pulmicort and Inflammatory-Bowel-Diseases

The purpose of this expert review is to summarize the diagnosis and management of refractory celiac disease. It will review evaluation of patients with celiac disease who have persistent or recurrent symptoms, differential diagnosis, nutritional support, potential therapeutic options, and surveillance for complications of this condition.. This expert review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology. These Best Practice Advice (BPA) statements were drawn from a review of the published literature and from expert opinion. Since systematic reviews were not performed, these BPA statements do not carry formal ratings of the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: In patients believed to have celiac disease who have persistent or recurrent symptoms or signs, the initial diagnosis of celiac disease should be confirmed by review of prior diagnostic testing, including serologies, endoscopies, and histologic findings. BEST PRACTICE ADVICE 2: In patients with confirmed celiac disease with persistent or recurrent symptoms or signs (nonresponsive celiac disease), ongoing gluten ingestion should be excluded as a cause of these symptoms with serologic testing, dietitian review, and detection of immunogenic peptides in stool or urine. Esophagogastroduodenoscopy with small bowel biopsies should be performed to look for villous atrophy. If villous atrophy persists or the initial diagnosis of celiac disease was not confirmed, consider other causes of villous atrophy, including common variable immunodeficiency, autoimmune enteropathy, tropical sprue, and medication-induced enteropathy. BEST PRACTICE ADVICE 3: For patients with nonresponsive celiac disease, after exclusion of gluten ingestion, perform a systematic evaluation for other potential causes of symptoms, including functional bowel disorders, microscopic colitis, pancreatic insufficiency, inflammatory bowel disease, lactose or fructose intolerance, and small intestinal bacterial overgrowth. BEST PRACTICE ADVICE 4: Use flow cytometry, immunohistochemistry, and T-cell receptor rearrangement studies to distinguish between subtypes of refractory celiac disease and to exclude enteropathy-associated T-cell lymphoma. Type 1 refractory celiac disease is characterized by a normal intraepithelial lymphocyte population and type 2 is defined by the presence of an aberrant, clonal intraepithelial lymphocyte population. Consultation with an expert hematopatholog

Topics: Albumins; Atrophy; Budesonide; Celiac Disease; Enteropathy-Associated T-Cell Lymphoma; Glutens; Humans; Inflammatory Bowel Diseases; Lactose; Micronutrients; Prednisone; Receptors, Antigen, T-Cell; United States

Primary eosinophilic colitis (EC) in adults is a rare and poorly studied disease, with 3 case series, 2 database-based studies and 52 case reports published to date.. Retrospective study of all adult EC cases diagnosed in a large tertiary hospital (Hospital Clínico San Carlos, Madrid) between 2006 and 2016. We included all cases with a histopathological diagnosis of EC and we selected only those cases that were clinically recognized primary EC. We report their clinical, endoscopic and histopathological features and review the literature on this topic.. We identified 22 primary EC cases. Patients were mostly women (77%) with a mean age of 41 years. 4 patients (18%) had coexistent allergic diseases. Most patients consulted with diarrhea (86%) and 3 patients also suffered from rectal bleeding. Blood tests showed peripheral eosinophilia in 4 cases (18%). 19 patients had no endoscopic lesions, 2 had features of unspecific colitis and one showed features suggestive of IBD. Mean and maximum number of eosinophils per high power field ranged from 16 to 199 and 20 to 253 (mean: 48 and 70). They were mainly located in the lamina propria and most cases were associated with signs of eosinophil activation. Most patients were treated by corticosteroids, diet or budesonide and the result of treatment was generally good. No complications or recurrences were reported.. EC etiology and pathogenesis is unknown. Its clinical, endoscopical and imaging features are not specific, and clear histopathological criteria are lacking. Identification of signs of eosinophilic activation could be helpful.

Topics: Budesonide; Colitis; Colon; Diarrhea; Eosinophilia; Humans; Inflammatory Bowel Diseases

The connection between a dysregulated gut-associated lymphoid tissue and IgA nephropathy (IgAN) was supposed decades ago after the observation of increased association of IgAN with celiac disease. Pivotal studies have shown a role for alimentary antigens, particularly gliadin in developing IgAN in BALB/c mice, and a reduction in IgA antigliadin antibodies and proteinuria was reported after gluten free-diet in patients with IgAN. Recently a genome-wide association study showed that most loci associated with IgAN also are associated with immune-mediated inflammatory bowel diseases, maintenance of the intestinal barrier, and response to gut pathogens. Transgenic mice that overexpress the B-cell activating factor develop hyper-IgA with IgAN modulated by alimentary components and intestinal microbiota. Mice expressing human IgA1 and a soluble form of the IgA receptor (sCD89) develop IgAN, which is regulated by dietary gluten. Recent observations have confirmed gut-associated lymphoid tissue hyper-reactivity in IgAN patients with IgA against alimentary components. Interesting results were provided by the NEFIGAN randomized controlled trial, which adopted an enteric controlled-release formulation of the corticosteroid budesonide targeted to Peyer's patches. After 9 months of treatment, a reduction in proteinuria was observed with stabilized renal function and limited adverse events. The gut-renal connection is an area of promising new treatment approaches for patients with IgAN.

Topics: Animals; Antibodies; Budesonide; Celiac Disease; Comorbidity; Gastrointestinal Microbiome; Gliadin; Glomerulonephritis, IGA; Glucocorticoids; Glutens; Humans; Immunoglobulin A; Inflammatory Bowel Diseases; Intestinal Mucosa; Intestines; Lymphoid Tissue; Mice; Mice, Inbred BALB C; Mice, Transgenic; Peyer's Patches; Proteinuria; Receptors, Fc

For many women with inflammatory bowel disease (IBD), the illness coincides with their childbearing years. IBD increases the risk of pregnancy complications and adverse pregnancy outcomes. The multidisciplinary care team should emphasize the importance of medication adherence to achieve preconception disease control and maintain corticosteroid-free remission throughout pregnancy. Medication adjustments to reduce fetal exposure may be considered on an individualized basis in quiescent disease; however, any benefits of such adjustments remain theoretic and there is risk of worsening disease activity. Mode of delivery is determined by obstetric indications, except for women with active perianal disease who should consider cesarean delivery.

Topics: Adalimumab; Aminosalicylic Acids; Anti-Bacterial Agents; Antibodies, Monoclonal; Biological Products; Breast Feeding; Budesonide; Certolizumab Pegol; Delivery, Obstetric; Female; Gastrointestinal Agents; Glucocorticoids; Humans; Immunosuppressive Agents; Infertility, Female; Infertility, Male; Inflammatory Bowel Diseases; Infliximab; Male; Natalizumab; Prednisone; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnancy Rate

Microscopic colitis (MC) is a chronic inflammatory bowel disease that has emerged in the last three decades as a leading cause of chronic watery diarrhoea. MC classically includes two main subtypes: lymphocytic colitis (LC) and collagenous colitis (CC). Other types of histopathological changes in the colonic mucosa have been described in patients with chronic diarrhoea, without fulfilling the conventional histopathological criteria for MC diagnosis. Whereas those unclassified alterations remained orphan for a long time, the use of the term incomplete MC (MCi) is nowadays universally accepted. However, it is still unresolved whether CC, LC and MCi should be considered as one clinical entity or if they represent three related conditions. In contrast to classical MC, the real epidemiological impact of MCi remains unknown, because only few epidemiological studies and case reports have been described. MCi presents clinical characteristics indistinguishable from complete MC with a good response to budesonide and cholestiramine. Although a number of medical treatments have been assayed in MC patients, currently, there is no causal treatment approach for MC and MCi, and only empirical strategies have been performed. Further studies are needed in order to identify their etiopathogenic mechanisms, and to better classify and treat MC.

Topics: Biopsy; Budesonide; Cholestyramine Resin; Colitis, Collagenous; Colitis, Lymphocytic; Collagen; Colon; Diagnosis, Differential; Diarrhea; Humans; Immunohistochemistry; Inflammatory Bowel Diseases; Intestinal Mucosa; Sex Factors

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

In 2013, several new IBD drugs, including golimumab and vedolizumab, have been approved or completed successful programmes, showing efficacy in both Crohn’s disease and ulcerative colitis. In addition, classic IBD drugs have been formulated for colonic delivery, such as budesonide MMX®, which was recently approved for mild-to-moderate ulcerative colitis.

Topics: Anti-Inflammatory Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Biological Factors; Budesonide; Humans; Inflammatory Bowel Diseases; Treatment Outcome

At present, therapy of inflammatory bowel disease is still far from being fully satisfactory; old drugs like steroids, for instance, still represent a cornerstone in the treatment of active disease despite their associated important side effects and incomplete clinical efficacy. In the last years, new therapeutic strategies have been suggested in order to avoid or at least limit steroids use and in this direction the so-called low bioavailability steroids appeared to be a promising therapeutic weapon; however, some grey areas about their real utility and manner of use still remain. The aim of this review is to evaluate the available evidence about the use of oral budesonide and beclomethasone dipropionate in inflammatory bowel disease, to critically assess their current position in the therapeutic algorithm of these diseases and to give simple and practical indications for their use in every-day clinical practice.

Topics: Beclomethasone; Biological Availability; Budesonide; Glucocorticoids; Humans; Inflammatory Bowel Diseases

Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases that have been treated with corticosteroids, 5-aminosalicates and thiopurines, but therapeutic options have been broadened with the arrival of anti-tumor necrosis factor antibodies. In this article we reviewed the current evidence-based approach to inflammatory bowel disease, the modifications that have been made to existing therapies and discussed new drugs that have shown success in clinical trials. The new drugs discussed here are those that disturb lymphocyte homing to the gut (natalizumab, vedolizumab and anti-mucosal addressin cellular adhesion molecule); one that blocks interleukin (IL)-12 as well as the IL-23/T helper 17 (Th17) axis (ustekinumab) and one that blocks the signaling of multiple cytokines (tofacitinib).

