patients except in asymptomatic patients with no evidence of complications. Permanent ileostomy is appropriate in most medically refractory patients.

Topics: Anti-Bacterial Agents; Biological Products; Budesonide; Crohn Disease; Graft vs Host Disease; Humans; Ileitis; Pouchitis

Topics: Budesonide; Crohn Disease; Gastrointestinal Agents; Humans; Remission Induction

BACKGROUND There is a recognized association between inflammatory bowel disease (IBD) and hepatobiliary autoimmune disease, particularly primary sclerosing cholangitis (PSC). There have been fewer reported cases of IBD and primary biliary cholangitis (PBC), which is treated with ursodeoxycholic acid (UDCA). This report presents the case of a 60-year-old woman with PBC who was diagnosed with Crohn's ileitis after suspension of UDCA treatment. CASE REPORT A 66-year-old female patient with PBC was admitted to our department for irrepressible chronic diarrhea and recurrent abdominal pain. PBC was diagnosed on the basis of serological data: chronic (>6 months) increase in alkaline phosphatase (ALP) associated with positivity for specific anti-nuclear antibodies (sp100 and gp210), without requiring a liver biopsy and a magnetic resonance cholangiopancreatography to rule out PSC. Given the intolerance and non-responsiveness according to the Toronto criteria (ALP <1.67 times the normal limit after 2 years) to UDCA at 15 mg/kg/day, an oral monotherapy treatment using obeticholic acid at 5 mg/day was prescribed. The patient complained of abdominal pain and upper gastrointestinal symptoms. The endoscopic/histologic and radiologic examinations supported the diagnosis of Crohn's ileitis. Given the potential benefits to PBC patients of what is described as off-label therapy, budesonide at a dosage of 9 mg/day p.o. was also administered. One month after discharge, an improvement was observed both in the cholestasis indices and in gastrointestinal symptoms. CONCLUSIONS This report presents a case of PBC in which the patient was diagnosed with Crohn's ileitis after cessation of treatment with UDCA, and highlights the importance of recognizing the association between autoimmune hepatobiliary disease and IBD.

Topics: Abdominal Pain; Aged; Alkaline Phosphatase; Autoimmune Diseases; Budesonide; Crohn Disease; Female; Humans; Ileitis; Inflammatory Bowel Diseases; Liver Cirrhosis, Biliary; Middle Aged; Ursodeoxycholic Acid

Drug product performance might be affected in Crohn's disease (CD) patients compared to healthy subjects due to pathophysiological changes. Since a low number of clinical studies is performed in this patient population, physiologically-based pharmacokinetic (PBPK) models with integrated results from biorelevant in vitro dissolution studies could be used to assess differences in the bioavailability of drugs. Using this approach, budesonide was used as model drug and its performance in healthy subjects and CD patients was predicted and compared against observed pharmacokinetic data. The in vitro release tests, under healthy versus CD conditions, revealed a similar extent of drug release from a controlled-release budesonide formulation in the fasted state, whereas in the fed state a lower extent was observed with CD. Differences in the physiology of CD patients were identified in literature and their impact on budesonide performance was investigated with a PBPK model, revealing the highest impact on the simulated bioavailability for the reduced hepatic CYP3A4 enzyme abundance and lower human serum albumin concentration. For CD patients, a higher budesonide exposure compared to healthy subjects was predicted with a PBPK population adapted to CD physiology and in agreement with observed pharmacokinetic data. Budesonide performance in the fasted and fed state was successfully predicted in healthy subjects and CD patients using PBPK modeling and in vitro release testing. Following this approach, predictions of the direction and magnitude of changes in bioavailability due to CD could be made for other drugs and guide prescribers to adjust dosage regimens for CD patients accordingly.

Topics: Budesonide; Computer Simulation; Crohn Disease; Healthy Volunteers; Humans; Models, Biological; Solubility

Changes in absorptive capacity and first-pass metabolism in the small intestine affect oral drug bioavailability. Characterization of such changes as a consequence of inflammation is important for developing physiologically-based pharmacokinetic (PBPK) models for inflammatory bowel disease. We sought to elucidate the impact of small intestinal Crohn's disease (CD) on villous length and CYP3A4 expression in children. Freshly frozen duodenal and terminal ileum (TI) biopsies from 107 children (1-19 years) with and without CD were evaluated for active inflammation. Villous length and CYP3A4 mRNA/protein expression were compared among regions of active and inactive inflammation in CD and controls. A twofold reduction in villous length was observed in inflamed duodena and ilia of children with CD, but in the absence of regional inflammation, villi in CD were comparable in length to controls. Expression of CYP3A4 mRNA correlated significantly with villous length in the TI (P = 0.0003), with a trend observed in the duodenum that did not reach statistical significance. In the presence of active inflammation, a significant decrease in CYP3A protein expression was confirmed in the duodenum, where protein expression also correlated significantly with villous length across diagnoses (P < 0.0001). Our findings suggest that previous observations of decreased CYP3A4 expression and function in inflamed intestine may not be due solely to downregulation by inflammatory cytokines, but also to villous blunting and subsequent loss of surface area for protein expression. This information is relevant for PBPK model development and could aid with dose adjustment decisions for oral CYP3A4 substrates administered during CD flare (e.g., budesonide).

Topics: Administration, Oral; Adolescent; Anti-Inflammatory Agents; Biological Availability; Biopsy; Budesonide; Case-Control Studies; Child; Child, Preschool; Crohn Disease; Cytochrome P-450 CYP3A; Dose-Response Relationship, Drug; Duodenum; Female; Humans; Ileum; Infant; Intestinal Absorption; Intestinal Mucosa; Male; Models, Biological; Young Adult

A 14-year-old girl presented to the ophthalmology clinic with progressive diminution of vision, redness, pain and photophobia in both eyes for the last 1 month. She had abdominal pain, diarrhoea and weight loss during that period. Ocular examination revealed features of anterior uveitis, vitritis and retinal vasculitis. In view of gastrointestinal symptoms, abdominal imaging was done, which showed multiple enhancing bowel wall thickening with skip lesions in the terminal ileum and ascending colon. Colonoscopy showed ulcers in the ascending colon, caecum and terminal ileum. Histopathology revealed microgranulomas in lamina propria and submucosal granulomas suggestive of Crohn's disease. The patient was started on topical steroid eye drops and oral budesonide and mesalazine. Her vision improved after 3 weeks and bowel symptoms attained remission after 8 weeks, and at present, she is doing well.

Topics: Abdominal Pain; Adolescent; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Colonoscopy; Crohn Disease; Female; Humans; Mesalamine; Panuveitis; Tomography, Optical Coherence

Inflammatory bowel disease (IBD) is commonly treated with corticosteroids and anti-tumor necrosis factor (TNF) drugs; however, medications have well-described adverse effects. Prior work suggests that anti-TNF therapy may reduce all-cause mortality compared with prolonged corticosteroid use among Medicare and Medicaid beneficiaries with IBD.. To examine the association between use of anti-TNF or corticosteroids and all-cause mortality in a national cohort of veterans with IBD.. This cohort study used a well-established Veteran's Health Administration cohort of 2997 patients with IBD treated with prolonged corticosteroids (≥3000-mg prednisone equivalent and/or ≥600 mg of budesonide within a 12-month period) and/or new anti-TNF therapy from January 1, 2006, to October 1, 2015. Data were analyzed between July 1, 2019, and December 31, 2020.. Use of corticosteroids or anti-TNF.. The primary end point was all-cause mortality as defined by the Veterans Health Administration vital status file. Marginal structural modeling was used to compare associations between anti-TNF therapy or corticosteroid use and all-cause mortality.. A total of 2997 patients (2725 men [90.9%]; mean [SD] age, 50.0 [17.4] years) were included in the final analysis, 1734 (57.9%) with Crohn disease (CD) and 1263 (42.1%) with ulcerative colitis (UC). All-cause mortality was 8.5% (n = 256) over a mean (SD) of 3.9 (2.3) years' follow-up. At cohort entry, 1836 patients were new anti-TNF therapy users, and 1161 were prolonged corticosteroid users. Anti-TNF therapy use was associated with a lower likelihood of mortality for CD (odds ratio [OR], 0.54; 95% CI, 0.31-0.93) but not for UC (OR, 0.33; 95% CI, 0.10-1.10). In a sensitivity analysis adjusting prolonged corticosteroid users to include patients receiving corticosteroids within 90 to 270 days after initiation of anti-TNF therapy, the OR for UC was statistically significant, at 0.33 (95% CI, 0.13-0.84), and the OR for CD was 0.55 (95% CI, 0.33-0.92).. This study suggests that anti-TNF therapy may be associated with reduced mortality compared with long-term corticosteroid use among veterans with CD, and potentially among those with UC.

Topics: Adult; Aged; Aged, 80 and over; Budesonide; Cause of Death; Cohort Studies; Colitis, Ulcerative; Crohn Disease; Female; Glucocorticoids; Humans; Male; Middle Aged; Prednisone; Tumor Necrosis Factor Inhibitors; United States; United States Department of Veterans Affairs; Veterans Health; Young Adult

Pouchitis treatment is a complex entity that requires a close medical and surgical relationship. The elective treatment for acute pouchitis is antibiotics. After a first episode of pouchitis it is recommended prophylaxis therapy with a probiotic mix, nevertheless it is not clear the use of this formulation for preventing a first episode of pouchitis after surgery. First-line treatment for chronic pouchitis is an antibiotic combination. The next step in treatment should be oral budesonide. Selected cases of severe, chronic refractory pouchitis may benefit from biologic agents, and anti-TNF α should be recommended as the first option, leaving the new biologicals for multi-refractory patients. Permanent ileostomy may be an option in severe refractory cases to medical treatment.

Topics: Acute Disease; Advisory Committees; Algorithms; Anti-Bacterial Agents; Biological Products; Budesonide; Chronic Disease; Ciprofloxacin; Colitis, Ulcerative; Crohn Disease; Drug Resistance; Enema; Humans; Ileostomy; Immunosuppressive Agents; Metronidazole; Postoperative Complications; Pouchitis; Probiotics; Randomized Controlled Trials as Topic; Secondary Prevention; Spain

Patients with Crohn's disease (CD) are at risk for short bowel syndrome (SBS). We investigated independent predictors for SBS in these patients to allow the development of preventive strategies.. All adult patients seen at the Nancy University hospital for CD or SBS between 2012 and 2019 were eligible for inclusion in this case-control study. Each CD patient with SBS was matched to 9 controls.. 410 CD patients were included (369 without SBS and 41 with SBS). Subjects with SBS underwent significantly more bowel resections (median value of 3 vs 1, p<0.0001) and median time before the first surgery was not different than controls (6 vs 4 years, p=0.59). A higher need for parenteral support was found in end-jejunostomy SBS than in jejunocolic and jejunoileal SBS (70.6% vs 25% and 0%, p=0.0031). Montreal B1 behavior (OR 0.02, CI 95% 0-0.08) and budesonide treated-patients (OR=0.03, CI 95% 0.003-0.2) were at lower risk of SBS, while IV steroid treated-patients were at higher risk (OR=8.5, CI 95% 3.0-24.9).. Montreal B1 behavior, IV steroids and budesonide use are influencing predictors for this complication. These predictors should be assessed in daily clinical practice to prevent SBS occurrence.

