Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oral chronic graft versus host disease (cGVHD) is common and a major cause of morbidity and loss of quality of life in long term survivors. Cyclosporine with prednisone remains the first line therapy for oral manifestations of cGVHD. However, even with routine administration of systemic agents, many patients with oral manifestations of cGVHD do not have resolution of their disease and may benefit from incorporation of local therapy. Budesonide is a highly potent steroid which has minimal systemic side effects and being used for oral cGVHD. We designed a retrospective study to compare treatment results of patients with oral cGVHD who received topical budesonide in addition to systemic therapy that consists of combined prednisone and cyclosporine (Group A, n = 12), with the treatment results of patients who were administered the same systemic therapy alone (Group B, n = 11) to determine whether budesonide mouthwash had any advantage on response rates. Three mg topical budesonide/10 ml saline was used 3-4 times a day for up to 6 months in group A. Diagnosis, clinical staging, and treatment response scoring for cGVHD were performed according to National Institutes of Health (NIH) consensus criteria. At the baseline examination, there were no statistically significant differences in terms of median oral cGVHD examination scores between two groups. After treatment, there was statistically significant decrease in median oral cGVHD examination scores compared to baseline (P < 0.001 and 0.021), and significant differences were found between two groups (P < 0.032). Overall response rate was 83% and 36% for group A and B, respectively (P = 0.036). However, no statistically significant differences were found between median pain scores of two groups before and after treatment (P = 0.740 and P = 0.091). No major systemic side effects and oral candidiasis were observed in two groups of patients. We concluded that topical budesonide might be added to systemic therapy to obtain better response rates in patients with oral cGHVD.
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PMID:The effect of budesonide mouthwash on oral chronic graft versus host disease. 1710 90

Budesonide (BUD) is a steroid with a low bioavailability, which has been used for the treatment of oral manifestations of chronic GVHD (cGVHD). We retrospectively evaluated the efficacy of BUD in the treatment of gastrointestinal cGVHD. Thirteen patients (median age 47 years) receiving BUD for the treatment of cGVHD after allogeneic hematopoietic SCT for hematological malignancies were evaluated for response. Five patients had isolated gastrointestinal cGVHD and 8 patients had mild multiorgan involvement including gastrointestinal manifestations. Six patients received CYA at the time of onset of cGVHD, which was continued during treatment with BUD. Treatment consisted of BUD, with an initial daily dose of 3 x 3 mg orally. Complete resolution of cGVHD was achieved in seven patients, and one patient achieved partial remission of cGVHD. One patient achieved complete resolution of gastrointestinal cGVHD, while systemic manifestations of cGVHD remained stable. Four patients progressed on BUD. Owing to the predominantly local effect, relapse of symptoms of cGVHD after withdrawal of immunosuppression (n=3) as well as progression of GVHD at other sites (n=3) has been observed. BUD represents a treatment option in mild-to-moderate cGVHD, which is well tolerated and associated with a high response rate in gastrointestinal cGVHD.
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PMID:Enteral budesonide in treatment for mild and moderate gastrointestinal chronic GVHD. 1864 80

Buccal administration of budesonide (mouthwash) may be effective as a topical add-on therapy in patients with oral chronic graft-versus-host disease (cGVHD). Safety of approved oral budesonide is based on high intestinal and hepatic extraction by cytochrome P450 3A (CYP3A) enzymes. The purpose of this study was to evaluate the presystemic extraction and pharmacodynamic action of buccal budesonide. Oral budesonide (3 mg) was taken as reference to which various single and multiple dose regimens of buccal budesonide were compared. Budesonide and the 2 main CYP3A-dependent metabolites (6beta-hydroxybudesonide, 16alpha-hydroxyprednisolone) were analyzed in blood and urine along with the drug's effect on endogenous cortisol in 12 healthy subjects and 7 patients with oral cGVHD. We assessed CYP3A-dependent metabolites in both healthy subjects and patients after buccal budesonide. Whereas systemic exposure to budesonide was markedly lower in healthy subjects after the mouthwash compared to oral dosing (mean relative bioavailability 18%-36%), the systemic concentrations thereafter in patients were as high as those after the identical dose of oral budesonide. Reduced buccal CYP3A activity (lower inactivation of budesonide) in patients contributed to this remarkable difference. Endogenous cortisol was suppressed in some patients during 1 week of continuous treatment with buccal budesonide (3 x 3 mg per day). We are the first to report the biotransformation of budesonide via CYP3A enzymes after buccal drug administration. Only 2% of a buccal dose of budesonide achieves systemic circulation in healthy individuals; that fraction is 10% in patients with oral cGVHD, probably because of alterations in drug uptake and metabolization.
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PMID:Pharmacokinetics and pharmacodynamic action of budesonide after buccal administration in healthy subjects and patients with oral chronic graft-versus-host disease. 1920 24

