Treatment of primary biliary cholangitis ursodeoxycholic acid non‐responders: A systematic review

Suraweera, Duminda; Rahal, Harman; Jimenez, Melissa; Viramontes, Matthew R.; Choi, Gina; Saab, Sammy

doi:10.1111/liv.13477

Cited by 27 publications

(20 citation statements)

References 55 publications

(98 reference statements)

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“…Fenofibrate [109] and bezafibrate [110] were shown to improve liver function test in patients with PBC. Given the favorable effects of pemafibrate on liver function test values in patients with dyslipidemia, it may also improve liver function in patients with PBC.…”

Section: Effects Of Pemafibrate On Primary Biliary Cholangitis (Pbc)mentioning

confidence: 96%

Pemafibrate, a New Selective PPARα Modulator: Drug Concept and Its Clinical Applications for Dyslipidemia and Metabolic Diseases

Yamashita¹,

Masuda²,

Matsuzawa

2020

Curr Atheroscler Rep

126

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Purpose of Review Reduction of serum low-density lipoprotein cholesterol (LDL-C) levels by statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors has been shown to significantly reduce cardiovascular events risk. However, fasting and postprandial hypertriglyceridemia as well as reduced high-density lipoprotein cholesterol (HDL-C) remain as residual risk factors of atherosclerotic cardiovascular diseases (ASCVD). To treat patients with hypertriglyceridemia and/or low HDL-C, drugs such as fibrates, nicotinic acids, and n-3 polyunsaturated fatty acids have been used. However, fibrates were demonstrated to cause side effects such as liver dysfunction and increase in creatinine levels, and thus large-scale clinical trials of fibrates have shown negative results for prevention of ASCVD. The failure could be attributed to their low selectivity and potency for binding to peroxisome proliferator-activated receptor (PPAR) α. To resolve these issues, the concept of selective PPARα modulator (SPPARMα) with a superior balance of efficacy and safety has been proposed and pemafibrate (K-877) has been developed. Recent Findings Pemafibrate, one of SPPARMsα, was synthesized by Kowa Company, Ltd. for better efficiency and safety. Clinical trials in Japan have established the superiority of pemafibrate on effects on serum triglycerides (TG) reduction and HDL-C elevation as well safety. Although available fibrates showed worsening of liver and kidney function test values, pemafibrate indicated improved liver function test values and was less likely to increase serum creatinine or decrease estimated glomerular filtration rate (eGFR). Very few drug-drug interactions were observed even when used concomitantly with statins. Furthermore, pemafibrate is metabolized in the liver and excreted into the bile, while many of available fibrates are mainly excreted from the kidney. Therefore, pemafibrate can be used safely even in patients with impaired renal function since there is no significant increase in its blood concentration. A large-scale trial of pemafibrate, PROMINENT, for dyslipidemic patients with type 2 diabetes is ongoing. Summary Pemafibrate is one of novel SPPARMsα and has superior benefit-risk balance compared to conventional fibrates and can be applicable for patients for whom the usage of existing fibrates is difficult such as those who are taking statins or patients with renal dysfunction. In the current review, all the recent data on pemafibrate will be summarized.

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Section: Effects Of Pemafibrate On Primary Biliary Cholangitis (Pbc)mentioning

confidence: 96%

Pemafibrate, a New Selective PPARα Modulator: Drug Concept and Its Clinical Applications for Dyslipidemia and Metabolic Diseases

Yamashita¹,

Masuda²,

Matsuzawa

2020

Curr Atheroscler Rep

126

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“…Ursodeoxycholic acid (UDCA) is the first‐line treatment for PBC . The use of UDCA slows disease progression and improves outcomes, especially in patients with mild histologic changes and good biochemical response . Nevertheless, there is a group of patients with PBC who do not respond optimally to UDCA.…”

mentioning

confidence: 99%

“…(18) The use of UDCA slows disease progression and improves outcomes, especially in patients with mild histologic changes and good biochemical response. (18)(19)(20)(21)(22) Nevertheless, there is a group of patients with PBC who do not respond optimally to UDCA. This prompted a number of efforts to develop additional investigational agents for PBC.…”

mentioning

confidence: 99%

Primary Biliary Cholangitis in Medicare Population: The Impact on Mortality and Resource Use

et al. 2019

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“…15 years; range, 40–280 months [3–23 years]) in the overall study cohort. To our knowledge, this is the study with the longest duration among those already published (3–113 months [0–9 years]) …”

Section: Resultsmentioning

confidence: 99%

“…To our knowledge, this is the study with the longest duration among those already published (3-113 months [0-9 years]). 28,29 Biochemical responses. The biochemical response to combination therapy is shown in Figure 2a, and a significant improvement in these parameters was observed at as early as 3 months after combination therapy and continued throughout the 24-month period, suggesting that a significant improvement in biochemistry could be achieved in the first 3 months of combination therapy.…”

Section: Resultsmentioning

confidence: 99%

IgM response is a prognostic biomarker of primary biliary cholangitis treated with ursodeoxycholic acid and bezafibrate

Takano

Saeki

Oikawa

et al. 2019

J of Gastro and Hepatol

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Background and Aim Primary biliary cholangitis (PBC) patients who are refractory to ursodeoxycholic acid (UDCA) are at risk for progression to cirrhosis and liver failure. Bezafibrate could be an alternative second‐line therapeutic option in these patients. This study aimed to evaluate the long‐term outcome(s) of combined UDCA and bezafibrate therapy in UDCA‐refractory PBC patients and identify prognostic factors. Methods Among 445 patients treated with UDCA, 150 patients inadequately responded to UDCA monotherapy and received long‐term UDCA plus bezafibrate (median, 15 years). Data from these patients were used for this retrospective analysis. Results Combination therapy resulted in significant improvements in serum biochemistry and liver transplantation risk estimated using the UK‐PBC‐risk and the GLOBE scores. The cumulative normalization rates of alkaline phosphatase, gamma‐glutamyltransferase, and immunoglobulin M (IgM) were significantly higher in patients without cirrhosis‐related symptoms or liver‐related events than in those with them. Overall, IgM constantly emerged as a significant factor associated with cirrhosis‐related symptoms and liver‐related events at all time points. Cumulative survival rates were significantly lower in patients with IgM ≥ 240 mg/dL than in patients with IgM < 240 mg/dL. Thus, normalization of IgM levels was a good surrogate predictor of long‐term prognosis. None of the patients discontinued combination therapy due to any adverse events during the follow‐up period. Conclusions Our findings point to the beneficial effects of long‐term UDCA plus bezafibrate combination therapy for UDCA‐refractory PBC patients, and IgM response can be a useful predictive biomarker of long‐term clinical outcomes.

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Treatment of primary biliary cholangitis ursodeoxycholic acid non‐responders: A systematic review

Cited by 27 publications

References 55 publications

Pemafibrate, a New Selective PPARα Modulator: Drug Concept and Its Clinical Applications for Dyslipidemia and Metabolic Diseases

Pemafibrate, a New Selective PPARα Modulator: Drug Concept and Its Clinical Applications for Dyslipidemia and Metabolic Diseases

Primary Biliary Cholangitis in Medicare Population: The Impact on Mortality and Resource Use

IgM response is a prognostic biomarker of primary biliary cholangitis treated with ursodeoxycholic acid and bezafibrate

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