Biochemical and Histological Effectiveness of Long-term Use of Fenofibrate for Asymptomatic Primary Biliary Cholangitis

Dohmen, Kazufumi; Tanaka, Hirofumi; Haruno, Masatora; Aishima, Shinichi

doi:10.17554/j.issn.2224-3992.2016.05.635

Cited by 5 publications

(5 citation statements)

References 41 publications

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“…As shown in our analysis, four PPAR agonists were more effective than other drugs in reducing ALP biochemical levels as adjunctive therapy for patients with PBC refractory to UDCA, bezafibrate and fenofibrate were second only to elafibranor and saroglitazar. Dohmen et al [ 50 ] found that in PBC patients refractory to UDCA, the effect of bezafibrate in decreasing the ALP levels was slightly superior to that of fenofibrate, which was generally consistent with the results of our network meta-analysis although not statistically significantly.In view of the fact that this is a small sample study, the reliability of conclusions needs to be further confirmed by high-quality large-size studies of the future.…”

Section: Discussionsupporting

confidence: 90%

“…UDCA plus budesonide was compared with UDCA monotherapy in one trial [ 30 ]. UDCA plus bezafibrate was compared with UDCA plus fenofibrate in one trial [ 50 ]. UDCA plus OCA was compared with UDCA monotherapy in three trials [ 24 , 25 , 51 ].…”

Section: Resultsmentioning

confidence: 99%

“…We performed a secondary analysis to assess the stability of the results by excluding studies in which participants’ ALP baseline levels differed significantly from other studies. We excluded five studies [ 13 , 42 – 44 , 50 ] for sensitivity analysis, and the results showed that elafibranor in combination with UDCA was the most likely (35%) to be the optimal drug regimens for improving ALP biochemical levels, followed by saroglitazar in combination with UDAC (21%). Differences in study design may lead to potential heterogeneity to a certain extent.…”

Section: Resultsmentioning

confidence: 99%

“…Differences in study design may lead to potential heterogeneity to a certain extent. We also excluded six non-RCT studies [ 10 , 45 , 46 , 48 – 50 ] for secondary analysis, and the results showed that saroglitazar in combination with UDCA was the most likely (24%) to be the optimal drug regimen for improving ALP biochemical levels, followed by elafibranor in combination with UDAC (23%). Sensitivity analyses did not change the ranking of the top two drug regimens, and the cumulative probability of the optimal and suboptimal drug regimens was always extremely close.…”

Section: Resultsmentioning

confidence: 99%

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Optimal drug regimens for improving ALP biochemical levels in patients with primary biliary cholangitis refractory to UDCA: a systematic review and Bayesian network meta-analysis

Lin,

Wang,

Liu

2024

Syst Rev

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Background Up to 40% of UDCA-treated patients do not have an adequate clinical response. Farnesoid X receptor agonists, peroxisome proliferator-activated receptor agonists, and fibroblast growth factor 19 analogs were developed as adjunctive therapy. The aim of this network meta-analysis was to compare the efficacy of these drugs as add-on therapy for patients with primary biliary cholangitis (PBC) refractory to UDCA in improving ALP levels. Methods We searched PubMed, Embase, Web of Science, and the Cochrane Library for eligible studies until 1 December 2023. Randomized controlled trials, cohort studies, and case–control studies comparing the efficacy of different combination treatments and UDCA monotherapy in UDCA-refractory PBC patients were included in the analysis. Cumulative probability was used to rank the included treatments. Results A total of 23 articles were eligible for our network meta-analysis. In terms of improving ALP levels, In terms of improving ALP biochemical levels, bezafibrate combined with UDCA (MD 104.49, 95% CI 60.41, 161.92), fenofibrate combined with UDCA (MD 87.81, 95% CI (52.34, 129.79), OCA combined with UDCA (MD 65.21, 95% CI 8.99, 121.80), seladelpar combined with UDCA (MD 117.39, 95% CI 19.97, 213.95), elafibranor combined with UDCA (MD 140.73, 95% CI 74.34, 209.98), saroglitazar combined with UDCA (MD 132.09, 95% CI 13.99, 247.04) was more effective than UDCA monotherapy. Elafibranor in combination with UDCA was the most likely (32%) to be the optimal drug regimen. Conclusion As second-line therapy for UDCA-refractory PBC, PPAR agonists were more effective than any other drugs with other mechanisms in improving ALP biochemical levels, with elafibranor being the best.