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Budesonide; Certolizumab Pegol; Evidence-Based Practice; Humans; Immunoglobulin Fab Fragments; Inflammatory Bowel Diseases; Mesalamine; Polyethylene Glycols; Rifamycins; Rifaximin; Ustekinumab

Systemic corticosteroids have been used to treat active inflammatory bowel disease for over 50 years by virtue of their unquestionable efficacy in inducing clinical remission rapidly in the vast majority of patients. Nevertheless, traditional corticosteroids are associated to a plethora of potentially serious side effects due to their systemic metabolism; for this reason, interest has lately been growing in newer steroid compounds characterized by a high topical anti-inflammatory activity and a low systemic bioavailability. These compounds, namely budesonide and beclomethasone dipropionate--regarding the treatment of inflammatory bowel disease--can be administered orally and thanks to sophisticated delivery systems are conveyed specifically to the inflamed gut mucosa where they exert their anti-inflammatory action. After intestinal absorption, these drugs are promptly and efficiently inactivated by the liver, so that only inactive molecules reach the systemic circulation. This review revises the main clinical trials, meta-analyses and observational studies conducted on traditional and newer steroids, and critically interprets the main results achieved by these studies.

Topics: Beclomethasone; Biological Availability; Budesonide; Glucocorticoids; Humans; Inflammatory Bowel Diseases

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

Diarrhea is a common clinical feature of inflammatory bowel diseases and may be accompanied by abdominal pain, urgency, and fecal incontinence. The pathophysiology of diarrhea in these diseases is complex, but defective absorption of salt and water by the inflamed bowel is the most important mechanism involved. In addition to inflammation secondary to the disease, diarrhea may arise from a variety of other conditions. It is important to differentiate the pathophysiologic mechanisms involved in the diarrhea in the individual patient to provide the appropriate therapy. This article reviews microscopic colitis, ulcerative colitis, and Crohn's disease, focusing on diarrhea.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Antidiarrheals; Bacterial Infections; Biopsy; Bismuth; Blood Cell Count; Blood Chemical Analysis; Body Water; Breath Tests; Budesonide; Cholestyramine Resin; Colitis, Microscopic; Diarrhea; Drug-Related Side Effects and Adverse Reactions; Endoscopy, Gastrointestinal; Feces; Glucocorticoids; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Intestinal Absorption; Intestinal Fistula; Intestinal Mucosa; Intestines; Ion Transport; Malabsorption Syndromes; Medical History Taking; Mesalamine; Organometallic Compounds; Physical Examination; Postoperative Complications; Prednisolone; Salicylates; Sodium; Tumor Necrosis Factor-alpha

The aim of this article is to review current evidence-based approaches to treatment of ulcerative colitis and Crohn's disease.. The primary goal of treatment is to induce and to maintain remission in a safe and efficacious fashion. The 5-aminosalicylic acid (5-ASA) agents and oral steroids remain the first-line approach for the treatment of ulcerative colitis and Crohn's disease. The 'step-up' approach includes the use of immunomodulators [azathioprine (AZA), or 6-mercaptopurine (6-MP)] and newer biologic agents (infliximab, adalimumab, and natalizumab). The 'step-down' approach can also be considered individually on the basis of the severity of Crohn's disease.. Current treatment regimens still involve medications with well known efficacy and safety profiles and progress to more potent treatments such as immunomodulators and biologic agents. Adverse events of potent treatment with biologics and immunomodulators have been recognized. In some cases, aggressive approaches with the use of more potent agents as first-line therapy has been proposed, but they are still not considered a routine approach.

Topics: Adrenal Cortex Hormones; Aminosalicylic Acids; Anti-Inflammatory Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Azathioprine; Budesonide; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Infliximab; Mercaptopurine; Natalizumab

Inflammatory bowel disease, including Crohn's disease and ulcerative colitis, features recurrent episodes of inflammation of the GI tract. The treatment of inflammatory bowel disease is aimed at breaking the cycle of relapsing and remitting inflammation by inducing and maintaining remission. Systemically active conventional corticosteroids have long played a role in the induction of remission in both Crohn's disease and ulcerative colitis, however, their long-term use can lead to adverse systemic effects. Budesonide, a synthetic steroid, has potent local anti-inflammatory effects and limited systemic bioavailability making it an appealing therapeutic option. Ulcerative colitis with predominantly distal disease may be treated with topical budesonide, however, novel oral controlled-release formulations have also been developed to allow for treatment of the entire colon. This article summarizes the use of budesonide in the management of inflammatory bowel disease.

Topics: Adrenal Cortex Hormones; Animals; Anti-Inflammatory Agents; Budesonide; Clinical Trials as Topic; Drug Administration Routes; Drug Delivery Systems; Gastrointestinal Tract; Humans; Inflammatory Bowel Diseases; Precision Medicine; Remission Induction

The therapy for posttransplant IBD is clinically challenging. Patients receiving liver transplants are immunosuppressed to prevent rejection, but via an unknown mechanism develop de novo IBD in spite of receiving some of the same medications used for therapy in traditional IBD. In the published literature most of the patients who developed de novo IBD were treated with traditional corticosteroids. Exposure to systemic corticosteroids increases risks of infection, diabetes mellitus, and osteoporosis among other complications. Budesonide, a luminally active steroid with low systemic absorption, is an established therapeutic agent for IBD that should receive special considerations as first-line therapy in this patient population.. We describe 3 cases of de novo IBD after liver transplantation. None of these patients had a history of IBD prior to their transplant. All 3 were treated with oral budesonide in lieu of systemic corticosteroids. Additionally, a Medline MeSH search was performed using the terms "inflammatory bowel disease" and "liver transplant" as part of a systematic review of the literature.. All 3 cases of de novo post transplant IBD went into clinical remission with oral budesonide. The Medline search ultimately revealed 19 case reports, case series or retrospective reviews on de novo post liver transplant IBD. Most reports focused on the diagnosis and risk factors and did not have an emphasis on therapy.. Given the track record for budesonide in traditional IBD, and its documented efficacy and systemic steroid-sparing benefit, in our opinion this drug should be considered first-line therapy for de novo posttransplant IBD.

Topics: Administration, Oral; Budesonide; Cytomegalovirus; Cytomegalovirus Infections; Female; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Liver Transplantation; Male; Middle Aged; Postoperative Complications

Crohn's disease and ulcerative colitis are chronic relapsing inflammatory bowel diseases with extremely great variability in presentation and clinical course. For many decades, corticosteroids and aminosalicylates have been the mainstay of the treatment for both Crohn's disease and ulcerative colitis, for the induction and maintenance of remission, respectively. The main limiting factors for the repeated use of corticosteroids or the use as a maintenance treatment are the very high prevalence of systemic side effects, together with the possibility of developing dependency on and/or resistance to the drug, which are reported in more than one third of patients with inflammatory bowel disease. In the last decade, a number of corticosteroids with enhanced topical activity and low systemic activity have been developed. Among them, budesonide and beclomethasone dipropionate are the most used for the treatment of the inflammatory bowel diseases. Indeed, budesonide is the drug of choice for the treatment of ileo(-cecal) active Crohn's disease with mild-to-moderate activity, due to controlled ileal release. Budesonide foam and/or enemas are also efficacious in the treatment of left-sided/distal ulcerative colitis. Gastro-resistant, extended release tablets characterized by a multimatrix structure (i.e. MMX-budesonide), have also been developed to allow uniform release along the length of the colon. This paper reviews the mechanism-of-action, safety and efficacy of budesonide in the treatment of inflammatory bowel disease.

Topics: Aging; Budesonide; Humans; Inflammatory Bowel Diseases; Randomized Controlled Trials as Topic; Recurrence; Remission Induction

Topics: Administration, Oral; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Inflammatory Agents; Beclomethasone; Budesonide; Controlled Clinical Trials as Topic; Cushing Syndrome; Delayed-Action Preparations; Double-Blind Method; Fluticasone; Humans; Inflammatory Bowel Diseases; Intestinal Absorption; Meta-Analysis as Topic; Randomized Controlled Trials as Topic; Remission Induction

Budesonide is a promising drug for a variety of documented applications and has potential in gastroenterology. Its unique local mechanism of delivery and efficient first-pass metabolism, resulting in fewer systemic adverse effects than with conventional glucocorticoids, makes this a desirable drug for clinical practice. This drug has shown promise in treating a wide spectrum of inflammatory diseases from inflammatory bowel disease and other colitides to autoimmune liver diseases. Future research should focus on ways to increase delivery methods to promote long-term usage for maintenance therapy for the disease entities listed above, as well as for other potential nongastrointestinal conditions.

Topics: Administration, Oral; Budesonide; Delayed-Action Preparations; Glucocorticoids; Humans; Inflammatory Bowel Diseases; Molecular Structure

Budesonide is a glucocorticoid with high topical glucocorticoid activity and low systemic availability. Oral pH-modified release budesonide has been investigated for the treatment of various inflammatory intestinal diseases.. To summarise the investigational data of oral pH-modified release budesonide for the treatment of Crohn's disease, ulcerative colitis, collagenous colitis and lymphocytic colitis.. Assessment of all published (full paper or meeting abstract) clinical studies with oral pH-modified release budesonide for the treatment of inflammatory intestinal diseases.. Oral pH-modified release budesonide induces remission in mild-to-moderately active Crohn's disease of the ileum and/or ascending colon. This drug is useful to replace conventional systemic glucocorticoids in patients with ileocoecal Crohn's disease. Open-label studies showed efficacy in ulcerative colitis, but this finding has to be confirmed in controlled trials. Oral pH-modified release budesonide is also effective for the treatment of collagenous colitis and lymphocytic colitis.

