Oral budesonide in the treatment of patients with primary biliary cirrhosis with a suboptimal response to ursodeoxycholic acid
Open accessAbstract
Ursodeoxycholic acid (UDCA) is a safe and effective medical therapy for most patients with primary biliary cirrhosis (PBC). However, some patients show an incomplete response to UDCA therapy. Treatment with corticosteroids may be of benefit although at the expense of systemic side effects. Budesonide, a corticosteroid with an extensive first-pass hepatic metabolism appeared promising for the treatment of PBC. The aim of this study was to evaluate the safety and estimate the efficacy of budesonide in patients with PBC, who have shown a suboptimal response to UDCA. Twenty-two patients with PBC, 16 women, median age of 50 who had been on UDCA (13-15 mg/kg/d) for a mean of 46 months (range 6-108 months) and had shown a persistent elevation of alkaline phosphatase activity at least 2 times the upper limit of normal were enrolled. Oral budesonide, 9 mg daily was administered for 1 year and patients continued on the same dosage of UDCA. There was a significant, but transitory improvement in serum levels of total bilirubin (P = .001) and a significant, but marginal improvement in serum alkaline phsophatase (P = .001) with combination therapy. The Mayo risk score increased significantly (P = .02) and there was a significant loss of bone mass (P < .001) of the lumbar spine. Budesonide-induced hyperglycemia and cosmetic adverse effects were noted in 2 patients. In conclusion, oral budesonide appears to add minimal, if any, additional benefit to UDCA, and it is associated with a significant worsening of osteoporosis in patients with PBC.
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Doubling the dose of UDCA and adding colchicine, methotrexate, or silymarin have not been found to be of benefit over and beyond that achieved with UDCA alone.
“Doubling the dose of UDCA and adding colchicine, methotrexate, or silymarin have not been found to be of benefit over and beyond that achieved with UDCA alone.(163,178,179)”
From Primary Biliary Cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases (2019) · cites this paper as [179]
The Discussion (page not specified) says adding colchicine showed no benefit for patients with a suboptimal response to UDCA. It also reports negative results from larger controlled trials of methotrexate, while acknowledging biochemical improvement in a few selected patients. Our copy does not establish the claimed lack of benefit from doubling the UDCA dose or adding silymarin. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn a US open label study of 22 biochemical non-responders (ALP persistently >2 x ULN), only a very minimal additional benefit of budesonide to UDCA was reported, with a significant increase in the Mayo PBC score prognostic index and significant deterioration in bone mineral density.
“In a US open label study of 22 biochemical non-responders (ALP persistently >2 x ULN), only a very minimal additional benefit of budesonide to UDCA was reported, with a significant increase in the Mayo PBC score prognostic index and significant deterioration in bone mineral density; true comparison is challenging, however, because this cohort may have had patients at later stages of disease.161”
From The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines (2018) · cites this paper as [161]
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- Authors
- Angulo, P., Jorgensen, R. A., Keach, J. C., Dickson, R. E., Smith, C., & Lindor, K. D.
- Affiliations
- Mayo Clinic (US)
- Abbott Northwestern Hospital (US)
- Corresponding author
- Lindor, Keith D.
- Venue
- Hepatology
- Published
- 2000-02
- Volume
- 31
- Issue
- 2
- Pages
- 318-323
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W2084079239
- Cited by
- 179
- References
- 41
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 2 · 2022: 7 · 2021: 4 · 2020: 8 · 2019: 5 · 2018: 10 · 2017: 12 · 2016: 10 · 2015: 13 · 2014: 12 · 2013: 9 · 2012: 4
- FWCI
- 8.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1r03dk052344-01)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 52344)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- primary biliary cirrhosis, budesonide, ursodeoxycholic acid, corticosteroid therapy, combination therapy, alkaline phosphatase, total bilirubin, Mayo risk score, bone loss, osteoporosis, hyperglycemia, adverse effects
- MeSH terms
- Administration, Oral, Administration, Topical, Adult, Aged, Alkaline Phosphatase, Anti-Inflammatory Agents, Bilirubin, Cholagogues and Choleretics, Drug Therapy, Combination, Female, Glucocorticoids, Humans, Liver Cirrhosis, Biliary, Male, Middle Aged, Osteoporosis, Pilot Projects, Ursodeoxycholic Acid, Bone Density, Treatment Failure, Retreatment, Budesonide
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