Immunomodulating Agents in Gastrointestinal Disease
Thomas F. Kresina in Immune Modulating Agents, 2020
Budesonide is an analogue of hydrocortisone initially used in an inhaled formulation for the treatment of asthma. In both oral and rectal forms, it suppresses inflammation in the bowel. However, because of extensive first-pass metabolism by the cytochrome P-450 enzymes in the liver, only 10% to 15% of absorbed budesonide has systemic bioavailabilty. The Canadian IBD study group found oral budesonide effective in inducing remission in 51% of patients with active CD receiving 9 mg of a slow-release form for 8 weeks compared with 20% of those receiving placebo [92], Budesonide was found to cause a dose-related reduction in basal and adrenocorticotropic hormone-(ACTH)-stimulated plasma cortisol concentration but was not associated with clinically important steroid side effects. Another study demonstrated that budesonide was almost as effective as prednisolone in treating active CD with fewer corticosteroid side effects and less suppression of pituitary adrenal function [93]. A recent Canadian study of budesonide in patients with CD in remission found that oral budesonide was well tolerated and prolonged remission compared to placebo [94]. However, there was no difference in remission rate compared to that of placebo at 1 year of follow-up.
Budesonide
Anton C. de Groot in Monographs in Contact Allergy, 2021
Budesonide is a 1:1 mixture of 2 diastereomers, the R and S diastereomers, which can both induce positive patch test reactions by themselves (99). Budesonide is available as inhalation powder and aerosol for the treatment of asthma, as nasal spray for allergic rhinitis and may also be administered orally or rectally for treating Crohn’s disease and colitis ulcerosa. It is the most commonly used corticosteroid molecule in liquid aerosols, but used in only a few countries for skin diseases in cream and ointment (e.g. Japan, Spain, Italy). Many case reports of contact allergic reactions to budesonide have been reported, mostly from nasal sprays (table 3.49.4) and from creams and ointments (table 3.49.6), and a lower number from inhalation sprays (table 3.49.5). Local allergic side effects of inhaled corticosteroids include stomatitis, perioral eczema, oropharyngeal pruritus, dryness, mouth erythema and edema, dry cough, dysphonia, dysphagia and odynophagia (pain when swallowing) (62,63,65). Symptoms often start early in the treatment (after several days) and may develop hours after inhalation (65).
Eosinophil Differentiation and Cytokine Networks in Allergic Inflammation
Gerald J. Gleich, A. Barry Kay in Eosinophils in Allergy and Inflammation, 2019
We have studied pharmacological regulation by corticosteroids in vitro of a number of these processes. Budesonide, a topical corticosteroid, in addition to diminishing nasal polyp size and cellular infiltrates of eosinophils and mast cells in vivo, inhibits gene expression and production of GM-CSF, IL-6, and IL-8 by nasal epithelial cells and fibroblasts (6,7,11,12). In a recent set of experiments, dose-dependent, direct inhibitory effects of budesonide on progenitors for basophils and eosinophils, using HL-60 cells after alkaline passage and butyrate induction or methylcellulose cultures, were observed (Fig. 2). These data are in agreement with information in the literature on the effects of steroids on eosinophil differentiation in vitro (3,4). An opposite effect of steroids on neutrophil differentiation is consistently found due to direct and indirect stimulatory effects on granulopoiesis, leading to neutrophil progenitor differentiation (13,14). GM-CSF production and gene expression are both influenced by steroids. Both up-regulation by IL-la and down-regulation by budesonide can be demonstrated in vitro (6,7,11,12). There may be several, interactive pharmacological effects of budesonide that eventuate in suppression or enhancement of inflammatory cell differentiation.