Topics: Administration, Oral; Anti-Inflammatory Agents; Budesonide; Clinical Trials as Topic; Colitis, Collagenous; Colitis, Lymphocytic; Delayed-Action Preparations; Glucocorticoids; Humans; Hydrogen-Ion Concentration; Inflammatory Bowel Diseases

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

Corticosteroids are a mainstay in the treatment of inflammatory bowel disease. Administered topically, orally, or intravenously corticosteroids rapidly and consistently improve moderate to severe active ulcerative colitis and Crohn's disease, although they are ineffective in the maintenance of remission in either illness. The beneficial effects of corticosteroid therapy are counterbalanced by their many side effects. A better understanding of the mechanism of steroid action and toxicity has led to the development of novel corticosteroids that offer the promise of continued efficacy with minimal toxicity. This article reviews the role of conventional and novel corticosteroids in the management of inflammatory bowel disease.

Topics: Adrenal Cortex Hormones; Budesonide; Humans; Inflammatory Bowel Diseases; Randomized Controlled Trials as Topic

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

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

Budesonide is a synthetic glucocorticoid used in the Crohns's disease (CD) and ulcerative colitis (UC). The aim of the study was to evaluate its efficacy in inducing and maintaining remission of CD in oral administration and in inducing endoscopic and histologic remission in distal UC when was given as enema.. Systematic review of controlled clinical trials was made and meta-analysis were performed using the Peto method. Eight studies provided data regarding CD (4 in induction of remission and 4 in maintenance therapy) and 4 regarding UC.. CD-inducing remission: in total 560 patients were involved; 280 received 9 mg/d of budesonide and 280 received 40-46 mg/d of prednisolone. Clinical remission was similar in both groups [0.76 (0.54-1.06)] [0R (CI 95%)] and adverse events were more frequent in patients treated with prednisolone [0.42 (0.30-0.58)]. Plasma cortisol was evaluated in 292 patients (146 each group); values were significantly lower in prednisolone group [0.32 (0.20-0.50)]. CD-maintaining remission: in total 449 patients were enrolled; 174 and 90 received 3 mg/d or 6 mg/d of budesonide respectively and 185 received placebo. There were not significant differences between placebo and budesonide 3 mg/d [1.04 (0.56-1.92)]. Budesonide 6 mg/d was also similar to placebo group [0.91 (0.59-1.39)]. UC: 325 patients were included, 156 received budesonide and 169 were given conventional glucocorticoids. No significant differences were found between both groups in endoscopic remission rates [1.15 (0.71-1.88)].. Budesonide is as useful as prednisolone in treatment of active CD and it has a lower impact in serum cortisol levels. Nevertheless, at evaluated dose, it is not useful for maintenance therapy. In UC is as effective as conventional glucocorticoids.

Topics: Anti-Inflammatory Agents; Budesonide; Clinical Trials as Topic; Glucocorticoids; Humans; Inflammatory Bowel Diseases

Measurements of luminal pH in the normal gastrointestinal tract have shown a progressive increase in pH from the duodenum to the terminal ileum, a decrease in the caecum, and then a slow rise along the colon to the rectum. Some data in patients with ulcerative colitis suggest a substantial reduction below normal values in the right colon, while limited results in Crohn's disease have been contradictory. Determinants of luminal pH in the colon include mucosal bicarbonate and lactate production, bacterial fermentation of carbohydrates and mucosal absorption of short chain fatty acids, and possibly intestinal transit. Alterations in these factors, as a result of mucosal disease and changes in diet, are likely to explain abnormal pH measurements in inflammatory bowel disease (IBD). It is conceivable that reduced intracolonic pH in active ulcerative colitis impairs bioavailability of 5-aminosalicylic acid from pH dependent release formulations (Asacol, Salofalk) and those requiring cleavage by bacterial azo reductase (sulphasalazine, olsalazine, balsalazide), but further pharmacokinetic studies are needed to confirm this possibility. Reports that balsalazide and olsalazine may be more efficacious in active and quiescent ulcerative colitis, respectively, than Asacol suggest that low pH may be a more critical factor in patients taking directly pH dependent release than azo bonded preparations. Reduced intracolonic pH also needs to be considered in the development of pH dependent colonic release formulations of budesonide and azathioprine for use in ulcerative and Crohn's colitis. This paper reviews methods for measuring gut pH, its changes in IBD, and how these may influence current and future therapies.

Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Azathioprine; Biological Availability; Budesonide; Catheterization; Electrodes; Humans; Hydrogen-Ion Concentration; Immunosuppressive Agents; Inflammatory Bowel Diseases; Mesalamine; Reference Values; Telemetry

Different orally and rectally applicable forms of 5-ASA and budesonide have been developed to achieve sufficient high concentrations of the active moieties at the site of inflammation (small and/or large bowel) and to limit the systemic action of the drugs. This concept of drug targeting could be accomplished by both special galenic formulations and by utilizing the pharmacokinetic properties of the agents especially their high intestinal and hepatic presystemic elimination. Thus, 5-ASA and budesonide represent drugs of first choice in the treatment of Crohn's disease and ulcerative colitis. This review describes the various pharmacokinetic and (patho)physiologic factors and their impact on drug delivery and biological availability of the different 5-ASA and budesonide preparations.

Topics: Budesonide; Drug Delivery Systems; Humans; Inflammatory Bowel Diseases; Mesalamine; Structure-Activity Relationship

To increase the therapeutic efficiency of the drugs used for inflammatory bowel disease(IBD), DDS technology is useful. Drugs used for IBD are glucocorticosteroids and 5-aminosalicylic acid(5-ASA) and its derivatives. DDS preparations of these drugs are classified according to their delivery mechanisms, i.e., chemical DDS, sustained release DDS and colon delivery system. Recent development of DDS technology has enabled the colon delivery of these drugs. They are 1)pH sensitive device, 2) time-controlled device, 3)polymer coating device that is degradable by intestinal microflora and 4)pressure-controlled device. Several DDS preparations of prednisolone and 5-ASA and their pharmacokinetic characteristics are described precisely.

Topics: Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Capsules; Delayed-Action Preparations; Drug Delivery Systems; Humans; Hydrogen-Ion Concentration; Inflammatory Bowel Diseases; Mesalamine; Prednisolone; Prodrugs

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

Inflammatory bowel diseases are treated in some cases by local administration of anti-inflammatory drugs. Local delivery of drugs in the colon following oral administration may lead to improved efficacy/side-effect profiles and may improve patient compliance. This review covers a number of issues important in the design of oral delivery systems of glucocorticosteroids for local therapy of colonic inflammation. The choice of specific glucocorticosteroids is based on the drug's physicochemical and pharmacological properties. The conditions under which an orally administered glucocorticosteroid (or other drug) must be delivered to treat ulcerative colitis are also discussed. These conditions include variations in local pH, transit throughout the gastrointestinal tract, the potential role of gut microflora, and drug dissolution in both the healthy and diseased large intestine. The effective delivery of topically-active glucocorticosteroids in ulcerative colitis and Crohn's colitis patients is complex, but if successful could improve their usefulness.

Topics: Administration, Oral; Administration, Rectal; Anti-Inflammatory Agents; Area Under Curve; Budesonide; Gastric Emptying; Glucocorticoids; Half-Life; Humans; Inflammatory Bowel Diseases

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

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

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

The aim of this study was to determine the effect of budesonide on the expression of Ki-67 and PCNA proliferative antigens and the apoptotic index in the course of inflammatory bowel disease (IBD) and to evaluate the applicability of these markers in monitoring IBD treatment in dogs. The experiment was performed on 28 dogs of different breeds and both sexes, with body weight of 6 to 20 kg, aged 6 to 10 years. The animals diagnosed with IBD were divided into four groups of 7 dogs each, including three experimental groups characterized by various severity of IBD and a control group. The dogs from the experimental groups were administered budesonide (Entocort, Astra-Zeneca, Sweden) in daily doses depending on body weight of animal - 1.0 mg (6-10 kg), 1.5 mg (11-15 kg) or 2.0 mg (16-20 kg) and control group dogs were orally administered empty gelatin capsules (placebo) for 30 days. The expression of Ki-67 and PCNA antigens was determined immunohistochemically, and the apoptotic index was expressed as the number of TUNEL-positive lamina propria cells in duodenal, jejunal and colonic mucosa before and after 30 days of budesonide therapy. The results of the study point to the limited applicability of Ki-67 and PCNA proliferation markers and high applicability of the apoptotic index in monitoring IBD progression and treatment in dogs. Budesonide exerted significant anti-apoptotic effects in canine patients with various severity of IBD, which indicates that next-generation glucocorticosteroids can be effectively used in the treatment of gastrointestinal diseases characterized by high values of the apoptotic index, including IBD.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Budesonide; Dog Diseases; Dogs; Female; Gene Expression Regulation; Inflammatory Bowel Diseases; Ki-67 Antigen; Male; Proliferating Cell Nuclear Antigen

This study evaluates the efficacy of budesonide in the treatment of inflammatory bowel disease (IBD) in dogs based on the results of clinical, endoscopic and histopathological examinations. The severity of clinical symptoms was assessed based on CIBDAI scores, and macroscopic and histopathological changes were described in accordance with the recommendations of the WSAVA Gastrointestinal Standardization Group for 2008. The results of the experiment revealed that budesonide does not offer effective treatment for canine IBD. The tested drug failed to alleviate the clinical symptoms of disease, lower CIBDAI scores, or improve the macroscopic appearance of intestinal mucosa. The effectiveness of budesonide was most highly evaluated in the histopathological picture of duodenal, jejunal and colonic mucosa.