Graft versus host disease (GVHD) is an alloimmune inflammatory process, which results from a donor-origin cellular response against host tissues. The chronic syndrome of GVHD (cGVHD) occurs in approximately 50% of patients post hematopoietic stem cell transplantation (HSCT) and remains the leading cause of non-malignant mortality. Oral cavity is one of the most frequent sites involved in cGVHD, possibly only second to skin. The oral tissues targeted by cGVHD are the mucosae, the salivary glands, the musculoskeletal apparatus and the periodontal structures. The mucosal cGVHD is accompanied by pain and mucosal irritation. Patients with cGVHD present with mucosal erosion and atrophy, lichenoid-hyperkeratotic changes, pseudomembranous ulcerations and mucoceles. Dry mouth may exacerbate mucosal irritation and erosion. In addition to impaired oral functions, cGVHD may lead to secondary malignancies in the form of solid cancers, particularly squamous cell carcinomas of the oral cavity. Moreover, administration of systemic azathioprine, a commonly used immunosuppressive drug in cGVHD patients, may significantly increase the incidence of tumors of oral cavity. The increased risk of secondary malignancies indicates the need for lifelong surveillance, particularly in younger patients. Scoring of oral GVHD was first addressed by NIH only in 2005. The NIH consensus paper referred to standard criteria for diagnosis, classification, and response to treatment. These scales were introduced for clinical use, although they require prospective validation studies. In the past, other scales were suggested and may still be used for research purposes. Management of oral cGVHD is compromised of preventive protocols and when cGVHD is developed, systemic and topical treatment. Because the majority of patients with oral cGVHD will develop the extensive form of the disease, they will be treated systemically. Systemic treatment is based on steroids and immunosuppressants, and, thus, increases the frequency of opportunistic infections. Only a few well-designed controlled trials using systemic treatments for cGVHD assessed oral outcomes. When the oral mucosa is the only site resistant to high doses of systemic corticosteroids or when GVHD is manifested only in the oral mucosa, the treatment approach should be topical therapy. Topical steroid preparations are the mainstay of local treatment. Budesonide is a novel steroid preparation that is being developed in the recent years for cGVHD. Its high topical anti-inflammatory activity together with low systemic bioavailability may provide enhanced treatment effects for local oral disease while sparing the host immunity. Second line of topical therapy includes pharmacologic immunosuppressants and phototherapy, combined with palliative treatment. This article aims at presenting the novel information about the clinical presentation, scoring scales, long term complications and treatment for mucosal cGVHD.
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PMID:[Chronic graft-versus-host-disease involving the oral mucosa: clinical presentation and treatment]. 1926 64

Oral involvement is (very) common in chronic graft-versus-host disease and can cause discomfort and impairment of oral function. Budesonide, a highly potent corticosteroid with low systemic activity, can be used as a topical treatment for oral chronic graft-versus-host disease. We describe the development of a formulation of budesonide and sodium bicarbonate for use as mouthwash in patients with oral chronic graft-versus-host disease.
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PMID:Formulation of budesonide mouthwash for the treatment of oral chronic graft-versus-host disease. 2541 Dec 62