Topics: Adult; Budesonide; Case-Control Studies; Crohn Disease; Female; Humans; Intestine, Small; Jejunostomy; Male; Parenteral Nutrition; Prognosis; Regression Analysis; Short Bowel Syndrome; Steroids; Young Adult

Topics: Administration, Oral; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Delayed-Action Preparations; Humans

Topics: Adalimumab; Azathioprine; Budesonide; Colectomy; Colitis; Crohn Disease; Gastric Fistula; Humans; Ileitis; Immunosuppressive Agents; Intestinal Fistula; Male; Middle Aged; Pancreatic Fistula; Tomography, X-Ray Computed; Treatment Outcome

Topics: Adalimumab; Anti-Bacterial Agents; Anti-Inflammatory Agents; Budesonide; Colonoscopy; Colostomy; Constriction, Pathologic; Crohn Disease; Disease Management; Embolization, Therapeutic; Endoscopy, Digestive System; Esophageal Diseases; Esophagitis; Female; Gastric Artery; Gastrointestinal Hemorrhage; Hematemesis; Humans; Infliximab; Magnetic Resonance Imaging; Middle Aged; Omeprazole; Proton Pump Inhibitors; Rectovaginal Fistula; Recurrence; Sigmoid Diseases; Tumor Necrosis Factor Inhibitors

Crohn's disease (CD) is a lifelong illness with substantial morbidity, although new therapies and treatment paradigms have been developed. We provide guidance for treatment of ambulatory patients with mild to severe active luminal CD.. We performed a systematic review to identify published studies of the management of CD. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a group of specialists.. The consensus includes 41 statements focused on 6 main drug classes: antibiotics, 5-aminosalicylate, corticosteroids, immunosuppressants, biologic therapies, and other therapies. The group suggested against the use of antibiotics or 5-aminosalicylate as induction or maintenance therapies. Corticosteroid therapies (including budesonide) can be used as induction, but not maintenance therapies. Among immunosuppressants, thiopurines should not be used for induction, but can be used for maintenance therapy for selected low-risk patients. Parenteral methotrexate was proposed for induction and maintenance therapy in patients with corticosteroid-dependent CD. Biologic agents, including tumor necrosis factor antagonists, vedolizumab, and ustekinumab, were recommended for patients failed by conventional induction therapies and as maintenance therapy. The consensus group was unable to clearly define the role of concomitant immunosuppressant therapies in initiation of treatment with a biologic agent.. Optimal management of CD requires careful patient assessment, acknowledgement of patient preferences, evidence-based use of existing therapies, and thorough assessment to define treatment success.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal, Humanized; Azathioprine; Budesonide; Canada; Crohn Disease; Gastroenterology; Gastrointestinal Agents; Glucocorticoids; Humans; Immunosuppressive Agents; Induction Chemotherapy; Maintenance Chemotherapy; Mesalamine; Methotrexate; Prednisolone; Societies, Medical; Sulfasalazine; Treatment Outcome; Tumor Necrosis Factor Inhibitors; Ustekinumab

Topics: Acute Disease; Adult; Azathioprine; Budesonide; Crohn Disease; Drug Substitution; Humans; Immunosuppressive Agents; Male; Mercaptopurine; Sialadenitis; Submandibular Gland; Ultrasonography

Topics: Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Crohn Disease; Humans; Mesalamine; Remission Induction

To evaluate how Italian gastroenterologists use corticosteroids in clinical practice for the treatment of Crohn's disease (CD) and ulcerative colitis (UC).. All members of the Italian Group for Inflammatory Bowel Disease (IG-IBD) were invited to fill in a web-based questionnaire.. 131/448 (29.2%) members completed the survey. In mild-to-moderate UC and CD relapses, low-bioavailability steroids (LBS) are first-line therapy for 37% and 42% of clinicians, respectively. In case of failure, immediate step-up to biologics or immunosuppressants is considered by 23% and 29%. Regarding conventional corticosteroids (CCS), a fixed starting dose is prescribed by 50%, and a weight-based dose by 22%. Tapering is started after 7-10days by 41% and after 14days by 32%. The preferred tapering schedule is 5mg/week. In case of CCS failure, 47% switch to parenteral steroids before considering shifting to different drug classes. In case of symptoms recurrence during tapering, 14% re-increase the dose and try tapering again. Before prescribing steroids, 72% do not prescribe any specific evaluation whereas during treatment some evaluation is performed by 85%. Vitamin D and calcium supplements are routinely prescribed along with steroids by 38%.. Several discrepancies and some deviation from the available guidelines were recorded among Italian gastroenterologists regarding corticosteroids use in IBD patients.

Topics: Administration, Intravenous; Administration, Oral; Adrenal Cortex Hormones; Adult; Anti-Inflammatory Agents; Beclomethasone; Biological Availability; Biological Products; Budesonide; Calcium; Colitis, Ulcerative; Crohn Disease; Dietary Supplements; Drug Administration Schedule; Health Care Surveys; Humans; Immunosuppressive Agents; Italy; Middle Aged; Practice Patterns, Physicians'; Prednisone; Recurrence; Severity of Illness Index; Vitamin D

T cells are key players in the chronic intestinal inflammation that characterises Crohn's disease. Here we aim to map the intestinal T-cell receptor [TCR] repertoire in patients with Crohn's disease, using next-generation sequencing technology to examine the clonality of the T-cell compartment in relation to mucosal inflammation and response to therapy.. Biopsies were taken from endoscopically inflamed and uninflamed ileum and colon of 19 patients with Crohn's disease. From this cohort, additional biopsies were taken after 8 weeks of remission induction therapy from eight responders and eight non-responders. Control biopsies from 11 patients without inflammatory bowel disease [IBD] were included. The TCRβ repertoire was analysed by next-generation sequencing of biopsy RNA.. Both in Crohn's disease patients and in non-IBD controls, a broad intestinal T-cell repertoire was found, with a considerable part consisting of expanded clones. Clones in Crohn's disease were more expanded [p = 0.008], with the largest clones representing up to as much as 58% of the total repertoire. There was a substantial overlap of the repertoire between inflamed and uninflamed tissue and between ileum and colon. Following therapy, responders showed larger changes in the T-cell repertoire than non-responders, although a considerable part of the repertoire remained unchanged in both groups.. The intestinal T-cell repertoire distribution in Crohn's disease is different from that in the normal gut, containing profoundly expanded T-cell clones that take up a large part of the repertoire. The T-cell repertoire is fairly stable regardless of endoscopic mucosal inflammation or response to therapy.

Topics: Adalimumab; Adult; Anti-Inflammatory Agents; Biopsy; Budesonide; C-Reactive Protein; Case-Control Studies; Clone Cells; Colon; Crohn Disease; Female; Gastrointestinal Agents; Humans; Ileum; Inflammation; Infliximab; Male; Middle Aged; Receptors, Antigen, T-Cell; Severity of Illness Index; T-Lymphocytes; Young Adult

Changes in medical therapy and surgery might have influenced the natural history of Crohn's disease (CD). Our aim was to explore the short-term outcome of CD and to specifically assess trends in disease phenotype, medications and surgery in the first five years from diagnosis.. A population-based cohort comprising 472 CD patients diagnosed within the primary catchment area of Örebro University Hospital 1963-2005 were identified retrospectively and described. Data on medication, surgery, progression in disease location and behavior, were extracted from the medical records. Patients were divided into three cohorts based on year of diagnosis.. The proportion of patients with complicated disease behavior five years after diagnosis decreased from 54.4% (95%CI, 43.9-65.6) to 33.3% (27.4-40.0) in patients diagnosed 1963-1975 and 1991-2005, respectively (p = 0.002), whereas the proportion of patients progressing to complicated disease behavior was stable among those with non-stricturing, non-penetrating disease at diagnosis (p = 0.435). The proportion of patients undergoing surgery decreased from 65.8% (55.4-76.0) to 34.6% (28.6-41.5) in patients diagnosed 1963-1975 and 1991-2005, respectively (p < 0.001). The reduction in surgery preceded an increased use of immunomodulators and was explained by a decrease in surgery within three months from diagnosis (p = 0.001).. We observed a striking decrease in complicated disease behavior and surgery five years after CD diagnosis, the latter largely due to a decrease in early surgery. Our findings suggest that the introduction of new treatments alone does not explain the reduction in surgery rates, the increasing proportion of patients with inflammatory disease at diagnosis also play an important role.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Aminosalicylic Acid; Anti-Inflammatory Agents; Budesonide; Child; Child, Preschool; Crohn Disease; Digestive System Surgical Procedures; Disease Progression; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Phenotype; Retrospective Studies; Sweden; Time Factors; Young Adult

Patients with inflammatory bowel disease (IBD), particularly those on immunosuppressive medications, suffer a high incidence of, and worse clinical outcomes relating to, herpes zoster (HZ) reactivation. We report on the presentation and management of a patient with Crohn's disease who developed severe perianal HZ after starting azathioprine and oral budesonide treatment. The zoster vaccine may prevent such zoster reactivation in patients with IBD. The zoster vaccine is effective in decreasing the risk of HZ in older adults but its role in younger adults and those with IBD has not been tested prospectively. A review of the potential risks and benefits of this live vaccine in patients with IBD and an approach to further determining its role in this patient population is discussed.

Topics: Adult; Animals; Azathioprine; Budesonide; Crohn Disease; Glucocorticoids; Herpes Zoster; Herpes Zoster Vaccine; Humans; Immunosuppressive Agents; Male; Perianal Glands

Topics: Aged; Budesonide; Colitis, Collagenous; Colon; Colonoscopy; Crohn Disease; Humans; Male; Mesalamine; Recurrence

Esophageal Crohn's disease (CD) is challenging and often a disabling phenotype of disease. We aimed to report the clinical, endoscopic, histologic features, and treatment outcomes of esophageal patients with CD.. Esophageal patients with CD evaluated at the Mayo Clinic in Rochester, MN, between January, 1998, and December, 2012, were identified.. Twenty-four cases of esophageal CD were identified. The median age of diagnosis was 23 years (range, 12-60). Twenty-one patients (88%) had extraesophageal CD and 8 patients (33%) had oral ulcers at the time of esophageal CD symptom onset. The majority of patients had esophageal-specific symptoms. Mid (29%) or distal (29%) esophagus was the most common site of involvement. Inflammatory esophageal CD (75%) was marked by superficial ulcerations (58%), erythema and/or erosions (50%), deep ulcerations (13%), and pseudopolyps (4%) on endoscopy. Four patients (17%) were found to have esophageal strictures and 2 patients (8%) had fistulizing disease. Chronic inflammation (83%) was seen on biopsy in the majority of cases with 5 patients having associated granulomas. In our series, inflammatory esophageal CD responded to prednisone, topical budesonide, or biologics. Stricturing esophageal CD was successfully treated with a combination of biologic therapy, immunomodulators, and serial dilations with/without steroid injections. Aggressive medical therapy with biologics and endoscopic therapy was used for fistulizing esophageal CD, however, was not universally effective.. Esophageal CD should be considered in all patients with CD with upper gastrointestinal symptoms. Early recognition, diagnosis, and aggressive medical and/or endoscopic treatment are needed for successful outcomes.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Biological Products; Budesonide; Child; Combined Modality Therapy; Crohn Disease; Dilatation; Drug Therapy, Combination; Esophageal Diseases; Esophagoscopy; Esophagus; Female; Humans; Immunologic Factors; Male; Middle Aged; Prednisone; Treatment Outcome; Young Adult

Topics: Anti-Inflammatory Agents; Beclomethasone; Bone and Bones; Budesonide; Calcium Compounds; Colitis, Ulcerative; Crohn Disease; Glucocorticoids; Humans; Inflammatory Bowel Diseases; Primary Health Care; Spain; Vitamin D; Vitamins

Iatrogenic adrenal insufficiency is a potential harmful side effect of treatment with corticosteroids. It manifests itself when an insufficient cortisol response to biological stress leads to an Addisonian crisis: a life-threatening situation. We describe a case of a patient who developed an Addisonian crisis after inappropriate discontinuation of budesonide (a topical steroid used in Crohn's disease) treatment. Iatrogenic adrenal insufficiency due to budesonide use has been rarely reported. Prescribers should be aware of the resulting risk for an Addisonian crisis.