Topics: Animals; Budesonide; Dog Diseases; Dogs; Female; Glucocorticoids; Inflammatory Bowel Diseases; Male

To evaluate the pharmacokinetics and clinical efficacy of budesonide in dogs with inflammatory bowel disease (IBD).. 11 dogs (mean ± SD age, 5.7 ± 3.9 years; various breeds and body weights) with moderate or severe IBD.. Each dog received a controlled-release formulation of budesonide (3 mg/m(2), PO, q 24 h) for 30 days (first day of administration was day 1). The concentration of budesonide and its metabolite (16-α-hydroxyprednisolone) was measured via liquid chromatography-tandem mass spectrometry in plasma and urine samples obtained on days 1 and 8 of treatment. On those days, plasma samples were obtained before the daily budesonide administration and 0.5, 1, 2, 4, and 7 hours after drug administration, whereas urine samples were obtained after collection of the last blood sample. A clinical evaluation was performed on the dogs before onset of drug administration and on days 20 and 30 after start of drug administration.. The highest plasma concentration of budesonide and 16-α-hydroxyprednisolone on day 1 was detected at 1 hour and at 2 hours after drug administration, respectively. After standardization on the basis of specific gravity, the ratio between urinary concentrations of budesonide and 16-α-hydroxyprednisolone was 0.006 and 0.012 on days 1 and 8, respectively. The clinical response was adequate in 8 of 11 dogs.. Budesonide was rapidly absorbed and metabolized in dogs with IBD. The drug gradually accumulated, and there was an adequate therapeutic response and no adverse effects.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Budesonide; Chromatography, Liquid; Dog Diseases; Dogs; Female; Glucocorticoids; Inflammatory Bowel Diseases; Male; Prednisolone; Tandem Mass Spectrometry

Our objective was to investigate the changes in circulating glucocorticoid bioactivity (GBA) at the onset of systemic glucocorticoid therapy in pediatric patients with inflammatory bowel disease.. Prednisolone (1 mg/kg/d) or budesonide (9 mg/d) was introduced as a single daily dose, and the patients (n=22) were subsequently followed up at 2 to 4 week intervals. The limit for a raised value of serum GBA was defined in pediatric patients (mean+2 SD; 118 nM cortisol equivalents; n=142).. Two weeks of prednisolone brought about an increase in serum GBA from 84+/-14 to 336+/-38 nM cortisol equivalents (mean+/-SE; P<0.001). Young patients (<10 y) had similar GBA values to older patients, even though their prednisolone dose was higher (1.3 vs. 0.79 mg/kg; P<0.05). Patients treated with budesonide displayed a minor increase in GBA (151+/-20 vs. 267+/-21 nM cortisol equivalents after 4 wk of treatment; P<0.05; n=3), and when switched to prednisolone (n=2), their GBA level increased 3-fold. GBA levels did not predict the development of glucocorticoid-related side effects.. Prednisolone doses used in the treatment of pediatric inflammatory bowel disease patients elicit a 4-fold increase in serum GBA that is significantly higher than the increase induced by budesonide. The GBA measurement is an additional tool for assessing steroid therapy at an individual level during systemic glucocorticoid treatment.

Topics: Adolescent; Age Factors; Budesonide; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Glucocorticoids; Humans; Hydrocortisone; Inflammatory Bowel Diseases; Male; Prednisolone; Prospective Studies

Inflammatory bowel disease (IBD) represents a group of chronic and debilitating inflammatory diseases affecting various parts of the gastrointestinal (GI) tract. The disease incidence and prevalence have been growing worldwide since the early 21st century and this upward trend is expected to continue. Due to a complex and variable clinical presentation across different patients, the efficacy of a one-size-fits-all commercial formulation for IBD remains limited. Here, we present the development of a novel adjustable and controllable release, 3D printed colonic targeting (CORR3CT) dosage form of budesonide, to reduce off-targeting adverse effects and to potentially replace the use of enemas, which are invasive and commonly associated with poor adherence. An in vitro Gastrointestinal Simulated System (GISS) model was employed in this study to examine the ability of the 3D printed tablets to deliver budesonide to various targeted sites along the gastrointestinal tract. CORR3CT tablet with Pill-in-pill configurations were designed, fabricated and the relationship between the 3D printed design and resultant dissolution profiles were established. The 3D printed tablets also exhibited excellent and comparable dose accuracy and quality versus commercial tablets, while enhancing the delivery of budesonide to the targeted colon region. Overall, this study has laid the foundational proof of concept demonstrating controllable targeting of oral therapeutics along the gastrointestinal tract using 3D printing technologies.

Topics: Budesonide; Colon; Drug Liberation; Humans; Inflammatory Bowel Diseases; Printing, Three-Dimensional; Tablets; Technology, Pharmaceutical

Inflammatory bowel disease (IBD) is one of the most common intestinal disorders, with increasing global incidence and prevalence. Numerous therapeutic drugs are available but require intravenous administration and are associated with high toxicity and insufficient patient compliance. Here, an oral liposome that entraps the activatable corticosteroid anti-inflammatory budesonide was developed for efficacious and safe IBD therapy. The prodrug was produced via the ligation of budesonide with linoleic acid linked by a hydrolytic ester bond, which was further constrained into lipid constituents to form colloidal stable nanoliposomes (termed budsomes). Chemical modification with linoleic acid augmented the compatibility and miscibility of the resulting prodrug in lipid bilayers to provide protection from the harsh environment of the gastrointestinal tract, while liposomal nanoformulation enables preferential accumulation to inflamed vasculature. Hence, when delivered orally, budsomes exhibited high stability with low drug release in the stomach in the presence of ultra-acidic pH but released active budesonide after accumulation in inflamed intestinal tissues. Notably, oral administration of budsomes demonstrated favorable anti-colitis effect with only ∼7% mouse body weight loss, whereas at least ∼16% weight loss was observed in other treatment groups. Overall, budsomes exhibited higher therapeutic efficiency than free budesonide treatment and potently induced remission of acute colitis without any adverse side effects. These data suggest a new and reliable approach for improving the efficacy of budesonide. Our

Topics: Animals; Budesonide; Colitis; Drug-Related Side Effects and Adverse Reactions; Inflammatory Bowel Diseases; Linoleic Acid; Liposomes; Mice; Prodrugs

Inflammatory bowel disease (IBD) is characterized by chronic inflammation along the gastrointestinal tract. For IBD effective treatment, developing an orally administered stable drug delivery system capable of targeting inflammation sites is a key challenge. Herein, we report pH responsive hyaluronic (HA) coated Eudragit S100 (ES) nanoparticles (NPs) for the targeted delivery of budesonide (BUD) (HA-BUD-ES-NPs). HA-BUD-ES-NPs showed good colloidal properties (274.8 ± 2.9 nm and - 24.6 ± 2.8 mV) with high entrapment efficiency (98.3 ± 3.41%) and pH-dependent release profile. The negative potential following incubation in simulated gastrointestinal fluids reflected the stability of HA coat. In vitro studies on Caco-2 cells showed HA-BUD-ES-NPs biocompatibility and enhanced cellular uptake and anti-inflammatory effects as shown by the significant reduction in IL-8 and TNF-α. The oral administration of HA-BUD-ES-NPs in an acetic acid induced colitis rat model significantly mitigated the symptoms of IBD, and improved BUD therapeutic efficacy compared to drug suspension. This was proved via the improvement in disease activity index and ulcer score in addition to refined histopathological findings. Also, the assessment of inflammatory markers, epithelial cadherin, and mi-R21 all reflected the higher efficiency of HA-BUD-ES-NPs compared to free drug and uncoated formulation. We thus suggest that HA-BUD-ES-NPs provide a promising drug delivery platform for the management and site specific treatment of IBD.

Topics: Acetic Acid; Animals; Budesonide; Caco-2 Cells; Cadherins; Colitis; Humans; Hyaluronic Acid; Inflammation; Inflammatory Bowel Diseases; MicroRNAs; Nanoparticles; Rats

The Swiss Autoimmune Hepatitis Cohort Study is a nationwide registry, initiated in 2017, that collects retrospective and prospective clinical data and biological samples from patients of all ages with autoimmune hepatitis treated at Swiss hepatology centres. Here, we report the analysis of the first 5 years of registry data.. A total of 291 patients with autoimmune hepatitis have been enrolled, 30 of whom were diagnosed before 18 years of age and composed the paediatric cohort. Paediatric cohort: median age at diagnosis 12.5 years (range 1-17, interquartile range (IQR) 8-15), 16 (53%) girls, 6 (32%) with type 2 autoimmune hepatitis, 8 (27%) with autoimmune sclerosing cholangitis, 1 with primary biliary cholangitis variant syndrome, 4 (15%) with inflammatory bowel disease and 10 (41%) with advanced liver fibrosis at diagnosis. Adult cohort: median age at diagnosis 54 years (range 42-64, IQR 18-81), 185 (71%) women, 51 (20%) with primary biliary cholangitis variant syndrome, 22 (8%) with primary sclerosing cholangitis variant syndrome, 9 (4%) with inflammatory bowel disease and 66 (32%) with advanced liver fibrosis at diagnosis. The median follow-up time for the entire cohort was 5.2 years (IQR 3-9.3 years). Treatment in children: 29 (97%) children were initially treated with corticosteroids, 28 of whom received combination treatment with azathioprine. Budesonide was used in four children, all in combination with azathioprine. Mycophenolate mofetil was used in five children, all of whom had previously received corticosteroids and thiopurine. Treatment in adults (data available for 228 patients): 219 (96%) were treated with corticosteroids, mostly in combination with azathioprine. Predniso(lo)ne was the corticosteroid used in three-quarters of patients; the other patients received budesonide. A total of 78 (33%) patients received mycophenolate mofetil, 62 of whom had previously been treated with azathioprine. Complete biochemical response was achieved in 13 of 19 (68%) children and 137 of 182 (75%) adults with available follow-up data. All children were alive at the last follow-up, and none had undergone liver transplantation. Five (2%) adults underwent liver transplantation, two of whom had a fulminant presentation. Four (2%) adults with autoimmune hepatitis died (two from liver-associated causes).. Patients with autoimmune hepatitis in Switzerland had clinical features similar to those in other cohorts. The proportion of patients diagnosed with primary biliary cholangitis variant syndrome was higher than expected. Autoimmune hepatitis was managed according to guidelines, except for the use of budesonide in a small proportion of paediatric patients. The outcomes were excellent, but the findings must be confirmed over a longer follow-up period.

