Safety and efficacy of switching to pemafibrate from bezafibrate in patients with chronic liver disease

Abstract

Aim Although fibrates were developed as lipid‐lowering drugs, their efficacy against liver dysfunction in patients with cholestatic liver diseases, such as primary biliary cholangitis, primary sclerosing cholangitis, and fatty liver disease, has also been reported. Although fibrates act on some peroxisome proliferator‐activated receptors (PPARs), pemafibrate is a novel selective PPAR‐α modulator. The present study aimed to evaluate the safety and efficacy of switching from bezafibrate to pemafibrate in patients with chronic liver disease. Methods We analyzed 58 patients with chronic liver disease who switched from bezafibrate to pemafibrate because of minor adverse effects and/or incomplete response. Results This study included 41 patients with cholestatic liver disease and 17 patients with non‐alcoholic fatty liver disease. Reasons for switching to pemafibrate were renal function decline in 31 patients, hemoglobin decline in 17 patients, creatine kinase (CK) elevation in 11 patients, incomplete response of liver dysfunction in 39 patients, and incomplete response of hyperlipidemia in 13 patients. After 3 months, although no significant change in CK was seen, hemoglobin and estimated glomerular filtration rate were significantly increased, and creatinine was significantly decreased. Significant decreases in hepatobiliary enzymes were seen in patients with cholestatic liver diseases, but not in patients with non‐alcoholic fatty liver disease. No significant changes in serum lipids were observed. No patients discontinued pemafibrate due to adverse events. Conclusions Switching to pemafibrate could improve adverse effects due to bezafibrate, and appeared effective against liver dysfunction in cholestatic liver disease patients with incomplete response to bezafibrate.

Mechanism-based target therapy in primary biliary cholangitis: opportunities before liver cirrhosis?

“…Pemafibrate, a new selective PPARα modulator, was recommended for treating PBC with dyslipidemia, or for patients with poor response to UDCA monotherapy or bezafibrate plus UDCA combination treatment ( 141 ). It is also noted that switching from Fenofibrate or bezafibrate to Pemafibrate reduced adverse effects for patients with incomplete response or some renal disorder ( 142 , 143 ).…”

Effectiveness of 1-year pemafibrate treatment on steatotic liver disease: the influence of alcohol consumption

“…Pemafibrate is a selective peroxisome proliferator-activated receptor (PPAR) α modulator that was designed to have greater PPARα agonistic activity and selectivity than existing PPARα agonists [7,8]. Recent animal studies suggest that PPARα has anti-inflammatory properties through transrepression of pro-inflammatory target genes, such as activator protein (AP)-1 and nuclear factor (NF)-κB [9].…”

The metabolic evaluation of pemafibrate in nonalcoholic fatty liver disease‐related cardiovascular diseases

“…The metabolic evaluation of pemafibrate in nonalcoholic fatty liver disease-related cardiovascular diseases Tamai and Okamura indicated that the novel selective peroxisome proliferator-activated receptor (PPAR)α modulator, pemafibrate improved adverse effects and incomplete response, and had more beneficial safety and efficacy in patients with chronic liver diseases compared with bezafibrate, including creatinine, hemoglobin, and estimated glomerular filtration rate. 1 Moreover, the therapeutic response of pemafibrate was superior to bezafibrate in the improvement of metabolism dysfunction-related cardiovascular events due to enhanced PPARα activity and specificity, 2 but the effects of pemafibrate on the metabolic association between chronic liver diseases and cardiovascular diseases (CVD) were not investigated and should be emphasized. Thus, I have some opinions on the metabolic modulation of pemafibrate against nonalcoholic fatty liver disease (NAFLD)-related CVD.…”