Topics: Adrenal Insufficiency; Budesonide; Crohn Disease; Glucocorticoids; Humans; Iatrogenic Disease; Male; Middle Aged; Withholding Treatment

The link between Mycobacterium avium subsp. paratuberculosis (MAP) and Crohn's disease (CD) is supported by several studies that have reported the detection and isolation of MAP from human tissues, but causation has not yet been proven. Preliminary studies have shown higher levels of antibodies in sera from CD patients against secreted protein from MAP within human macrophages when compared to healthy controls. The immunogenicity of this protein in CD patients under different treatment regimes was evaluated.. Sera of 110 CD patients, 82 ulcerative colitis (UC), and 150 healthy controls were collected and the presence of antibodies against the mycobacterial protein tyrosine phosphatase PtpA was assayed using ELISA.. A statistically significant difference in the level of antibodies against PtpA was measured in untreated CD patients versus healthy controls, but variation in the antibody levels was observed when patients were subjected to different treatment regimens. UC patients showed no differences in the levels of antibodies against PtpA when compared to healthy controls.. CD patients under different drug treatments show a clear difference in the levels of antibodies against a protein secreted by MAP, suggesting that if MAP is active in the progress of CD, some treatments can be detrimental to its survival.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Bacterial; Antibodies, Monoclonal; Azathioprine; Bacterial Proteins; Budesonide; Case-Control Studies; Colitis, Ulcerative; Crohn Disease; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Infliximab; Male; Mesalamine; Middle Aged; Mycobacterium avium subsp. paratuberculosis; Prednisone; Protein Tyrosine Phosphatases; Young Adult

Topics: Anti-Inflammatory Agents; Azathioprine; Biopsy; Budesonide; Colonoscopy; Crohn Disease; Cystic Fibrosis; Drug Therapy, Combination; Female; Gastrointestinal Agents; Humans; Skin Diseases; Time Factors; Treatment Outcome; Young Adult

Topics: Budesonide; Clinical Trials as Topic; Colitis, Ulcerative; Crohn Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Humans; Intestinal Mucosa; Mesalamine; Phosphatidylcholines

Topics: Administration, Oral; Aged; Amyloidosis; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Humans; Male; Remission Induction

The use of the highly effective thiopurines as early therapeutic option in Crohn's Disease (CD) may be discouraged by the long time interval required to obtain clinical efficacy as also by their potential side effects. The development of non-invasive markers of responsiveness to thiopurines represents a major attempt in the clinical management of CD patients. Azathioprine is able to induce apoptosis of T cells. We studied the effect of thiopurines on "in vitro" T cell apoptosis, IFN-γ and IL-10 production in a group of CD patients with known response to a previous treatment with AZA.. Heparinized blood samples were drawn from 25 CD patients showing or not a previous responsiveness to a conventional azathioprine treatment (n=17 and n=8, respectively). CD4+ T cells were stimulated "in vitro" with aCD3/28 mAbs in the presence or absence of azathioprine, 6-mercaptopurine or 6-thioguanine. Apoptosis was assessed using Annexin V staining, and IFN-γ and IL-10 production in cell culture supernatants was evaluated by ELISA.. Apoptosis stimulation index (% of apoptotic cells in the presence of thiopurine/% of apoptotic cells in the absence of thiopurine) and IFN-γ stimulation index (IFN-γ production in the presence of thiopurine/IFN-γ production in the absence of thiopurine) were, respectively, significantly lower and higher in non-responder when compared to responder patients. No variation was observed in IL-10 production.. Evaluation of apoptosis and IFN-γ stimulation index of peripheral CD4+ T cell may be useful for a proper selection of CD patients candidate to thiopurine treatment.

Topics: Adalimumab; Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Apoptosis; Azathioprine; Budesonide; Cells, Cultured; Crohn Disease; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Infliximab; Interferon-gamma; Interleukin-10; Male; Mesalamine; Middle Aged; Retrospective Studies; T-Lymphocytes; Tumor Necrosis Factor-alpha; Young Adult

Budesonide (BUD) is being used in pediatric Crohn disease (CD) because it is believed to have the potential to reduce corticosteroid-related toxicity; however, few data are available describing its use. The aim of the present study was to describe BUD use in an inception cohort of pediatric patients with CD.. Data were derived from the prospective Pediatric IBD Collaborative Research Group Registry established in 2002 in North America. Use of BUD in children with CD was examined.. BUD was used in 119 of 932 (13%) of children with newly diagnosed CD, with 56 of 119 (47%) starting BUD ≤ 30 days of diagnosis (26/56 with ileum and/or ascending colon [IAC] disease). BUD was used as monotherapy (9%), in combination with 5-aminosalicylates (77%), or in combination with immunomodulators (43%). Forty-three percent (24/56) went on to receive conventional corticosteroid at some point following their first BUD course. For the 63 of 119 (53%) who started BUD beyond the diagnosis period, 51 of 63 (81%) also received prednisone, with BUD used as a means of weaning from prednisone in 17 of 63 (27%). Patients with IAC disease who received BUD ≤ 30 days of diagnosis were just as likely to have received conventional corticosteroids by 1 year as were those who did not receive BUD ≤ 30 days of diagnosis. Two-thirds (77/119) of patients received BUD for ≤ 6 months.. BUD is being used among pediatric patients newly diagnosed as having CD, although the majority does not have disease limited to the IAC. BUD monotherapy was rare, and further data are required to better define the role of BUD in the treatment of pediatric CD.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Anti-Inflammatory Agents; Budesonide; Child; Colon; Colonic Diseases; Crohn Disease; Drug Therapy, Combination; Female; Humans; Ileal Diseases; Ileum; Immunologic Factors; Male; Mesalamine; Prednisone; Young Adult

Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) with uncertain etiopathogenesis. CD can involve any site of gastrointestinal tract from the mouth to anus and is associated with serious complications such as bowel strictures, perforations, and fistula formation. The incidence and prevalence rates of CD in Korea are still lower than those of Western countries, but have been rapidly increasing during the past decades. Although there are no definitive curative modalities for CD, various medical and surgical therapies are currently applied for diverse clinical situations of CD. However, a lot of decisions on the management of CD are made depending on the personal experiences and choices of physicians. To suggest preferable approaches to diverse problems of CD and to minimize the variations according to physicians, guidelines for the management of CD are needed. Therefore, IBD Study Group of the Korean Association for the Study of the Intestinal Diseases has set out to develop the guidelines for the management of CD in Korea. These guidelines were developed using the adaptation methods and encompass the treatment of inflammatory disease, stricturing disease, and penetrating disease. The guidelines also cover the indication of surgery, prevention of recurrence after surgery, and CD in pregnancy and lactation. These are the first Korean guidelines for the management of CD and the update with further scientific data and evidences is needed.

Topics: Anti-Inflammatory Agents; Antibodies, Monoclonal; Antimetabolites, Antineoplastic; Budesonide; Crohn Disease; Databases, Factual; Female; Fistula; Humans; Infliximab; Intestinal Perforation; Male; Mercaptopurine; Mesalamine; Methotrexate; Prednisolone; Pregnancy; Recurrence; Risk Factors; Severity of Illness Index; Sulfasalazine

Topics: Abdomen; Adult; Anti-Inflammatory Agents; Budesonide; Choristoma; Crohn Disease; Humans; Magnetic Resonance Imaging; Male; Spleen; Tomography, X-Ray Computed

In inflammatory bowel diseases (IBD), matrix metalloproteinases (MMPs) participate in intestinal tissue damage and regenerative processes. MMP activity is inhibited by tissue inhibitors of MMPs (TIMPs) and plasma inhibitor, α₂-macroglobulin (α2M). We evaluated serum MMPs, their inhibitors and markers of neutrophil activity, myeloperoxidase (MPO) and human neutrophil elastase (HNE), during glucocorticoid (GC) and anti-TNF-α therapies in pediatric IBD, in aim to find new tools for assessment of therapeutic response.. Serum samples were collected before and within a month after the start of therapy with oral GC (n = 19) or anti-TNF-α agent (n = 16), and from 32 pediatric control patients. Serum levels of MMP-7, MMP-9, TIMP-1, TIMP-2, α2M, MPO, and HNE were analyzed with enzyme-linked immunoabsorbent assays (ELISA) and MMP-8 by immunofluorometric assay (IFMA). Disease activity was monitored with erythrocyte sedimentation rate (ESR), CRP, fecal calprotectin (FC), and physician's global assessment of clinical disease activity (PGA).. In IBD, pretreatment serum MMP-7, MMP-8, MMP-9, α2M, MPO, and HNE were elevated compared with controls. During GC therapy, MMP-7, TIMP-1, and MMP-7/TIMP-2 decreased (all p < 0.05). During anti-TNF-α therapy, MMP-7 decreased (p = 0.063), but remained higher than that after GC therapy (p < 0.05). α2M (p < 0.05) and HNE (p < 0.05) increased, the former higher than that in GC-treated patients. The levels of MMPs and their inhibitors did not markedly associate with inflammatory markers in blood or feces.. In pediatric IBD, serum MMP-7 mirrors disease activity, and together with TIMP-1, reflects GC therapy response. α₂-Macroglobulin expression parallels the anti-TNF-α response.