Topics: Adolescent; Adult; Azathioprine; Budesonide; Child; Child, Preschool; Cohort Studies; Female; Hepatitis, Autoimmune; Humans; Infant; Inflammatory Bowel Diseases; Liver Cirrhosis; Liver Cirrhosis, Biliary; Male; Middle Aged; Mycophenolic Acid; Prospective Studies; Retrospective Studies; Switzerland

Inflammatory bowel disease (IBD) is related to excessive reactive oxygen species (ROS) and high expression of proinflammatory cytokines. An enzymatically active drug carrier that can simultaneously scavenge excessive ROS and deliver anti-inflammatory drugs to inhibit the production of inflammatory cytokines may lead to improved therapeutic effects. Herein, nanoparticles (NPs) that can target activated macrophages, remove ROS and release anti-inflammatory drugs are fabricated by loading budesonide (Bud) into dextran sulfate sodium (DSS)-coated hollow mesoporous manganese dioxide (hMnO

Topics: Budesonide; Humans; Inflammatory Bowel Diseases; Manganese Compounds; Nanoparticles; Oxides; Reactive Oxygen Species

Azathioprine (AZA)-induced pancreatitis (AIP) is a common, idiosyncratic adverse effect whose incidence and risk factors data in inflammatory bowel disease (IBD) patients are not fully clarified. We aimed to establish the incidence, clinical course and identify risk factors for AIP.. A retrospective study including all IBD patients on AZA between January 2013 and July 2020 was conducted. Patients with AIP were considered.. Azathioprine-induced pancreatitis occurred in 33 patients (7.5%; 442 patients on AZA). The mean time receiving AZA until AIP was 25 days, with a mean dose of 88 mg. All patients had a mild course of disease, which resolved with suspension of AZA and with no complications. Smoking (P = 0.02), single daily dose of AZA (P < 0.001), and concomitant budesonide (P = 0.001) were risk factors for AIP. In multivariate analysis, concomitant treatment with budesonide (odds ratio, 5.3; P = 0.002) and single daily dose of AZA (odds ratio, 3.8; P = 0.002) were the only predictors of AIP.. Although AIP was a relatively common adverse effect, it presented a mild course in all patients. Smoking, concomitant use of budesonide, and single-dose regimen of AZA should be avoided in IBD patients treated with AZA.

Topics: Azathioprine; Budesonide; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Pancreatitis; Retrospective Studies

Microscopic colitis is an inflammatory bowel disease divided into two subtypes: collagenous colitis and lymphocytic colitis. With an increasing incidence of microscopic colitis exceeding those of ulcerative and Crohn's disease among elderly people in some countries, microscopic colitis is a debilitating life experience. Therefore, physicians should be familiar with its clinical features and management strategies because the disease deserves the same attention as the classical inflammatory bowel diseases. Here, state-of-the-art knowledge of microscopic colitis is provided from a global perspective with reference to etiopathology and how to establish the diagnosis with the overall aim to create awareness and improve rational management in clinical practice. The immune system and a dysregulated immune response seem to play a key role combined with risk factors (e.g. cigarette smoking) in genetically predisposed individuals. The symptoms are characterized by recurrent or chronic nonbloody, watery diarrhea, urgency, weight loss, and a female preponderance. As biomarkers are absent, the diagnosis relies on colonoscopy with a histological assessment of biopsy specimens from all parts of the colon. Although the disease is not associated with a risk of colorectal cancer, a recent nationwide, population-based cohort study found an increased risk of lymphoma and lung cancer. Budesonide is the first-line therapy for management, whereas immunomodulatory drugs (including biologics) and drugs with antidiarrheal properties may be indicated in those failing, dependent, or intolerant to budesonide. In microscopic colitis induced by checkpoint inhibitors, a drug class used increasingly for a wide range of malignancies, a more aggressive therapeutic approach with biologics introduced early seems reasonable. However, particular attention needs to be drawn to the existence of incomplete forms of microscopic colitis with the risk of being overlooked in routine clinical settings.

Topics: Aged; Biological Products; Budesonide; Cohort Studies; Colitis, Lymphocytic; Colitis, Microscopic; Female; Humans; Inflammatory Bowel Diseases

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

Topics: Administration, Oral; Adrenal Cortex Hormones; Biomarkers; Budesonide; C-Reactive Protein; Feces; Humans; Inappropriate Prescribing; Induction Chemotherapy; Inflammatory Bowel Diseases; Leukocyte L1 Antigen Complex; Magnetic Resonance Imaging; Medication Errors; Patient Education as Topic; Precision Medicine; Prednisolone; Time Factors

The pathophysiology of the inflammatory bowel disease collagenous colitis (CC) is poorly described. Our aim was to use RNA sequencing of mucosal samples from patients with active CC, CC in remission, refractory CC, ulcerative colitis (UC), and control subjects to gain insight into CC pathophysiology, identify genetic signatures linked to CC, and uncover potentially druggable disease pathways.. We performed whole transcriptome sequencing of CC samples from patients before and during treatment with the corticosteroid drug budesonide, CC steroid-refractory patients, UC patients, and healthy control subjects (n = 9-13). Bulk mucosa and laser-captured microdissected intestinal epithelial cell (IEC) gene expression were analyzed by gene set enrichment and gene set variation analyses to identify significant pathways and cells, respectively, altered in CC. Leading genes and cells were validated using reverse-transcription quantitative polymerase chain reaction or immunohistochemistry.. We identified an activation of the adaptive immune response to bacteria and viruses in active CC that could be mediated by dendritic cells. Moreover, IECs display hyperproliferation and increased antigen presentation in active CC. Further analysis revealed that genes related to the immune response (DUOX2, PLA2G2A, CXCL9), DNA transcription (CTR9), protein processing (JOSD1, URI1), and ion transport (SLC9A3) remained dysregulated even after budesonide-induced remission. Budesonide-refractory CC patients fail to restore normal gene expression, and displayed a transcriptomic profile close to UC.. Our study confirmed the implication of innate and adaptive immune responses in CC, governed by IECs and dendritic cells, respectively, and identified ongoing epithelial damage. Refractory CC could share pathomechanisms with UC.

Topics: Adolescent; Adult; Aged; Budesonide; Cell Proliferation; Colitis, Collagenous; Colitis, Ulcerative; Collagen; Enterocytes; Extracellular Matrix; Female; Gene Expression Profiling; Gene Expression Regulation; Humans; Immunity; Inflammatory Bowel Diseases; Intestinal Mucosa; Male; Middle Aged; Stromal Cells; Transcription, Genetic; Young Adult

Inflammatory bowel disease (IBD) affects a confined area of the intestine and, therefore, administration of drugs via oral route is preferable. However, obstacles such as changes in the pH along gastrointestinal tract (GIT), enzymatic activity, and intraluminal pressure may cause low drug availability in the target tissue when delivered orally. Previous studies have pointed out the benefits of using micron-sized particles for targeting inflamed intestinal mucosa and nanoparticles for delivery of anti-inflammatory agents to the affected epithelial cells. We hypothesized that by combining the benefits of micro- and nano- particles, we could create a more efficient delivery system for budesonide, a glucocorticosteroid commonly used for anti-inflammatory IBD therapy. The aim of this study was to develop a novel multistage system for oral delivery designed to increase concentrations budesonidein the inflamed intestinal tissue. The multistage system consists of Stage 1 mesoporous silicon microparticles (S1MP) loaded with stage 2 poly-lactic-glycolic acid (PLGA) budesonide-encapsulating nanoparticles (BNP). BNP were efficiently loaded into S1MP (loading efficiency of 45.9 ± 14.8%) due to the large pore volume and high surface area of S1MP and exhibited controlled release profiles with enhanced drug dissolution rate in biologically relevant pHs. Due to the robustness in acidic pH and their geometry, S1MP protected the loaded budesonide in the acidic (gastric) pH with only 20% release. This allowed for the prolonged release of the BNP in the higher pH conditions (intestinal pH). The sustained release of BNP could facilitate accumulation in the inflamed tissue, enabling BNP to penetrate inflamed mucosa and release active budesonide to the target site. The multistage systems of S1MP and BNP were further evaluated in three-dimensional (3D) in vitro model of IBD and were found to (1) increase accumulation of BNP in the inflamed areas, (2) restore the barrier function of Caco-2 inflamed monolayer, and (3) significantly reduce pro-inflammatory cytokine release almost to the level of the healthy control.