Real-world safety and efficacy of twice-daily budesonide 2-mg foam in patients with ulcerative colitis: interim analysis of post-marketing surveillance
Published in Expert Opinion on Pharmacotherapy, 2021
Teppei Omori, Masayuki Saruta, Akira Nagaki, Yuki Arai, Akira Ohta, Kiyotoshi Kuramoto, Yasuo Suzuki
For patients with distal colitis, topical drugs are generally considered more useful than oral drugs [2], as they yield quicker responses through direct actions of the drug with high concentrations at local inflammatory sites and fewer systemic adverse events (AEs), owing to its lower systemic bioavailability [8]. Currently, topical 5-aminosalicylic acid (5-ASA) is recommended as a first-line therapy for mild-to-moderate proctitis and left-sided colitis, and topical steroids are recommended as a second-line therapy for 5-ASA-refractory or -intolerant patients [9–11]. Topical steroids are effective in controlling acute colonic inflammation; however, their use is limited to short-term treatment, owing to the occurrence of systemic AEs after absorption through the rectal mucosa. Budesonide is a synthetic second-generation corticosteroid that has been used for the treatment of inflammatory bowel disease [12]. Moreover, budesonide is an antedrug characterized by low bioavailability with high first-pass degradation in the liver, thereby minimizing the occurrence of systemic AEs. The foam formulation of budesonide can be efficiently delivered from the rectum to the sigmoid colon by one-push dosing, covering the area for several hours [13]. This drug has been developed by Dr. Falk Pharma GmbH and was first approved in Europe in 2006, followed by the USA in 2014 [14,15]. As of July 2020, the drug was approved in 37 countries worldwide.
Investigational drug therapies for coeliac disease – where to from here?
Published in Expert Opinion on Investigational Drugs, 2018
James Haridy, Diana Lewis, Evan D. Newnham
Corticosteroids have traditionally been used in to induce remission in a number of immune-mediated diseases, including gastrointestinal disease such as Crohn’s, exerting anti-inflammatory and immunosuppressive effects via multiple pathways. Budesonide exerts marked a marked local anti-inflammatory effect whilst reducing systemic adverse effects due to extensive first-pass metabolism and minimal systemic bioavailability (10–15%) [75]. Although designed for IBD with predominant distal ileal and colonic delivery, up to 30% may be released in the proximal – mid small bowel [76]. A pilot study of 20 patients with newly diagnosed CD treated with 6 mg Budesonide in addition to a GFD revealed an increased bodyweight, general well-being score, and reduced stool weight compared with GFD alone over a 4-week treatment period [77]. Budesonide has been used more widely in refractory CD, with two further small trials displaying some efficacy in reducing the number of bowel movements without improvement seen in histological end points over 6–24 months [78,79]. Although encouraging, further studies are required with longer term safety data and novel formulations that permit more proximal small bowel release of Budesonide to be considered on a wider scale. A number of newer oral formulations including viscous or effervescent budesonide have been tested in eosinophilic oesophagitis and may be more applicable to CD-enteric coated formulations [80,81]. Outcomes from randomized controlled trials utilizing budesonide in newly diagnosed CD are awaited [82].
An update on the pharmacological management of autoimmune hepatitis
Published in Expert Opinion on Pharmacotherapy, 2021
Yooyun Chung, Mussarat N Rahim, Jonathon J Graham, Yoh Zen, Michael A Heneghan
Budesonide is metabolized in the liver via the first-pass system and should not be used in those with reduced hepatic clearance due to porto-systemic shunting (e.g. cirrhosis or portal vein thrombosis). Budesonide 9 mg daily in non-cirrhotic patients has been demonstrated to have comparable results to prednisolone with the benefit of fewer steroid induced side effects [15]. A randomized, double-blind study assigned patients to receive either budesonide 9 mg or prednisolone 40 mg (fixed weaning regimen) for 6 months with both arms receiving azathioprine 1–2 mg/kg. Patients in both arms with biochemical response at 3 months or after 6 months were enrolled in an open-label study to receive budesonide. Biochemical response was achieved in 60% of the budesonide group compared to 38.8% in the prednisolone group (p = 0.001). Overall, 72% of the patients in the budesonide group reported no corticosteroid-related side effects compared to 46.6% in the prednisone group (p = 0.001). This study showed lower remission rates in the prednisolone group when compared to previous studies which may reflect the fixed weaning regimen used in this study, as opposed to the tapering of prednisolone dosage according to response. In a more recent retrospective study, patients intolerant or dependent on prednisolone were switched to budesonide. Results demonstrated 67% of the patients with biochemical response at 24 months. In addition, bone mineral density remained stable or improved in 14/15 patients at 24 months [16]. Budesonide can be considered unequivocally in those at high risk of side effects with prednisolone [17].
Related Knowledge Centers
- Medication
- Corticosteroid
- Metered-Dose Inhaler
- Nasal Spray
- Asthma
- Chronic Obstructive Pulmonary Disease
- Allergic Rhinitis
- Nasal Polyp
- Inflammatory Bowel Disease
- Crohn's Disease