Topics: Adolescent; alpha-Macroglobulins; Anti-Inflammatory Agents; Antibodies, Monoclonal; Blood Sedimentation; Budesonide; C-Reactive Protein; Child; Child, Preschool; Colitis, Ulcerative; Crohn Disease; Feces; Female; Glucocorticoids; Humans; Infliximab; Leukocyte Elastase; Leukocyte L1 Antigen Complex; Male; Matrix Metalloproteinase 7; Matrix Metalloproteinase 8; Matrix Metalloproteinase 9; Peroxidase; Prednisolone; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2; Tumor Necrosis Factor-alpha

The aim of this study was to develop a shortened Crohn's Disease Activity Index (CDAI).. A short CDAI was developed retrospectively using patient-level data from four budesonide clinical trials to select variables from the full CDAI which best predicted health-related quality of life as measured by the Inflammatory Bowel Disease Questionnaire (IBDQ), using the multiple linear regression model. The validity, reliability, and responsiveness of the short CDAI compared to the original CDAI were determined using data from nine clinical trials of budesonide.. The variables selected for the short CDAI were abdominal pain, diarrhea frequency, and general well-being. In all nine studies involving 1373 patients with active and inactive CD (5863 visits), the Pearson correlation coefficients between the short CDAI scores and the original CDAI scores at baseline (r = 0.899, P < 0.001), and the score differences (r = 0.963, P < 0.001) were excellent. The short CDAI accounted for 82.4% of the variance of the original CDAI. The intraclass correlation coefficient for the short CDAI was marginally better than that for the full CDAI, and both demonstrated good reliability (r = 0.600 versus r = 0.549). In patients with active CD who remitted during follow-up, the mean short CDAI scores decreased from 247 to 97, a score difference of 150 ± 60 points (P < 0.001). In patients with stable CD who relapsed, the mean short CDAI scores increased from 109 to 244 points, a score difference of 135 ± 62 points (P < 0.001).. The short CDAI is a valid, reliable, and responsive tool for the measurement of CD activity.

Topics: Anti-Inflammatory Agents; Budesonide; Cohort Studies; Crohn Disease; Humans; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Reproducibility of Results; Retrospective Studies; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome

Topics: Adrenal Insufficiency; Aged; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Humans; Male

The introduction of immunosuppressants and biologic agents has led to active debate and research about optimal therapeutic strategies considering risk factors and predictors of clinical outcome in inflammatory bowel disease (IBD). Data about gender-specific treatment differences and risk factors is lacking for IBD. The aim of the present study was to evaluate gender-related differences in the treatment of a distinct IBD patient population treated in the Rhein-Main region, Germany.. Data about past medical history, disease status and medical treatment of 986 outpatients treated in ten gastroenterological practices and three hospitals were collected from November 1st 2005-July 31st 2007 and analyzed with regard to gender-related differences in therapy and disease management.. With the exception of an extended disease duration in women, no significant gender-related differences in demographic and clinical characteristics were observed. Men showed a significantly higher remission rate than women (p=0.025), while women received significantly less immunosuppressive medication compared to men (p=0.011). In addition, treatment with immunosuppressants was not different in women with child-bearing potential compared to menopausal women.. Our investigation demonstrates for the first time gender-specific differences in the therapeutic management in a large cohort of IBD patients.

Topics: Adrenal Cortex Hormones; Adult; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Azathioprine; Budesonide; Colitis, Ulcerative; Crohn Disease; Cross-Sectional Studies; Cyclosporine; Female; Germany; Humans; Immunosuppressive Agents; Infliximab; Male; Mercaptopurine; Mesalamine; Methotrexate; Middle Aged; Practice Patterns, Physicians'; Prospective Studies; Remission Induction; Severity of Illness Index; Sex Factors; Tacrolimus

Autoimmune disorders (AID) have been shown to be associated with chronic antibiotic-refractory pouchitis (CARP). The role of anti-microsomal antibodies in ileal pouch disorders has not been investigated. The aims of the study were to investigate the prevalence of positive anti-microsomal antibody in symptomatic patients with ileal pouches and to investigate its clinical implications.. A total of 118 consecutive symptomatic patients with ileal pouches were included between January and October 2010. Anti-microsomal antibodies were measured at the time of presentation. Demographic, clinical, and laboratory characteristics were compared between patients with positive and negative anti-microsomal antibody.. There were 14 patients (11.9%) with positive serum anti-microsomal antibody. The mean age of patients in the antibody positive and negative groups were 41.8 ± 14.4 and 42.0 ± 14.0 years, respectively (p = 0.189). All 14 patients in the antibody positive group (100%) had some form of AID, as compared to 20 patients (19.2%) in the antibody negative group (p < 0.001). Four (28.6%) patients in the antibody positive group had at least one AID in addition to Hashimoto's thyroiditis in contrast to four (3.8%) in the antibody negative group (p = 0.003). In addition, five (35.7%) patients had associated primary sclerosing cholangitis (PSC) in the antibody positive group compared to nine (8.7%) in the antibody negative group (p = 0.012). Eleven patients (78.6%) in the antibody positive group required steroids for treatment of pouch related symptoms in contrast to 26/104 (25%) patients in the antibody negative group (p = 0.002).. Anti-microsomal antibodies were common in pouch patients presenting with symptoms. Patients with positive anti-microsomal antibodies were much more likely to have concurrent AID and PSC. These patients were more likely to require therapy with steroids.

Topics: Adult; Anti-Bacterial Agents; Anti-Inflammatory Agents; Autoantibodies; Autoimmune Diseases; Budesonide; Cholangitis, Sclerosing; Crohn Disease; Drug Resistance, Bacterial; Female; Hashimoto Disease; Humans; Male; Middle Aged; Pouchitis

Topics: Adolescent; Biopsy, Needle; Budesonide; Crohn Disease; Diagnosis, Differential; Edema; Follow-Up Studies; Genital Diseases, Male; Granuloma; Humans; Immunohistochemistry; Lymphangitis; Male; Penile Diseases; Risk Assessment; Scrotum; Severity of Illness Index

Corticosteroids (CS) effectively induce remission in patients with moderate to severe Crohn's disease (CD). However, CS dependence in children is a significant clinical problem associated with numerous side effects. Identification of molecular markers of CS dependence is of paramount importance. The ABCB1 gene codes for P-glycoprotein, a transporter involved in the metabolism of CS. We examined whether DNA variation in the ABCB1 gene was associated with CS dependency in children with CD.. A retrospective study was carried out in two Canadian tertiary pediatric gastroenterology centers. Clinical information was abstracted from medical charts of CD patients (N = 260) diagnosed with CD prior to age 18 and administered a first course of CS during the 1 year since diagnosis. Patients were classified as CS-dependent if they relapsed during drug tapering or after the end of therapy. DNA was extracted from blood or saliva. Thirteen tagging single nucleotide polymorphisms (tag-SNPs) and a synonymous variation (C3435T) in the ABCB1 gene were genotyped. Allelic, genotype, and haplotype associations were examined using logistic regression and Haploview.. Tag-SNP rs2032583 was statistically significantly associated with CS dependency. The rare C allele of this SNP (odds ratio [OR] = 0.56, 95% confidence interval [CI]: 0.34-0.95, P = 0.029) and heterozygous genotype TC (OR = 0.52, 95% CI: 0.28-0.95, P = 0.035) conferred protection from CS dependency. A three-marker haplotype was significantly associated with CS dependence (multiple comparison corrected P-value = 0.004).. Our results suggest that the ABCB1 gene may be associated with CS dependence in pediatric CD patients.

Topics: Adolescent; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Budesonide; Child; Cohort Studies; Crohn Disease; DNA; Female; Genetic Predisposition to Disease; Genotype; Glucocorticoids; Haplotypes; Humans; Male; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Prednisone; Prognosis; Retrospective Studies

Outcomes of medical treatment in patients with stricturing and penetrating Crohn's disease (CD) are not well characterized.. Adults with stricturing and penetrating CD who underwent medical treatment from 2004 to 2008 were evaluated. We assessed response rates to medical treatment, time to relapse or surgery, and postoperative complications.. In all, 53 patients underwent medical therapy. 60% had stricturing disease, 11% had penetrating, and 28% had both. Disease location was ileal in 38%, colonic in 2%, and ileocolonic in 60%. At 30, 60, and 90 days, 54%, 60%, and 64% experienced a response to medical therapy, respectively. At 30 days, 75% of patients with ileal CD responded to therapy compared to 38% of patients with ileocolonic CD (P = 0.026). Overall, 64% of patients required surgery. Patients with ileocolonic disease required surgery at 0.55 years versus 1.07 years in patients with ileal disease (P = 0.023). 24% of patients experienced an anastomotic leak, fistula, or abscess (IASC). 29% of patients with penetrating disease developed IASC compared to 6% of patients with stricturing disease (P = 0.047). 32% of patients on biologic therapy had IASC compared to 0% of those not on biologics (P = 0.059).. The outcomes of medical treatment of stricturing or penetrating CD are poor, as 64% ultimately require surgery. Important factors that seem to be associated with either failed therapy include ileocolonic or colonic disease location. We report a high rate of IASC, especially in patients with penetrating disease and those treated with biologic therapy. This should be considered prior to attempted medical therapy.

Topics: Adult; Anti-Bacterial Agents; Budesonide; Cohort Studies; Constriction, Pathologic; Crohn Disease; Female; Glucocorticoids; Humans; Immunologic Factors; Male; Phenotype; Postoperative Complications; Prednisone; Retrospective Studies; Treatment Outcome

Topics: Abdominal Pain; Adult; Appendicitis; Budesonide; Colonoscopy; Crohn Disease; Diagnosis, Differential; Female; Glucocorticoids; Humans

Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Azathioprine; Budesonide; Clinical Trials as Topic; Colitis, Ulcerative; Crohn Disease; Drug Therapy, Combination; Gastrointestinal Agents; Glucocorticoids; Humans; Immunosuppressive Agents; Infliximab; Mesalamine; Methotrexate; Practice Guidelines as Topic; Prednisolone; Remission Induction

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Budesonide; Chromosomes, Human, Pair 7; Combined Modality Therapy; Crohn Disease; Cytarabine; Drug Therapy, Combination; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Humans; Idarubicin; Immunosuppressive Agents; Leukemia, Monocytic, Acute; Male; Mercaptopurine; Mesalamine; Methyltransferases; Monosomy; Myelodysplastic Syndromes; Prednisone; Young Adult

Budesonide exhibits similar efficacy to systemic glucocorticosteroids (GCSs) in Crohn's disease (CD), but with fewer adverse events (AEs). Aim To evaluate budesonide's safety profile in CD patients, in particular, incidences of clinically important AEs known to be associated with systemic GCSs.. Five 1-year, double-blind, placebo-controlled trials evaluating budesonide for mild-to-moderate CD were pooled for analysis.. The highest incidence rates of AEs were gastrointestinal- and endocrine systems-related in both groups (budesonide 6 mg/day, n = 208; placebo, n = 209). Incidence rates were similar, except for higher incidence of endocrine disorders in budesonide versus placebo patients (P = 0.0042) caused by a higher overall occurrence of cutaneous GCS symptoms (P = 0.0036) in the budesonide group; differences in individual symptoms were nonsignificant. Percentage of patients with normal adrenal function was significantly lower at 13 weeks (three of five studies), but not at 52 weeks (two studies) in the budesonide versus placebo groups. Occurrence of clinically important or serious AEs associated with systemic GCSs, including sepsis, cataracts, adrenal insufficiency was rare and similar between groups.. Budesonide treatment for up to 1 year is well-tolerated in CD patients, with an AE profile similar to placebo and only rare occurrences of clinically important AEs associated with systemic GCSs.