Topics: Anti-Inflammatory Agents; Budesonide; Caco-2 Cells; Cell Line, Tumor; Delayed-Action Preparations; Drug Carriers; Drug Delivery Systems; Drug Liberation; Humans; Hydrogen-Ion Concentration; Inflammation; Inflammatory Bowel Diseases; Intestinal Mucosa; Nanoparticles; Particle Size; Polylactic Acid-Polyglycolic Acid Copolymer; Silicon; Solubility

For site-specific drug delivery in inflammatory bowel disease, reducible sodium alginate nanoparticles cross-linked with disulfide linkage were developed. Nanoparticles were synthesized in deionized water through self-assembly of amphiphilic thiolated sodium alginate Alg-Cys and subsequently produced cross-linking of disulfide bonds. TEM image showed a spherical core-shell configuration with a size of about 430 nm for the nanoparticles. Dynamic light scattering (DLS) showed high stability, narrow size distribution, and pH-dependent swelling transition for the nanoparticles. Cytotoxicity study showed that there was no evident cell inhibition among the nanoparticles. Also, the size of the nanoparticles increased in 10 mM glutathione (GSH) solution due to the cleavage of disulfides within their network structures. Compared to that in GSH-free buffer, there was a remarkable increase in drug release in pH 7.4 buffer with GSH from drug-loaded nanoparticles, indicating that the nanoparticles could be used for colon-specific drug delivery.

Topics: Alginates; Budesonide; Drug Carriers; Drug Delivery Systems; Drug Liberation; Humans; Inflammatory Bowel Diseases; Nanoparticles

A self-assembled and oxidation-degradable Janus-prodrug, termed as Bud-ATK-Tem (B-ATK-T), was fabricated by ROS-responsive aromatized thioketal (ATK) linked anti-inflammatory drug budesonide (Bud) and antioxidant tempol (Tem). Benefiting from the hydrophobic interactions and π-π stacking interactions of ATK, prodrug B-ATK-T could self-assemble into nanoparticles (NP) in water containing lecithin and DSPE-PEG

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Budesonide; Cyclic N-Oxides; Disease Models, Animal; Drug Delivery Systems; Drug Liberation; Inflammation; Inflammatory Bowel Diseases; Macrophages; Male; Mice; Mice, Inbred C57BL; Nanoparticles; Prodrugs; RAW 264.7 Cells; Reactive Oxygen Species; Spin Labels

Topics: Anti-Inflammatory Agents; Budesonide; Dermatologic Agents; Humans; Inflammatory Bowel Diseases; Male; Mesalamine; Middle Aged; Rosacea

The major challenge involved in the treatment of inflammatory bowel disease is targeted delivery of the drug at the site of inflammation. As nanoparticles possess the ability to accumulate at the site of inflammation, present investigation aims at development of Budesonide-loaded nanostructured lipid carrier systems (BDS-NLCs) for the treatment of inflammatory bowel disease. BDS-NLCs were prepared by employing a high pressure homogenization technique. Various preliminary trials were performed for optimization of the NLCs in which different processes, as well as formulation parameters, were studied. The BDS-NLCs was optimized statistically by applying a 3-factor/3-level Box-Behnken design. Drug concentration, surfactant concentration, and emulsifier concentration were selected as independent variables, and % entrapment efficiency and particle size were selected as dependent variables. The best batch comprises of 10%, 7%, and 20% w/w concentration of drug, surfactant, and emulsifier, respectively, with % entrapment efficiency of 92.66 ± 3.42% and particle size of 284.0 ± 4.53 nm. Further, in order to achieve effective delivery of nanoparticulate system to colonic region, the developed BDS-NLCs were encapsulated in Eudragit

Topics: Budesonide; Chemistry, Pharmaceutical; Drug Carriers; Drug Delivery Systems; Drug Implants; Drug Liberation; Inflammatory Bowel Diseases; Lipids; Nanoparticles; Nanostructures; Particle Size

The purpose of this study was to develop an oral nanocarrier as budesonide delivery system and to evaluate its therapeutic potential for inflammatory bowel disease (IBD). The nanoparticles (NPs) based on an amphiphilic inulin polymer with 4-aminothiophenol (ATP) grafted onto carboxymethyl inulin (CMI) were prepared. The particle sizes were about 210.18 nm and had the obvious pH/redox sensitive swelling transitions. The drug-release study of NPs <-- >in vitro showed a low release rate (about 45 wt%) in GSH-free media, whereas high release rate (about 80 wt%) in the media containing 20 mM GSH, exhibiting a redox-responsive property. Further in vivo experiments found the NPs tended to accumulate in inflamed sites, and exerted excellent therapeutic efficacy in comparison to drug suspension in colitis mice model. All the results demonstrated that the redox-sensitive NPs, based on amphiphilic inulin, may be used as colon-targeted drug delivery for the treatment of IBD.

Topics: Aniline Compounds; Budesonide; Drug Delivery Systems; Inflammatory Bowel Diseases; Inulin; Nanoparticles; Oxidation-Reduction; Sulfhydryl Compounds

The major challenge for the treatment of inflammatory bowel disease (IBD) is the incompetence to deliver the drug molecule selectively at the site of inflammation. Taking this into consideration, we proposed development of mannosylated nanostructured lipid carrier system (Mn-NLCs) for active targeting and site-specific delivery of budesonide to the inflamed tissues. The developed Mn-NLCs were characterized for particle size and size distribution, zeta potential, %entrapment efficiency, FTIR and TEM analysis. Furthermore, to ensure delivery of developed cargo to the colonic region, the Mn-NLCs were encapsulated using Eudragit

Topics: Body Weight; Budesonide; Cell Line; Cell Survival; Colon; Drug Carriers; Drug Liberation; Engineering; Humans; Inflammatory Bowel Diseases; Kinetics; Lipids; Mannose; Nanoparticles; Organ Size; Surface Properties

Inflammatory bowel disease (IBD) is a chronic inflammatory gastrointestinal disorder that affects more than 1 million individuals in the USA. Local therapy with enema formulations, such as micronized budesonide (Entocort

Topics: Animals; Anti-Inflammatory Agents; Budesonide; Colon; Drug Compounding; Drug Delivery Systems; Enema; Inflammatory Bowel Diseases; Male; Mice; Mice, Inbred C57BL; Mucus; Nanoparticles; Poloxamer; Polystyrenes; Suspensions; Trinitrobenzenesulfonic Acid

Orally administrable drug delivery vehicles are developed to manage incurable inflammatory bowel disease (IBD), however, their therapeutic outcomes are compromised by the side effects of systemic drug exposure. Herein, we use hyaluronic acid functionalized porous silicon nanoparticle to bridge enzyme-responsive hydrogel and pH-responsive polymer, generating a hierarchical structured (nano-in-nano-in-micro) vehicle with programmed properties to fully and sequentially overcome the multiple obstacles for efficiently delivering drugs locally to inflamed sites of intestine. After oral administration, the pH-responsive matrix protects the embedded hybrid nanoparticles containing drug loaded hydrogels against the spatially variable physiological environments of the gastrointestinal tract until they reach the inflamed sites of intestine, preventing premature drug release. The negatively charged hybrid nanoparticles selectively target the inflamed sites of intestine, and gradually release drug in response to the microenvironment of inflamed intestine. Overall, the developed hierarchical structured and programmed vehicles load, protect, transport and release drugs locally to inflamed sites of intestine, contributing to superior therapeutic outcomes. Such strategy could also inspire the development of numerous hierarchical structured vehicles by other porous nanoparticles and stimuli-responsive materials for the local delivery of various drugs to treat plenty of inflammatory gastrointestinal diseases, including IBD, gastrointestinal cancers and viral infections.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Budesonide; Cell Line; Delayed-Action Preparations; Drug Delivery Systems; Humans; Hyaluronic Acid; Hydrogen-Ion Concentration; Inflammatory Bowel Diseases; Intestines; Male; Mice, Inbred C57BL; Nanoparticles; Polymers; Porosity; Silicon

Maintaining disease remission throughout pregnancy in women with inflammatory bowel disease is of the utmost importance to decrease the risk of adverse outcome. In general, corticosteroids are safe to use during pregnancy, but no data exist in the specific use of budesonide MMX. We report four cases of budesonide MMX in pregnancy and pregnancy outcome.. Four women with inflammatory bowel disease experienced disease activity during pregnancy. They were treated with budesonide MMX in an attempt to obtain clinical remission. Disease activity was assessed through physician's global assessment as well as lower endoscopy.. Budesonide MMX proved effective in achieving remission in three out of four women. One woman had an uncomplicated colectomy in the second trimester. All children were born normal for gestational age, with no congenital abnormalities and have reached all their developmental milestones. The four children have received vaccines according to the national immunization program without complications.. No adverse pregnancy outcomes were reported after the use of budesonide MMX. To our knowledge, this is the first report on the safety of budesonide MMX treatment in pregnant women with inflammatory bowel disease.

Topics: Administration, Oral; Adult; Anti-Inflammatory Agents; Budesonide; Colectomy; Female; Humans; Infant, Newborn; Inflammatory Bowel Diseases; Male; Pregnancy; Pregnancy Outcome; Remission Induction; Severity of Illness Index; Young Adult

The purpose of this study was to evaluate the specifically targeted efficiency of budesonide loaded PLGA nanoparticles for the treatment of inflammatory bowel disease (IBD).. The nanoparticles were prepared by an oil/water (O/W) emulsion evaporation technique. The nanoparticles were characterized for their size, shape and in vitro drug release profile. Solid state characterization was carried out by differential scanning calorimetry (DSC) and X-ray Power diffraction (XPRD). In order to evaluate the targeted efficiency of nanoparticles, a particle localization study in the healthy and in the inflamed colon was determined in vivo. These data were complemented by cryo-sections.. Nanoparticles were 200 ± 05 nm in size with a smooth and spherical shape. The encapsulation efficiency was around 85 ± 3.5%, which was find-out by both, direct and indirect methods. Release of budesonide from the nanoparticles showed a biphasic release profile with an initial burst followed by sustained release. XPRD data revealed that the drug in the polymer matrix existed in crystalline state. Nanoparticles accumulation in inflamed tissues was evaluated by in-vivo imaging system and it was found that particles are accumulated in abundance at the site of inflammation when compared to the healthy group.. The study demonstrates that the budesonide loaded PLGA nanoparticles are an efficient delivery system for targeted drug delivery to the inflamed intestinal mucosa.