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Section: Discussionsupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Optimal drug regimens for improving ALP biochemical levels in patients with primary biliary cholangitis refractory to UDCA: a systematic review and Bayesian network meta-analysis

Lin,

Wang,

Liu

2024

Syst Rev

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“…A small study found that in patients with asymptomatic PBC, 48 weeks of treatment with low-dose fibrate (80 mg daily) and UDCA resulted in a comparable biochemical response to bezafibrate (200 mg daily) and UDCA. 89 …”

Section: Fibrates In the Treatment Of Pbcmentioning

confidence: 99%

The treatment of primary biliary cholangitis: from shadow to light

Sylvia,

Tomas,

Marian

et al. 2024

Therap Adv Gastroenterol

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Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic disease characterized by the destruction of the small intrahepatic bile ducts, which can progress to liver cirrhosis. The gold standard in the treatment of PBC is ursodeoxycholic acid (UDCA), which is indicated in all patients with PBC because it improves not only biochemical parameters but also patients’ survival. An important milestone in the identification of patients at risk is the assessment of biochemical response to UDCA. Patients who respond to treatment have a lower incidence of hepatic events and better prognosis than patients who do not. Several scoring systems can be used to assess the response and identify non-responders who will benefit from second-line treatment. Obeticholic acid (OCA) is currently the only approved second-line treatment for PBC, which is effective for non-responders to UDCA therapy or patients, who have not tolerated UDCA therapy. However, OCA is contraindicated in advanced liver cirrhosis and portal hypertension. Moreover, pruritus may be a limiting factor for the administration of OCA. Fibrates have shown promising data supporting their use in non-responders to UDCA because they improve the biochemical parameters and elastographic findings and have possible antipruritic effects. Therefore, the idea of a triple treatment seems interesting. Clinical research is focusing on several other groups of drugs: peroxisome proliferator-activated receptor (PPAR) δ- and α/δ agonists, non-steroidal farnesoid X receptor agonists, fibroblast growth factor 19 modulators, and inhibitors of nicotinamide adenine dinucleotide phosphate oxidase 1 and 4.

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Transition from Conventional Drugs to Promising Drugs for Primary Biliary Cholangitis

Dohmen¹

2017

ARGH

Self Cite

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The first known available therapeutic agent primary biliary cholangitis (PBC) is ursodeoxycholic acid (UDCA), which has been demonstrated to delay the development of fibrosis as well as improve survival in patients without the need for liver transplantation [1][2][3]. The optimal dosage of UDCA is 13-15mg/kg/ day and it is the standardized treatment for PBC. However, not all patients achieve a complete biochemical response to UDCA, and 10-20% will progress to cirrhosis or require liver transplantation. The most important merits of UDCA are lower costs and few adverse effects. BudesonideBudesonide is a glucocorticoid receptor/pregnane X receptor (PXR) agonist. Combination therapy of budesonide and UDCA was able to ameliorate the plasma biochemical index of hepatic function and hepatic histology, particularly in PBC patients with hepatic fibrosis, whereas the treatment effeciveness of UDCA alone was principally seen in laboratory results [4].

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Biochemical and Histological Effectiveness of Long-term Use of Fenofibrate for Asymptomatic Primary Biliary Cholangitis

Cited by 5 publications

References 41 publications

Optimal drug regimens for improving ALP biochemical levels in patients with primary biliary cholangitis refractory to UDCA: a systematic review and Bayesian network meta-analysis

Optimal drug regimens for improving ALP biochemical levels in patients with primary biliary cholangitis refractory to UDCA: a systematic review and Bayesian network meta-analysis

The treatment of primary biliary cholangitis: from shadow to light

Transition from Conventional Drugs to Promising Drugs for Primary Biliary Cholangitis

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