Topics: Anti-Inflammatory Agents; Budesonide; Crohn Disease; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Randomized Controlled Trials as Topic; Remission Induction; Secondary Prevention; Treatment Outcome

A 39-year-old white woman with longstanding Crohn's disease presented with the rare complication of granulomatous bronchiolitis. Rapid resolution after inhaled budesonide is highlighted, as this is the first case described in the literature successfully treated without the need for systemic therapy. This less toxic approach to therapy is warranted in granulomatous bronchiolitis of Crohn's disease to avoid unwanted side effects of steroids and infliximab.

Topics: Adult; Anti-Inflammatory Agents; Bronchiolitis; Bronchodilator Agents; Budesonide; Crohn Disease; Female; Glucocorticoids; Granuloma, Respiratory Tract; Humans; Tomography, X-Ray Computed

We sought to determine whether treatment with steroids, immunosuppressives (ISs), and anti-tumor necrosis factor (TNF) agents is associated with an increased risk of adverse events in patients with Crohn's disease (CD).. This study analyzed claims from patients with CD and controls without CD from the United States with private insurance (2002-2005). Patients were classified by treatment with steroids, ISs, anti-TNF agents, combinations of two or three, and none of these medications. Follow-up adverse events in patients with CD and controls were compared across different treatment categories and are presented as hazard ratios (HRs) and 95% confidence intervals (CIs). Within the CD patients, a subset analysis examined the relationship between therapies and outcomes.. A total of 22,310 patients with CD (8,581 longitudinal cohort cases) and 111,550 controls were identified. Compared with the controls, CD patients had higher rate ratios for all pre-specified events. Within the CD patient population subgroup, monotherapy with steroids, ISs, or anti-TNF agents was associated with an increased risk of tuberculosis (TB) (HR 2.7; 95% CI, 1.0-7.3), candidiasis (HR 2.7; 95% CI, 1.8-4.0), herpes zoster (HR 1.7; 95% CI, 1.0-2.7), sepsis (HR 1.3; 95% CI, 1.1-1.5), demyelinating conditions (HR 3.2; 95% CI, 1.5-6.9), and cervical dysplasia (HR 1.5; 95% CI, 1.2-2.0) as compared with patients not receiving these medications. The use of two or three of these medications further increased these risks: TB (HR 7.4; 95% CI, 2.1-26.3), candidiasis (HR 3.8; 95% CI, 2.0-7.6), herpes zoster (HR 3.7; 95% CI, 1.8-7.5), sepsis (HR 1.6; 95% CI, 1.2-2.1), and cervical dysplasia (HR 1.8; 95% CI, 1.1-3.0).. Treatment with steroids, ISs, or anti-TNF agents singly and in combination in patients with CD is associated with increased risks of infection, demyelinating disorders, and cervical dysplasia.

Topics: Adalimumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Azathioprine; Budesonide; Case-Control Studies; Comorbidity; Crohn Disease; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Infliximab; Longitudinal Studies; Male; Mercaptopurine; Methotrexate; Middle Aged; Outcome Assessment, Health Care; Prednisone; Prevalence; Proportional Hazards Models; Steroids; United States

Treatment decision making for postoperative Crohn's disease is complex because of the increasing number of maintenance therapies available with competing risk-benefit profiles. The main objective of this study was to determine the distribution of patients' preferences for selected postoperative maintenance therapies.. The study was a cross-sectional survey in which patients with Crohn's disease completed a standardized interview. Each participant completed 5 tasks that compared: (1) no medication and 5-ASA, (2) fish oil and 5-ASA, (3) metronidazole and 5-ASA, (4) budesonide and 5-ASA, and (5) azathioprine and 5-ASA. For each task, the minimum change in treatment effect size between the 2 treatments that the participant considered worthwhile was determined.. The distribution of the participants' preference scores varied widely for each task. When fish oil, metronidazole, budesonide, and azathioprine were considered equally effective to 5-ASA, 92.9%, 28.8%, 38.4%, and 19% of the participants, respectively, preferred these medications relative to 5-ASA. These percentages increased to 98.4%, 54.8%, 61.9%, and 50.8%, respectively, when fish oil, metronidazole, budesonide, and azathioprine were considered to offer a 5% absolute risk reduction relative to 5-ASA. Regression analysis did not identify any clinical or demographic variables predictive of the participants' treatment preferences.. The participants' preferences for postoperative maintenance therapies were widely distributed, and no clinical or demographic factors predicted these preferences. This emphasizes the need for effective communication between physician and patient in order to select the treatment options most consistent with a patient's informed preferences.

Topics: Adult; Aged; Azathioprine; Budesonide; Canada; Crohn Disease; Cross-Sectional Studies; Decision Support Techniques; Fees, Pharmaceutical; Female; Fish Oils; Focus Groups; Gastrointestinal Agents; Humans; Male; Mesalamine; Metronidazole; Middle Aged; Patient Satisfaction; Postoperative Care; Regression Analysis; Reproducibility of Results; Secondary Prevention

Topics: Acidosis; Budesonide; Crohn Disease; Feces; Female; Glucocorticoids; Humans; Hypokalemia; Intestinal Mucosa; Middle Aged; Potassium

Patients with Crohn's disease may experience several non-digestive complications, including muscle disorders. Rabdomyolysis has rarely been reported in patients with inflammatory bowel disease, however a number of factors may cause muscular damage in this setting. We report the case of a young woman with Crohn's disease who developed a severe, symptomatic skeletal muscle damage associated with severe hypokaliemia. Reversal of the potassium levels to normal ranges led to clinical resolution. The possible causes that might have lead to hypokalemia development and subsequent rhabdomyolysis are discussed with special emphasis for the potential causative role of medical treatment, especially budesonide for which similar side effects have been previously reported. Physicians should be aware that hypokalemia is possible in the setting of Crohn's disease and muscle damage can present as a complication.

Topics: Adult; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Female; Follow-Up Studies; Humans; Hypokalemia; Infusions, Intravenous; Potassium Chloride; Rhabdomyolysis

The neurological manifestations of Crohn's disease are rare, dominated by multiple mononeuropathies and the abnormalities of the white matter. Polyradiculoneurities remain exceptional.. We report the case of a 33-year-old patient admitted for an ascending weakness of all four limbs. Eight years earlier he had presented a similar episode which had regressed spontaneously. The neurological examination revealed a tetraparesis with areflexia and hypotonia. These manifestations were concomitant with chronic diarrhea which had been neglected to date. The electrophysiological aspect was compatible with an acute polyradiculoneuritis. The analysis of the cerebrospinal fluid showed an albumino-cytological dissociation. The existence of the diarrhea directed the investigations towards an inflammatory enteropathy, which was attested later on by the endoscopic, radiologic and histological data leading to the diagnosis of active Crohn's disease. The diagnosis of a relapsing polyradiculoneuritis associated with Crohn's disease was retained. The patient was treated by salazopyrine-budesonide with improvement in the digestive and neurological manifestations after 3 years.. The frequency of neurological features in Crohn's disease is not well documented. The incriminated mechanisms are either directly related to the disease (deficit in B12 vitamin or folic acid and/or by the means of an auto-immune vascularitis) or secondary to long-term treatment with metronidazole. The course of neurological manifestations is largely dependent on the course of the inflammatory disease.

Topics: Adult; Anti-Inflammatory Agents; Budesonide; Combined Modality Therapy; Crohn Disease; Diarrhea; Drug Combinations; Drug Therapy, Combination; Glucosamine; Humans; Malabsorption Syndromes; Male; Neural Conduction; Plasma Exchange; Polyradiculoneuropathy; Quadriplegia; Recurrence; Sulfasalazine

Topics: Administration, Oral; Adolescent; Adult; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Female; Humans; Long-Term Care; Male; Middle Aged; Remission Induction; Safety; Time Factors; Treatment Outcome

Topics: Adult; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Diagnosis, Differential; Drug Therapy, Combination; Female; Humans; Intestine, Small; Mesalamine; Pregnancy; Pregnancy Complications; Ultrasonography

Topics: Anti-Inflammatory Agents; Budesonide; Crohn Disease; Humans; Remission Induction; Secondary Prevention

Symptomatic respiratory tract involvement is not common in Crohn's disease. Upper-airway obstruction has been reported before in Crohn's disease and usually responds well to steroid treatment.. We report a case of a 32-year old patient with Crohn's disease who presented with progressively worsening dyspnea on exertion. Magnetic Resonance Imaging of the chest and bronchoscopy revealed severe tracheal stenosis and marked inflammation of tracheal mucosa. Histopathology of the lesion showed acute and chronic inflammation and extended ulceration of bronchial mucosa, without granulomas. Tracheal stenosis was attributed to Crohn's disease after exclusion of other possible causes and oral and inhaled steroids were administered. Despite steroid treatment, tracheal stenosis persisted and only mild symptomatic improvement was noted after 8 months of therapy. The patient subsequently underwent rigid bronchoscopy with successful dilatation and ablation of the stenosed areas and remission of her symptoms.. Respiratory involvement in Crohn's disease might be more common than appreciated. Interventional pulmonology techniques should be considered in cases of tracheal stenosis due to Crohn's disease refractory to steroid treatment.

Topics: Adult; Anti-Inflammatory Agents; Bronchoscopy; Budesonide; Crohn Disease; Dyspnea; Female; Humans; Magnetic Resonance Imaging; Methylprednisolone; Respiratory Mucosa; Trachea; Tracheal Stenosis

Topics: Anti-Inflammatory Agents; Budesonide; Crohn Disease; Dementia; Humans; Male; Middle Aged; Parkinson Disease, Secondary

In a previous, controlled study, it was shown that orally administered budesonide increases the absorptive capacity of the intestinal mucosa in patients with ileostomies caused by Crohn's disease. This open, nonrandomized study was designed to analyze this functional, not inflammation-dependent steroid-effect in the long-term course comparing exposure, withdrawal, and reexposure.. Phase 1: 23 patients without inflammatory activity of the disease received oral budesonide (3 mg t.i.d.) for at least four weeks (36.7 weeks; standard deviation, 45.3 weeks) because of high intestinal output syndrome. Phase 2: Medication was stopped for four weeks. Phase 3: Medication as in Phase 1. In each phase the weight of the ileostomy bags was measured with a spring balance before emptying and documented in a diary. Mean values per day and per week were calculated and the differences statistically evaluated by the Wilcoxon-(Pratt)-test.. Comparing the last week of Phase 1 to first week of Phase 2, a significant (P < 0.0001) increase of the intestinal output (295 g; standard deviation, 313 g) was observed after omitting budesonide. In contrast, comparing the last week of Phase 2 to Phase 3, a significant (P < 0.0001) decrease of the intestinal output by 323.7 g (standard deviation, 322.2 g) was noticed reaching the same level as in Phase 1.. These data show that the functional, inflammation-independent effect of budesonide on the intestinal mucosa is strongly correlated to the administration of the drug and may be maintained long-term. These results should be confirmed by a larger number of patients.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Female; Humans; Ileostomy; Male; Middle Aged; Statistics, Nonparametric; Syndrome; Treatment Outcome

Topics: Administration, Oral; Administration, Rectal; Adrenal Cortex Hormones; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Clinical Trials as Topic; Colitis, Ulcerative; Crohn Disease; Drug Therapy, Combination; Evidence-Based Medicine; Gastrointestinal Agents; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Mesalamine; Quality of Life; Sulfasalazine; Time Factors

This case report describes a rare situation in which a superinfected cyst of the urachus complicated initially unknown and inactive Crohn's disease.. A 21-year-old man presented a chronic fever finally attributed to a superinfected urachal cyst. Six months after ablation of the cyst, progressive Crohn's disease was diagnosed.. The association of Crohn's disease and a superinfected urachal cyst is extremely rare. The case reported here is original in two aspects: the slowly progressive Crohn's disease was diagnosed after its complication; the superinfection developed through local bacterial translocation (ileal loop adjacent to the urachal cyst).