Topics: Animals; Anti-Inflammatory Agents; Budesonide; Colitis; Drug Carriers; Drug Delivery Systems; Drug Liberation; Humans; Inflammatory Bowel Diseases; Intestinal Absorption; Intestinal Mucosa; Lactic Acid; Mice, Inbred BALB C; Nanoparticles; Optical Imaging; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; X-Ray Diffraction

Topics: Azathioprine; Biological Products; Budesonide; Cell Adhesion Molecules; Drug Therapy, Combination; Humans; Inflammatory Bowel Diseases; Mesalamine; Tumor Necrosis Factor-alpha

Ulcerative colitis (UC) and Crohn's disease (CD) are diseases affecting the gastrointestinal tract. Treatment depends on the severity of the disease, site of inflammation, and patient's response. The aim of this study was to develop a zero-order sustained-release tablet containing both the anti-inflammatory drugs mesalazine and budesonide as a new treatment option for ileo-colonic CD and UC. Tablets were attained by wet granulation with hydroxypropyl methylcellulose and direct compression. Our newly developed tablet core was coated with different ColoPulse® coating thicknesses and the mesalazine and budesonide release profiles were investigated in a 600-min gastrointestinal simulation system (GISS) experiment, together with commercially available MMX®-mesalazine and MMX®-budesonide. Lag-time, release rate (k0), completeness of release, and zero-order correlation coefficient (R(2)0) could be manipulated by varying ColoPulse® coating thickness. Our newly developed combination preparation (C[4.92]) complied with all conducted European Pharmacopoeia tests as well as an accelerated 6-month stability test and had a lag-time of 250min (simulated ileum targeted), a linear release profile (mesalazine R(2)0=0.9002; budesonide R(2)0=0.9481), and drug release of 100% mesalazine and 77% budesonide. Like C[4.92], MMX®-mesalazine had a linear (R(2)0=0.9883) and complete release profile (96%). However, C[4.92] lag-time was longer (250 vs. 210min), assuring simulated ileum specificity. Remarkably, MMX®-budesonide lag-time was 480min and release was only 7% with a linear character (R(2)0=0.9906). The in vitro results suggest that MMX®-budesonide effectiveness may be improved if budesonide release in the aqueous phase would be increased and that C[4.92] is a potential, new treatment option for ileo-colonic CD and UC.

Topics: Budesonide; Delayed-Action Preparations; Humans; Inflammatory Bowel Diseases; Mesalamine; Tablets

Glucocorticoids are widely used for the management of inflammatory bowel disease, albeit with known limitations for long-term use and relevant adverse effects. In turn, they have harmful effects in experimental colitis. We aimed to explore the mechanism and possible implications of this phenomenon. Regular and microbiota depleted C57BL/6 mice were exposed to dextran sulfate sodium (DSS) to induce colitis and treated with budesonide. Colonic inflammation and animal status were compared. In vitro epithelial models of wound healing were used to confirm the effects of glucocorticoids. Budesonide was also tested in lymphocyte transfer colitis. Budesonide (1-60μg/day) exerted substantial colonic antiinflammatory effects in DSS colitis. At the same time, it aggravated body weight loss, increased rectal bleeding, and induced general deterioration of animal status, bacterial translocation and endotoxemia. As a result, there was an associated increase in parameters of sepsis, such as plasma NOx, IL-1β, IL-6, lung myeloperoxidase and iNOS, as well as significant hypothermia. Budesonide also enhanced DSS induced colonic damage in microbiota depleted mice. These effects were correlated with antiproliferative effects at the epithelial level, which are expected to impair wound healing. In contrast, budesonide had significant but greatly diminished deleterious effects in noncolitic mice or in mice with lymphocyte transfer colitis. We conclude that budesonide weakens mucosal barrier function by interfering with epithelial dynamics and dampening the immune response in the context of significant mucosal injury, causing sepsis. This may be a contributing factor, at least in part, limiting clinical usefulness of corticoids in inflammatory bowel disease.

Topics: Animals; Anti-Inflammatory Agents; Bacterial Translocation; Biomarkers; Budesonide; Colon; Dextran Sulfate; Disease Models, Animal; Dose-Response Relationship, Drug; Dysbiosis; Endotoxemia; Female; Gastrointestinal Agents; Gastrointestinal Hemorrhage; Glucocorticoids; Homeodomain Proteins; Inflammatory Bowel Diseases; Intestinal Mucosa; Mice, Inbred C57BL; Mice, Knockout; Specific Pathogen-Free Organisms; Weight Loss

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

Topics: Administration, Topical; Anti-Inflammatory Agents; Budesonide; Humans; Inflammatory Bowel Diseases

The purpose of this study was to investigate the therapeutic potential of budesonide loaded nanocarriers for the treatment of inflammatory bowel disease (IBD). First, budesonide was encapsulated in poly(lactic-co-glycolic) acid (PLGA) nanoparticles by an oil in water (O/W) emulsion technique. A second batch of the same nanoparticles was additionally coated with a pH-sensitive methyl-methacrylate-copolymer. The particle sizes of the plain and the coated PLGA were 200±10.1nm and ~240±14.7nm, respectively. As could be shown in vitro, the pH-sensitive coating prevented premature drug release at acidic pH and only releases the drug at neutral to slightly alkaline pH. The efficacy of both coated and plain nanoparticle formulations was assessed in different acute and chronic colitis mouse models, also in comparison to an aqueous solution of the drug. The dose was always the same (0.168mg/kg). It was found that delivery by coated PLGA nanoparticles alleviated the induced colitis significantly better than by plain PLGA particles, which was already more effective than treatment with the same dose of the free drug. These data further corroborate the potential of polymeric nanocarriers for targeted drug delivery to the inflamed intestinal mucosa, and that this concept can still be further improved regarding the oral route of administration by implementing pH-dependent drug release characteristics.

Topics: Animals; Anti-Inflammatory Agents; Budesonide; Cytokines; Disease Models, Animal; Drug Carriers; Drug Compounding; Drug Liberation; Hydrogen-Ion Concentration; Inflammatory Bowel Diseases; Intestinal Mucosa; Lactic Acid; Methylmethacrylate; Mice, Inbred BALB C; Nanoparticles; Particle Size; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Surface Properties

Local delivery to bowel tissue through oral administration is a challenging but a desirable goal to treat diseases like inflammatory bowel disease (IBD). Colon specific drug delivery system should be capable of protecting the drug en route colon.. Liposomes have shown potential to specific accumulation at inflammation site thus reduce toxicity; hence it can be used for effective treatment of IBD.. Liposomes prepared using thin film hydration method. Statistical design was used for optimization. Colitis was induced using acetic acid. Inverted sac method was used as ex vivo model for IBD. Myeloperoxidase (MPO) activity and histopathology comparative study was carried out. Liposomes were formulated in enteric coated capsules to deliver the liposome specifically in initial segment of colon.. Particle size and entrapment efficiency were between 200 and 300 nm and 40 and 60%, respectively. In vivo and ex vivo study indicates higher accumulation of liposomes in colonic region as compared to pure drug. Enteric coated capsules delivered the drug after 5 h lag time.. Low particle size is attributed to low lipid content and stabilization due to surfactant. At higher cholesterol level, vesicles cannot reshuffle into smaller vesicles due to rigidization. Study shows higher accumulation of liposomes due to its lipoidal nature as compared to pure drug due to membrane transfer mechanism of drug thus MPO significantly lowers as compared to standard group (p < 0.05).. Higher accumulation of liposomal drug in inflammatory area and specific release of liposomes by enteric coated capsules provide better option for the treatment of colonic disease.

Topics: Animals; Anti-Inflammatory Agents; Budesonide; Calorimetry, Differential Scanning; Colon; Disease Models, Animal; Drug Carriers; Drug Compounding; Drug Design; Drug Stability; Inflammatory Bowel Diseases; Liposomes; Male; Microscopy, Electron, Scanning; Particle Size; Peroxidase; Rats; Rats, Wistar; Solubility; Spectroscopy, Fourier Transform Infrared; Surface Properties

Although acute dextran sodium sulphate (DSS)-induced colitis in mice is frequently used as a preclinical model for testing drugs involved in inflammatory bowel disease (IBD), only limited data is available that compares the efficacy of established drug treatments and combinations employed in IBD. We have therefore compared the efficacy of aminosalicylates (mesalazine, olsalazine), corticosteroids (budesonide), thiopurines (6-thioguanine (6-TG)) and cyclosporine A (CsA) and combinations thereof as well as the EP4 agonist AGN205203 in the acute DSS-colitis model.. Female BALB/c mice were challenged with 4% DSS in drinking water for 7 days to induce colitis and treated daily with different drugs/combinations orally. Disease scores (diarrhoea, bleeding, disease activity index), systemic (body weight loss, serum amyloid A levels) and colonic (myeloperoxidase activity, length and histopathology) inflammation parameters were analysed.. Mesalazine, olsalazine (100mg/kg) and budesonide (0.5mg/kg) were only weakly active or even worsened colitis. 6-TG dose-dependently reduced systemic and colonic inflammation parameters with estimated ED50 values between 0.5-4 mg/kg. CsA (10, 25 and 50mg/kg) dose-dependently reduced colitis with high efficacy on systemic inflammation. A combination of CsA 25mg/kg+olsalazine 100mg/kg produced a more pronounced anti-inflammatory effect than the compounds given alone. AGN205203 (3, 10 and 30 mg/kg BID) was the most efficacious compound and almost completely inhibited colitis.. 6-TG and CsA are suitable reference compounds in the DSS mouse model. CsA+olsalazine, as a combination, was more efficacious than the compounds given alone, supporting combination treatments in IBD.

