For patients with primary biliary cholangitis (PBC), a combination of fenofibrate and ursodeoxycholic acid (UDCA) resulted in a significantly higher biochemical response rate, a study found.
Researchers in China recruited 117 treatment-naive patients with PBC who met two of three criteria: presence of antimitochondrial antibody or other PBC-associated autoantibodies, including sp100 or gp210; elevation of alkaline phosphatase (ALP) level; and compatible or diagnostic liver histology. Study participants were randomized open-label to either UDCA at a standard dose (UDCA-only group) or fenofibrate at a daily dose of 200 mg in addition to UDCA (combination group). The primary outcome was biochemical response at 12 months. Results were published in the November American Journal of Gastroenterology.
Based on the Barcelona criteria, 81.4% (95% CI, 69.9% to 92.9%) of patients in the combination group achieved the primary outcome versus 64.3% (95% CI, 51.9% to 76.8%) in the UDCA-only group (P=0.048). In an analysis with last-observation-carried-forward imputation, 86.0% (95% CI, 74.4% to 92.7%) of patients in the combination group achieved the primary outcome compared to 63.3% (95% CI, 50.7% to 74.4%) of patients in the UDCA-only group (P=0.005). Biochemical response rates gradually increased in the UDCA-only group, reaching a plateau of 65% at month 9. The response rate in the combination group was above 80% at month 1 (88.5% vs. 45.3%; P<0.001) and remained stable throughout the study.
The two groups did not differ in noninvasive measures of liver fibrosis and biochemical markers besides ALP level at 12 months. At month 12, 62% (95% CI, 48% to 75%) of patients in the UDCA-fenofibrate group had a normal ALP level versus 40% (95% CI, 28% to 53%) in the UDCA-only group (P=0.042), consistent with the results for the primary outcome. Creatinine and aminotransferase levels in the combination group increased within the first month, returned to normal, and remained stable thereafter until the end of the study, even in patients with cirrhosis, the study authors noted.
Limitations include that the study was conducted at a single center with a small sample size and no placebo blinding. In addition, it did not analyze long-term survival and patients did not undergo paired liver biopsy at baseline and after fenofibrate treatment, limiting understanding of the effect of fibrates on liver histology, the authors noted. “Consistent with previous studies, our results confirmed that fenofibrate showed good efficacy at normalizing ALP levels, which is the most important prognostic indicator of PBC,” they wrote. “No increase in [total bilirubin] level was observed in patients treated with fenofibrate during the study.”