Topics: Adult; Anti-Inflammatory Agents; Budesonide; Chronic Disease; Crohn Disease; Disease Progression; Fever; Humans; Male; Time Factors; Tomography, X-Ray Computed; Urachal Cyst

Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Crohn Disease; Humans; Immunosuppressive Agents; Mesalamine; Prednisolone; Secondary Prevention

Systemic corticosteroid therapy increases risk of postoperative sepsis in Crohn's disease. This study investigates its effect on risk for sepsis in non-operated patients.. A retrospective case-control study was performed in 432 patients with Crohn's disease (the 94% of our database for whom adequate documentation could be retrieved). Two analyses were performed. The first tested the hypothesis that patients with perforating Crohn's disease (n = 86) were more likely to develop intra-abdominal or pelvic abscess (n = 29) if they had received systemic corticosteroids during the previous 3 months. The second analysis, confined to interventions since 1998, tested the hypothesis that corticosteroid therapy was more common during the 3 months before presentation with intra-abdominal or pelvic abscess (n = 12) than during the 3 months after presentation with a relapse of nonperforating disease (n = 24 consecutive patients). In both analyses adjustment was made for any other significant variable.. Systemic corticosteroid therapy was associated with an adjusted odds ratio (OR) for intra-abdominal or pelvic abscess of 9.03 (95% confidence interval [CI], 2.40-33.98) in patients with perforating Crohn's disease. Patients receiving prednisolone > or = 20 mg per day had an OR of 2.81 (95% CI, 0.99-7.99) for abscess compared with those receiving a lower dose. In patients with relapsed active disease, corticosteroid therapy was associated with an unadjusted OR of 9.31 (95% CI, 1.03-83.91) for intra-abdominal or pelvic abscess. Neither smoking nor azathioprine usage was associated with increased risk for abscess.. Systemic corticosteroid therapy for Crohn's disease is associated with increased risk for intra-abdominal or pelvic abscess.

Topics: Abdominal Abscess; Administration, Oral; Adult; Anti-Inflammatory Agents; Budesonide; Confidence Intervals; Crohn Disease; Female; Follow-Up Studies; Humans; Incidence; Male; Odds Ratio; Pelvis; Prednisolone; Retrospective Studies; Risk Factors

Patients with Crohn's disease suffer from intestinal bile acid malabsorption. Intestinal bile acid absorption is mediated by the apical sodium dependent bile acid transporter ASBT/IBAT (SLC10A2). In rats, ASBT is induced by glucocorticoids.. To study whether human ASBT is activated by glucocorticoids and to elucidate the mechanism of regulation.. ASBT expression in ileal biopsies from patients with Crohn's disease and from healthy subjects was quantified by western blot. ASBT promoter function was studied in luciferase assays and by electrophoretic mobility shift assay.. In 16 patients with Crohn's disease, ASBT expression was reduced to 69 (7.5)% compared with healthy controls (mean (SEM); p = 0.01). In 10 healthy male volunteers, ASBT protein expression was increased 1.34 (0.11)-fold (mean (SEM); p<0.05) after 21 days' intake of budesonide (9 mg/day) whereas expression of the peptide transporter 1 was unaffected. Reporter constructs of the human ASBT promoter were activated 15-20-fold by coexpression of the glucocorticoid receptor (GR) and exposure to the GR ligands dexamethasone or budesonide. Two glucocorticoid response elements in the ASBT promoter, arranged as inverted hexanucleotide repeats (IR3 elements), conferred inducibility by GR and dexamethasone in a heterologous promoter context and were shown to bind GR in mobility shift assays.. Human ASBT is induced by glucocorticoids in vitro and in vivo. Induction of ASBT by glucocorticoids could be beneficial in patients with Crohn's disease who exhibit reduced ASBT expression. This study identifies ASBT as a novel target of glucocorticoid controlled gene regulation in the human intestine.

Topics: Adult; Anti-Inflammatory Agents; Bile Acids and Salts; Blotting, Western; Budesonide; Carrier Proteins; Cells, Cultured; Crohn Disease; Dexamethasone; Electrophoretic Mobility Shift Assay; Gastrointestinal Agents; Glucocorticoids; Humans; Ileum; Ligands; Male; Organic Anion Transporters, Sodium-Dependent; Promoter Regions, Genetic; Receptors, Glucocorticoid; Symporters; Transcriptional Activation

Topics: Algorithms; Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Azathioprine; Budesonide; Crohn Disease; Defensins; Humans; Immunosuppressive Agents; Mesalamine; Prednisolone; Prognosis; Time Factors; Trichuris

Steroid resistance is a major problem in the management of patients with inflammatory bowel disease. In Crohn disease, poor response to corticosteroids has been related to increased expression of the drug efflux pump, P-glycoprotein. However, it has not been investigated thoroughly whether corticosteroids commonly used for drug therapy in inflammatory bowel disease are substrates of P-glycoprotein. We tested the hypothesis that budesonide and prednisone are substrates of P-glycoprotein thereby possibly contributing to variable therapeutic effects. Polarized, basal to apical transport of [3H]budesonide and [3H]prednisone was studied in monolayers of L-MDR1 cells (LLC-PK1 cells stably transfected with human MDR1 cDNA) and Caco-2 cells, both of which express P-glycoprotein in their apical membrane. Drug transport was measured during 4 hours at substrate concentrations of 5 microM. Net transport rates and permeability coefficients were calculated. Inhibition of P-glycoprotein-mediated transport across Caco-2 monolayers was determined after addition of the P-glycoprotein inhibitor PSC-833. The net transport rate from the basolateral to the apical side was significantly higher in L-MDR1 than in LLC-PK1 cells for both budesonide and prednisone. Apparent permeability coefficients of budesonide and prednisone reflected polarized transport from basal to apical. PSC-833 inhibited the polarized transport of both corticosteroids. In conclusion, budesonide and prednisone were identified as substrates of the intestinal drug efflux pump, P-glycoprotein. Therefore, drug secretion via P-glyco-protein into gut lumen might play a more important role in pharmacokinetics and pharmacodynamics of these corticosteroids than currently appreciated in gastroenterological practice.

Topics: Anti-Inflammatory Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; Budesonide; Cell Culture Techniques; Colonic Neoplasms; Crohn Disease; Drug Resistance, Multiple; Humans; Permeability; Prednisone; Tumor Cells, Cultured

Studies have demonstrated that budesonide is effective in the treatment of active Crohn's disease. Due to its extensive hepatic metabolism, budesonide has much lower adverse events compared to prednisolone. Consequently, the low systemic availability restricts its application to Crohn's disease of the terminal ileum and the colon. Esophageal ulceration is a rare complication of Crohn's disease. This article describes the case of a young lady who presented at the age of 16 with active Crohn's disease of the terminal ileum and the colon without dysphagia or pain in the chest. Her disease was successfully treated with prednisolone for almost two years. Because of weight gain, acne, and moon face she was switched to budesonide. A few days later she presented with intractable pain of the esophagus, dysphagia, and inability to eat. Endoscopy demonstrated aphthous ulcerations of the esophagus and the histology was compatible with Crohn's disease. After two weeks of treatment with prednisolone all symptoms resolved and at follow-up gastroscopy ulcers had disappeared.

Topics: Adolescent; Budesonide; Crohn Disease; Esophagitis; Female; Humans; Peptic Ulcer; Prednisolone; Treatment Outcome

Systemic glucocorticosteroid therapy is effective in Crohn's disease, but is associated with side-effects. Budesonide has high topical anti-inflammatory activity, but considerably lower systemic activity than other oral glucocorticosteroids.. To evaluate the systemic exposure to budesonide (controlled ileal release capsules) in children and adults with active Crohn's disease, and to assess the suppression of plasma cortisol.. In an open label study, patients (eight children and six adults) with active Crohn's disease received 9 mg budesonide (Entocort capsules) orally once daily for 7 days. Plasma concentrations were determined on the seventh day of administration, and pharmacokinetic parameters were calculated. For reference, 0.5 mg budesonide was given intravenously separately. Plasma cortisol levels were compared with the pre-treatment baseline values.. Systemic exposure to budesonide (AUC0-24 h) after 1 week of oral administration was 41 +/- 21 nmol/L x h (mean +/- s.d.) in children and 35 +/- 20 nmol/L x h in adults. The estimated systemic availability in children was 9 +/- 5% and in adults 11 +/- 7%. The mean plasma cortisol (AUC0-24 h) decreased by 64 +/- 18% in children and by 50 +/- 27% in adults.. The systemic exposure, systemic availability and cortisol suppression after oral administration of 9 mg budesonide were similar in children and adults with active Crohn's disease. Budesonide was well tolerated and no clinically important safety-related findings were identified.