Topics: Aminosalicylic Acids; Animals; Anti-Inflammatory Agents; Budesonide; Colitis; Colon; Cyclosporine; Dextran Sulfate; Drug Therapy, Combination; Female; Gastrointestinal Agents; Humans; Inflammatory Bowel Diseases; Mesalamine; Mice; Mice, Inbred BALB C; Receptors, Prostaglandin E, EP4 Subtype; Thioguanine

Drug formulation screenings for treatment of inflammatory bowel disease (IBD) are mostly conducted in chemically induced rodent models that represent acute injury-caused inflammation instead of a chronic condition. To accurately screen drug formulations for chronic IBD, a relevant model that mimics the chronic condition in vitro is urgently needed. In an effort to reduce and potentially replace this scientifically and ethically questionable animal testing for IBD drugs, our laboratory has developed an in vitro model for the inflamed intestinal mucosa observed in chronic IBD, which allows high-throughput screening of anti-inflammatory drugs and their formulations. The in vitro model consists of intestinal epithelial cells, human blood-derived macrophages, and dendritic cells that are stimulated by the inflammatory cytokine interleukin-1β. In this study, the model was utilized for evaluation of the efficacy and deposition of budesonide, an anti-inflammatory drug, in three different pharmaceutical formulations: (1) a free drug solution, (2) encapsulated into PLGA nanoparticles, and (3) encapsulated into liposomes. The in vitro model of the inflamed intestinal mucosa demonstrated its ability to differentiate therapeutic efficacy among the formulations while maintaining the convenience of conventional in vitro studies and adequately representing the complex pathophysiological changes observed in vivo.

Topics: Animal Testing Alternatives; Anti-Inflammatory Agents; Budesonide; Caco-2 Cells; Cells, Cultured; Coculture Techniques; Dendritic Cells; Humans; Inflammatory Bowel Diseases; Interleukin-1beta; Interleukin-8; Lactic Acid; Liposomes; Macrophages; Microscopy, Confocal; Nanoparticles; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer

Novel pH-sensitive nanospheres designed for colon-specific delivery were prepared using polymeric mixtures of poly (lactic-co-glycolic) acid (PLGA) and a pH-sensitive methacrylate copolymer. Budesonide (BSD), a topically active corticosteroid, was entrapped as a model drug. The therapeutic efficacy of the prepared nanospheres was assessed using the trinitrobenzenesulfonic acid (TNBS) colitis rat model, in comparison with conventional enteric microparticles. In addition, the colon targeting properties, systemic bioavailability, and specific uptake by the inflamed colon mucosa were evaluated using coumarin-6 (C-6)-loaded nanospheres. The prepared nanospheres showed strongly pH-dependent drug release properties in acidic and neutral pH values followed by a sustained release phase at pH 7.4. Animal experiments revealed the superior therapeutic efficiency of BSD-loaded nanospheres in alleviating the conditions of TNBS-induced colitis model. The in vivo studies using C-6-loaded nanospheres displayed higher colon levels and lower systemic availability of the fluorescent marker when compared with simple enteric coating. Moreover, quantitative analysis of the fluorescent marker and confocal laser scanning studies showed strong and specific adhesion of the nanospheres to the ulcerated and inflamed mucosal tissue of the rat colon. In conclusion, the proposed nanosphere system combined the properties of pH-sensitivity, controlled release, and particulate targeting that could be useful for colon-specific delivery in inflammatory bowel disease.

Topics: Animals; Budesonide; Colitis; Colon; Disease Models, Animal; Drug Carriers; Drug Delivery Systems; Hydrogen-Ion Concentration; Inflammatory Bowel Diseases; Nanospheres; Nanotechnology; Polymers; Rats; Tablets, Enteric-Coated; Trinitrobenzenesulfonic Acid

Among 34 children diagnosed to have inflammatory bowel disease (IBD) over past 8 years, 23 had Crohns disease and 11 had ulcerative colitis. Pediatric patients accounted for 7% of new cases of IBD seen annually. Median delay in diagnosis was 15 months. Nutritional impairment was significantly more common in Crohns disease.

Topics: Adolescent; Anti-Inflammatory Agents; Antineoplastic Agents; Azathioprine; Budesonide; Catchment Area, Health; Child; Child, Preschool; Drug Combinations; Drug Therapy, Combination; Female; Humans; India; Infant; Inflammatory Bowel Diseases; Male; Methotrexate; Prednisolone; Prevalence

Delayed release budesonide was approved by the FDA for the treatment of mildly to moderately active Crohn's disease involving the ileum and ascending colon. Controlled trials have demonstrated that budesonide is effective in inducing remission and for maintenance of remission, with less frequent steroid side effects than conventional steroids. We sought to determine the benefit of this medication in clinical practice and to identify any non-FDA-approved uses that may warrant further study.. Patients in whom oral budesonide was prescribed between November 1, 2001 and October 31, 2002, were identified and medical records were reviewed. Patients were categorized by indication for therapy: ileocolonic Crohn's disease (group 1), Crohn's disease elsewhere (group 2), and other conditions (group 3).. A total of 225 patients were identified (108 in group 1, 62 in group 2, and 55 in group 3). Group 3 included patients with microscopic colitis (n = 28), pouchitis (n = 13), ulcerative colitis (n = 12), and celiac disease (n = 2). A favorable outcome occurred in 61% of group 1 patients but only 24% of patients in group 2. In group 3, only microscopic colitis patients and pouchitis patients experienced response rates >50% (77% and 60%, respectively).. Budesonide is effective in a majority of patients with ileocolonic Crohn's disease and microscopic colitis, which is consistent with results reported from clinical trials. A majority of patients with pouchitis also benefit from budesonide therapy, but prospective controlled trials are necessary to clarify the benefit in this group.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Budesonide; Female; Humans; Inflammatory Bowel Diseases; Male; Middle Aged; Retrospective Studies; 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

TARGIT technology (West Pharmaceutical Services) is designed for site-specific delivery of drugs in the gastrointestinal (GI) tract and, in particular, targeted release into the colonic region. A key area of application is the delivery of therapeutic agents for local treatment of lower GI diseases. The technology is based on the application of pH-sensitive coatings onto injection-moulded starch capsules. An extensive body of clinical data has been generated showing reliable in vivo performance of the capsules. In gamma-scintigraphy studies around 90% of TARGIT capsules (n = 84) delivered their contents to the target site of the terminal ileum and colon. TARGIT-based products are in active clinical development for the treatment of conditions including inflammatory bowel diseases.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Budesonide; Capsules; Chemistry, Pharmaceutical; Colon; Drug Delivery Systems; Gastrointestinal Agents; Humans; Hydrogen-Ion Concentration; Inflammatory Bowel Diseases; Polymethacrylic Acids; Solubility; Starch; Time Factors

Topics: Administration, Oral; Anti-Inflammatory Agents; Biological Availability; Budesonide; Humans; Inflammatory Bowel Diseases; Intestinal Absorption; Intestinal Mucosa; Metabolic Clearance Rate; Treatment Outcome

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

Development of topically active glucocorticosteroids with minimal systemic effects is paramount in improving therapy in inflammatory bowel disease. Our experimental model in the rat has proved useful for assessing topical versus systemic anti-inflammatory potency of glucocorticosteroids on the inflamed gut.. Experiments were performed on allergen-sensitized perfused rat ileum in vivo. Mucosal exudation of plasma, induced by local allergen perfusion, was measured as the appearance of circulating 125I-labelled albumin in the gut lumen. Experiments compared the anti-exudative effects of oral budesonide (0.1 mg/kg) with oral prednisolone (1, 3.3 or 10 mg/kg) and saline, given by oral gavage 24 h prior to allergen challenge, and of topical budesonide (3 x 10(-5) mol/L) with saline, administered in the perfusate 4 h prior to allergen challenge. Systemic glucocorticosteroid activity was assessed by weighing thymus glands after sacrifice.. Allergen-induced plasma exudation was significantly reduced by oral budesonide, oral prednisolone (dose-dependently) and topically applied budesonide; topical budesonide was effective within 4 h. While prednisolone significantly reduced the relative thymus weight at both 3.3 and 10 mg/kg, budesonide given orally, 0.1 mg/kg, or topically, 3 x 10(-5) mol/L, had no significant effect.. Budesonide, administered orally or topically, shows higher selectivity for the gut mucosa than prednisolone and produces local anti-inflammatory responses comparable to prednisolone, without the accompanying systemic effects.

Topics: Administration, Oral; Administration, Topical; Animals; Anti-Inflammatory Agents; Budesonide; Disease Models, Animal; Drug Evaluation, Preclinical; Inflammatory Bowel Diseases; Intestinal Mucosa; Male; Ovalbumin; Prednisolone; Rats; Rats, Sprague-Dawley

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

Topics: Anti-Inflammatory Agents; Budesonide; Humans; Inflammatory Bowel Diseases

The past 12 months have been a period of steady progress in the field of gastroenterology. Helicobacter pylori continues to dominate many areas of clinical research and the indications for eradication are increasing. A potent, topically-acting corticosteroid for Crohn's disease, and new hope and potential treatments for IBS sufferers are other developments.

Topics: Administration, Topical; Anti-Inflammatory Agents; Budesonide; Colonic Diseases, Functional; Dietary Fiber; Gastrointestinal Neoplasms; Glucocorticoids; Helicobacter Infections; Humans; Inflammatory Bowel Diseases; Peptic Ulcer; Pregnenediones; Sigmoidoscopy