Topics: Administration, Oral; Adolescent; Adult; Anti-Inflammatory Agents; Budesonide; Capsules; Child; Crohn Disease; Delayed-Action Preparations; Female; Humans; Hydrocortisone; Infusions, Intravenous; Male

Topics: Acute Disease; Adult; Age Factors; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Azathioprine; Budesonide; Child; Controlled Clinical Trials as Topic; Crohn Disease; Drug Therapy, Combination; Follow-Up Studies; Humans; Immunosuppressive Agents; Mercaptopurine; Mesalamine; Meta-Analysis as Topic; Nutritional Physiological Phenomena; Prednisolone; Time Factors

Topics: Administration, Oral; Adult; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Azathioprine; Budesonide; Child; Crohn Disease; Enzyme Inhibitors; Female; Folic Acid Antagonists; Gastrointestinal Agents; Humans; Immunosuppressive Agents; Infliximab; Male; Mercaptopurine; Mesalamine; Meta-Analysis as Topic; Methotrexate; Placebos; Postoperative Care; Prednisolone; Pregnancy; Prognosis; Prospective Studies; Randomized Controlled Trials as Topic; Recurrence; Remission Induction; Risk Factors; Time Factors

Treatment options for patients with Crohn disease (CD) have expanded, but the use of some of these options in pediatric patients remains controversial. The authors evaluate current trends in treatment and areas of consensus or controversy.. An international survey of certified pediatric gastroenterologists was conducted using an e-mail questionnaire in an attempt to evaluate management of active Crohn disease, attitudes toward four types of therapy, and prevalence of testing for osteopenia and 6-thioguanine levels.. One hundred sixty-seven physicians from the United States, Canada, Western Europe, and Israel were included. The majority of North American physicians (71%) prefer to use conventional steroids and azathioprine (AZA) before nutritional therapy or budesonide for patients with mild to moderately active disease, versus 21% of Western Europeans (P < 0.001). Western Europeans prefer nutritional therapy followed by budesonide or steroids for those with mild or moderate disease. Only 4% of North American gastroenterologists use nutritional therapy frequently versus 62% of their Western European colleagues (P < 0.001). Infliximab was thought to be effective for steroid-unresponsive disease by almost all physicians surveyed, although its efficacy as a maintenance therapy was rated higher by North American physicians than by their Western European and Israeli colleagues (P < 0.01). Bone mineral density is routinely evaluated by about 45% of physicians in Western Europe and North America.. Attitudes toward current therapies vary significantly by region, with North Americans strongly favoring corticosteroids followed by immunomodulatory therapy, and Western Europeans favoring nutritional therapy or budesonide and the avoidance of conventional corticosteroids.

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Attitude of Health Personnel; Azathioprine; Bone Density; Budesonide; Consensus; Crohn Disease; Gastroenterology; Gastrointestinal Agents; Humans; Immunosuppressive Agents; Infliximab; Pediatrics; Practice Guidelines as Topic; Surveys and Questionnaires

Topics: Aminosalicylic Acids; Anti-Bacterial Agents; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Humans; Ileum; Nitroimidazoles; Recurrence; Smoking

Topics: Budesonide; Colitis, Ulcerative; Colon; Crohn Disease; Delayed-Action Preparations; Glucocorticoids; Humans; Ileum; Inflammatory Bowel Diseases

Patients with Crohn's disease (CD) have increased energy expenditure and fat oxidation. Steroids, commonly used to treat flare-up of CD, induce weight gain. This study was designed to evaluate the effects of prednisone and budesonide on energy expenditure and substrate oxidation in patients with CD.. Twenty-nine women with CD and 10 healthy controls were studied. Ten patients received prednisone (0.75-1.0 mg/kg/day), nine received budesonide (9 mg/ day), and 10 did not receive steroids. Resting energy expenditure and substrate oxidation were measured by indirect calorimetry in a fasting state and after a standard diet.. In the fasting state, resting energy expenditure was higher in patients without steroids than in the controls. Lipid oxidation was lower (p < 0.01) in patients with prednisone (0.46 +/- 0.39 mg/kg/min) than in patients with budesonide (0.97 +/- 0.28 mg/kg/min) and without steroids (1.06 +/- 0.32 mg/kg/min), but was similar with control subjects (0.47 +/- 0.20 mg/kg/min). Postprandially, lipid oxidation was lower (p < 0.01) in patients with prednisone (0.32 +/- 0.23 mg/kg/min) than in patients with budesonide (0.75 +/- 0.20 mg/kg/min), without steroids (0.82 +/- 0.23 mg/kg/min), and controls (0.58 +/- 0.15 mg/kg/min). Protein oxidation was significantly higher in patients with prednisone than in the other subjects.. In women with CD, prednisone decreases lipid oxidation and increases protein oxidation. These effects are not observed with budesonide and may contribute to the weight gain and side effects commonly observed with prednisone. A low-fat/high-protein diet could be proposed during a course of prednisone.

Topics: Adult; Anti-Inflammatory Agents; Body Composition; Budesonide; Calorimetry, Indirect; Case-Control Studies; Crohn Disease; Drug Administration Schedule; Energy Metabolism; Female; Humans; Lipid Peroxidation; Middle Aged; Prednisone; Proteins; Substrate Cycling

Oral budesonide has been found to be efficacious for mild to moderate Crohn's disease in adults, with equal improvement rates for budesonide and prednisone. We report the results of a retrospective study of budesonide treatment in mild to moderate Crohn's disease in children.. Charts of patients treated with budesonide (n = 62) with a pediatric Crohn's Disease Activity Index of 12.5 to 40 were compared with a cohort of 58 age-matched patients treated with prednisone.. Among children treated with budesonide, 48% had remission compared with 77% of the children treated with prednisone (P =.001). Among patients who had failed previous medical therapy with mesalamine, 59% had remission with budesonide (9 mg/day). Remission with prednisone occurred in 73% of children who failed to achieve remission with budesonide. Patients responding to budesonide had significantly milder disease compared with nonresponders who had remission while taking prednisone.. Budesonide is useful in mild to moderate Crohn's disease in children. It is more effective than mesalamine and antibiotics but less effective than prednisone. Budesonide should be considered for first-line therapy in mild to moderate Crohn's disease.

Topics: Administration, Oral; Administration, Topical; Adolescent; Anti-Inflammatory Agents; Budesonide; Child; Crohn Disease; Female; Glucocorticoids; Growth; Humans; Male; Prednisone; Recurrence; Retrospective Studies; Severity of Illness Index

Topics: Budesonide; Crohn Disease; Dose-Response Relationship, Drug; Drug Interactions; Randomized Controlled Trials as Topic

To create a concept for measuring and valuating resource utilization of outpatient treatment of patients with inflammatory bowel disease in a German university hospital.. The measurement of health services was achieved using a computer-based routinely administered data base of the Medical Department. Measuring costs was performed in three steps: 1. identification of the categories of resource utilization, 2. quantitative measurement of resource use, 3. monetary valuation of the utilization of resources using German fee schedules and prices for drugs.. The resource utilization of 272 patients with a treatment period of more than 1 year could be identified in a structured form. Categories of resource use could be identified and quantitatively measured as follows: anamnesis and physical examination by a physician in 100% of the visits, laboratory tests in 87.1%, endoscopic or sonographic services in 36.9%, and radiologic procedures in 14.1%. In 93.6% of the visits a medication was prescribed. Annual costs of outpatient care provided by the hospital were 3,171 [symbol: see text] per patient. Medication accounted for 85% of total costs. Analyzing the costs of medical treatment, mesalazine was the major cost component (48%), followed by budesonide (15%).. The presented concept offers a good access to measure costs of outpatient treatment of patients with inflammatory bowel disease. It is suitable for measuring costs in the economic evaluation of alternative treatments or diagnostic strategies in an outpatient setting. It furthermore may be used as a component in cost-of-illness studies. For transferring the concept to other hospitals, the availability of a routine documentation of services should be checked. For economic analysis, a further data management is required.

Topics: Adult; Ambulatory Care; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Colitis, Ulcerative; Cost of Illness; Costs and Cost Analysis; Crohn Disease; Drug Costs; Germany; Health Care Costs; Health Resources; Hospitals, University; Humans; Mesalamine

Topics: Anti-Inflammatory Agents; Bone Density; Budesonide; Crohn Disease; Humans

Corticosteroids may contribute to the bone loss associated with Crohn's disease (CD). We investigated the effect on bone mineral density (BMD) of treatment with budesonide, a steroid with low systemic activity, and compared the outcome with prednisone and nonsteroid therapy in patients with CD.. Prospective annual BMDs of the lumbar spine (LS) and femoral neck (FN) were measured for 2 yr in 138 patients with quiescent CD treated with mean daily doses of 8.5 mg of budesonide (n = 48), 10.5 mg of prednisone (n = 45), or nonsteroid drugs (n = 45).. Between baseline and 1 yr, the mean LS BMD decreased 2.36% in the budesonide group (p < 0.001), 0.61% in the prednisone group (ns), and 0.09% in the nonsteroid group (ns). The difference between budesonide and nonsteroid groups was significant (p = 0.003). In the 2nd yr, LS BMD did not change in the three groups. After 2 yr, FN BMD decreased 2.94% in the budesonide group (p < 0.01), 0.36% in the prednisone group (ns), and 1.05% in the nonsteroid group (ns); the differences among groups were not significant. The proportion of patients with bone loss of >2% per annum at the LS and FN was higher in the budesonide group than in the nonsteroid group (p < 0.001) and prednisone group (p < 0.05).. Patients with CD receiving maintenance treatment for 2 yr with prednisone show little change in BMD, whereas treatment with budesonide may be associated with LS and FN bone loss. Budesonide does not confer an advantage over low-dose prednisone for the preservation of BMD.

Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Bone Density; Budesonide; Crohn Disease; Female; Femur Neck; Humans; Longitudinal Studies; Lumbar Vertebrae; Male; Middle Aged; Prednisone; Prospective Studies; Time Factors; Treatment Outcome

Topics: Adult; Aerosols; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Gingivitis; Humans; Male; Oral Hygiene

Topics: Azathioprine; Budesonide; Crohn Disease; Glucocorticoids; Humans; Ileum; Mesalamine; Prednisolone

Topics: Administration, Topical; Anti-Inflammatory Agents; Biological Availability; Budesonide; Crohn Disease; Delayed-Action Preparations; Drug Administration Schedule; Humans; Randomized Controlled Trials as Topic

Topics: Anti-Inflammatory Agents; Budesonide; Crohn Disease; Humans; Randomized Controlled Trials as Topic; Research Design; Sample Size; Therapeutic Equivalency; Treatment Outcome

Oral budesonide in adult studies is a potent corticosteroid with decreased systemic bioavailability and an improved adverse effect profile in comparison with prednisone. It has recently been introduced for the treatment of inflammatory bowel disease in Europe, Canada, and Israel. Benign intracranial hypertension has rarely been associated with corticosteroid therapy but has not been reported in association with budesonide therapy. Three adolescents with Crohn's disease and poor nutritional status developed benign intracranial hypertension while receiving oral budesonide. All three patients had previously received multiple courses of prednisone during the course of their disease, without developing intracranial hypertension. Benign intracranial hypertension resolved after medication withdrawal and did not recur with subsequent use of prednisone. Evaluation for benign intracranial hypertension should be considered in patients with inflammatory bowel disease who develop headache while receiving oral budesonide. This side effect may be associated with poor nutritional status.

Topics: Adolescent; Budesonide; Crohn Disease; Female; Humans; Male; Nutritional Status; Prednisone; Pseudotumor Cerebri; Risk Factors

Topics: Adult; Budesonide; Crohn Disease; Female; Glucocorticoids; Humans; Ileitis; Mood Disorders; Prednisone

Topics: Budesonide; Crohn Disease; Follow-Up Studies; Humans; Treatment Outcome

Although the effectiveness of controlled ileal release (CIR) budesonide in children can be extrapolated from adult studies, there are currently no data available concerning the effects of CIR budesonide therapy on linear growth. In the absence of controlled, prospective pediatric clinical trials, we reviewed the outcomes, particularly linear growth, of children and adolescents given CIR budesonide to treat active intestinal inflammation and to maintain remission.. Thirty-two children (20 males) aged 14.1 +/- 2.7 years with Crohn disease of the distal ileum with or without right colon involvement were treated for active Crohn disease (baseline Pediatric Crohn Disease Activity Index, 34 +/- 14) with 9 mg daily of CIR budesonide through the Hospital for Sick Children, University of Toronto, Inflammatory Bowel Diseases program.. At first follow-up visit 8.7 +/- 6.0 weeks later, 19 of 32 (59%) were judged by the physician to have responded. In the subset of 22 patients who had laboratory tests repeated at the first follow-up visit, their Pediatric Crohn Disease Activity Index fell from 33 +/- 14 to 22 +/- 16 (P = 0.001). The Pediatric Crohn Disease Activity Index score fell to less than 15 (cut-off score remission) in 29%. Six prepubertal responders continued to receive 6 mg CIR budesonide for 6 to 13 months. Five of the 6 experienced only mild or no gastrointestinal symptoms and gained weight. Nevertheless, their mean height velocity was only 2.3 +/- 1.0 cm/year, and none grew at a rate of more than 4cm/year whilst receiving CIR budesonide.. These data provide grade III evidence of modest effectiveness of CIR budesonide in children with active Crohn disease confined to the ileum with or without right colon involvement. The subnormal growth observed with continued therapy is concerning and may reflect either inadequately controlled intestinal inflammation or direct suppression of linear growth, as is observed with conventional corticosteroids. Randomized controlled pediatric trials of CIR budesonide must include parameters of linear growth as an outcome variable.

Topics: Adolescent; Anti-Inflammatory Agents; Body Height; Budesonide; Crohn Disease; Female; Growth; Humans; Longitudinal Studies; Male; Remission Induction; Retrospective Studies; Severity of Illness Index; Time Factors; Treatment Outcome; Weight Gain

Topics: Administration, Oral; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Drug Approval; Humans; United States; United States Food and Drug Administration

1. Joint pain is a frequent manifestation of Crohn's disease. Budesonide controlled ileal release (CIR) is a predominantly topically acting glucocorticosteroid, which is effective in treating active ileal or ileocaecal Crohn's disease. 2. Therefore, it was of interest to study the effect of this predominantly topically acting therapy on the treatment of an extraintestinal symptom of Crohn's disease by analysing data collected from budesonide CIR (Entocort; Astra Draco AB, Lund, Sweden) trials. 3. Three large studies of budesonide CIR treatment in active Crohn's disease provided a reliable source of clinical data. Of the 611 patients treated in the prospective double-blind controlled trials, 291 had joint pain (arthritis/arthralgia) at entry, which was recorded as part of the Crohn's Disease Activity Index. Statistical analysis was based on all patients treated, provided that the patient had joint pain at the start of treatment. 4. Daily oral budesonide CIR (9mg) resulted in clinical remission of joint pain in 74% (95% confidence intervals (CI) 67-82%) of patients. This outcome was nearly twice as good as placebo (41%; 95% CI 34-57%) and as good as the outcome effected by daily oral prednisolone (40mg; 72%; 95% CI 60-84%). The favourable response to budesonide CIR (9 mg) did not correlate with glucocorticosteroid-associated side effects or with adrenal suppression, which were half those in the prednisolone (40 mg/day) group. 5. The favourable outcome may relate to restitution of normal intestinal immune function.

Topics: Administration, Oral; Administration, Topical; Adrenal Glands; Anti-Inflammatory Agents; Arthralgia; Budesonide; Crohn Disease; Delayed-Action Preparations; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Ileum; Male; Multicenter Studies as Topic; Prospective Studies; Randomized Controlled Trials as Topic; Remission Induction; Severity of Illness Index; Treatment Outcome

Topics: Anti-Inflammatory Agents; Budesonide; Clinical Trials as Topic; Crohn Disease; Humans; Recurrence; Treatment Outcome

Topics: Administration, Oral; Adult; Adverse Drug Reaction Reporting Systems; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Crohn Disease; Drug Hypersensitivity; Female; Glucocorticoids; Humans; Mesalamine

The risk for thrombotic events is increased in inflammatory bowel disease. The factors responsible for such a risk are poorly defined. Recently, an elevated homocysteine level is emerging as a risk factor for thrombosis. The aim of this study was to determine the levels of homocysteine in a well-characterized population of patients with Crohn's disease and to compare it to controls.. The levels of homocysteine were determined in 105 well-characterized patients with Crohn's disease and 106 controls. The levels of folate and B12, which are involved in the metabolism of homocysteine were determined as well. Patients were treated with steroid preparations only.. Homocysteine levels were significantly elevated in the patient population. Elevated levels were correlated with both low B12 and folate levels, but folate deficiency turned out to be a more important factor. Low B12 levels were in correlation with the involvement of the terminal ileum. No correlation was found between homocysteine levels and either disease activity or involvement of the terminal ileum.. Homocysteine levels are increased in patients with Crohn's disease and this finding is inversely correlated with folate levels. Supplementation of folate to patients with Crohn's disease may be warranted.

Topics: Adult; Aged; Anti-Inflammatory Agents; Budesonide; Case-Control Studies; Crohn Disease; Female; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Male; Middle Aged; Prednisone; Risk Factors; Thromboembolism; Time Factors; Vitamin B 12

Topics: Acute Disease; Anti-Inflammatory Agents; Antibodies, Monoclonal; Azathioprine; Budesonide; Chronic Disease; Colectomy; Colitis, Ulcerative; Crohn Disease; Cyclosporine; Drug Combinations; Gastrointestinal Agents; Glucosamine; Humans; Immunosuppressive Agents; Infliximab; Sulfasalazine

Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Azathioprine; Budesonide; Crohn Disease; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Immunosuppressive Agents; Mesalamine; Multicenter Studies as Topic; Prednisolone; Remission Induction

Topics: Administration, Topical; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Budesonide; Crohn Disease; Glucocorticoids; Humans; Mesalamine; Tumor Necrosis Factor-alpha

Topics: Budesonide; Crohn Disease; Glucocorticoids; Humans; Steroids

Topics: Anti-Inflammatory Agents; Budesonide; Clinical Protocols; Colitis, Ulcerative; Crohn Disease; Guidelines as Topic; Humans; Netherlands; Pharmacopoeias as Topic; Prednisolone

Topics: Anti-Inflammatory Agents; Budesonide; Chronic Disease; Colitis, Ulcerative; Crohn Disease; Humans; Inflammatory Bowel Diseases

Topics: Administration, Oral; Adolescent; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Delirium; Female; Glucocorticoids; Humans; Prednisone

Topics: Adolescent; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Humans; Hypokalemia; Male; Potassium; Pregnenediones

Recently, we have shown that administration of adrenocorticotropic hormone (ACTH) to corticosteroid-treated Crohn's disease (CD) patients increased the peripheral blood natural killer (NK) cell activity which was suppressed by the corticosteroids. To elucidate this observation we analysed the in vitro effect of budesonide, prednisolone, cortisol, and ACTH on NK cells of healthy volunteers and corticosteroid-treated CD patients. Incubation of peripheral blood mononuclear cells (PBMNC) from healthy volunteers during the cytotoxicity assay caused a dose-dependent inhibition of NK cell activity by the three corticosteroids, while ACTH had hardly any effect. Pre-incubation for 18 h with high and low inhibiting concentrations also showed a significant inhibiting effect on NK cell activity of the corticosteroids. The percentage of CD56+ NK cells tended to increase after pre-incubation with a high inhibiting concentration of budesonide, prednisolone, and cortisol. Incubation of budesonide- or prednisolone-suppressed PBMNC from healthy volunteers and CD patients, with ACTH and/or cortisol, to mimic the in vivo situation, did not restore the corticosteroid-induced suppression of NK cell activity. The increase of the budesonide- or prednisolone-suppressed NK cell activity after in vivo administration of ACTH to the CD patients is therefore probably not a direct effect of cortisol or ACTH. Presumably other factors like cytokines and/or neurohormones must be involved in the in vivo interaction between corticosteroids, ACTH, and NK cells.

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Adult; Budesonide; Crohn Disease; Female; Humans; Hydrocortisone; Killer Cells, Natural; Male; Middle Aged; Prednisolone; Pregnenediones

Budesonide is a topical steroid which after intestinal absorption is rapidly degraded into inactive metabolites in the liver. Its systemic bioavailability is only 10-15%. In the present open trial the efficiency and safety of oral pH-modified release budesonide were assessed in patients with active Crohn's ileocolitis. This report describes the results of the first 30 of 78 patients. After 6 weeks of treatment with 3 x 3 mg budesonide/day 67% of the patients were in clinical remission. Typical steroid-related side effects were observed in only one patient. Budesonide therefore seems to be suited as an alternative for classical steroids in patients with Crohn's ileocolitis. Its clinical efficacy is comparable with classical steroids but it's rate of steroid-related side effects is lower.

Topics: Administration, Oral; Adult; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Hydrogen-Ion Concentration; Male; Pregnenediones; Treatment Outcome

Patients with chronic active Crohn's disease are dependent on systemic glucocorticosteroids. The aim of the study was to investigate the efficacy of budesonide, a topically selective glucocorticosteroid, as therapy in these patients. We investigated 20 patients with chronic active Crohn's disease. During the last 6 months prior to the study the patients had a median Crohn's disease activity index (CDAI) of 193 (interquartile range: 122-230) (monthly controls) with a median prednisolone dosage of 14 mg per day (9-20). Budesonide was given 3 to 6 mg daily and prednisolone was weaned within one month. The patients were seen monthly for 6 months. Treatment was considered not successful, if under budesonide therapy CDAI was above 200 and increased more than 60 points despite weaning of prednisolone. Only 5 patients remained in the study for 6 months without deterioration. All other patients (75%) dropped out. The reasons for drop out of the study were worsening in 11 cases, the occurrence of extraintestinal manifestations without signs of severe intestinal inflammation in one case and noncompliance in 3 cases. Worsening could be confirmed by an increase not only of CDAI but also of biochemical parameters of inflammation in all cases. Our data show clearly, that in the dosage investigated budesonide was not effective in chronic active Crohn's disease. Further investigations are needed to evaluate higher dosages of budesonide versus conventional glucocorticosteroids.

Topics: Administration, Oral; Adolescent; Adult; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Pilot Projects; Prednisolone; Pregnenediones; Recurrence; Treatment Outcome

Topics: Anti-Inflammatory Agents; Budesonide; Crohn Disease; Drugs, Investigational; Humans; Prednisolone; Pregnenediones

Topics: Administration, Oral; Administration, Topical; Anti-Inflammatory Agents; Budesonide; Colitis, Ulcerative; Crohn Disease; Enema; Glucocorticoids; Humans; Pregnenediones

Topics: Budesonide; Crohn Disease; Glucocorticoids; Humans; Prednisolone; Pregnenediones

Topics: Administration, Oral; Budesonide; Crohn Disease; Delayed-Action Preparations; Glucocorticoids; Humans; Pilot Projects; Pregnenediones