Peroxisome proliferator-activated receptor (PPAR) agonists appears to be a safe and effective therapeutic alternative for patients with primary biliary cholangitis (PBC), according to a recently published study in Therapeutic Advances is Gastroenterology.
PBC is a chronic autoimmune liver disease that targets small intrahepatic bile ducts, often leading to biliary acid accumulation (cholestasis), scarring (fibrosis) and eventually cirrhosis or liver failure.
While ursodeoxycholic acid (UDCA) remains the first-line treatment for PBC, up to 40% of patients respond inadequately or experience severe side effects. Furthermore, UDCA’s impact on itchiness (pruritus), a debilitating symptom in PBC, is limited. A treatment alternative, obeticholic acid, has faced restrictions due to safety concerns, and was pulled from U.S. markets last week.
Studies have shown the therapeutic potential of PPAR agonists. PPARs are proteins involved in bile acid metabolism and inflammation. However, individual studies had small sample sizes and varied results.
To address this gap, the authors conducted a systematic review and meta-analysis to comprehensively evaluate the efficacy and safety of PPAR agonists in patients with PBC. Meta-analyses and systematic reviews combine the results of several studies on a given subject to increase the statistical strength of the results.
Researchers screened four major databases through October 2024 and included 14 randomized controlled trials comprising 1,137 patients. Eligible studies assessed at least one of the following: change in alkaline phosphatase (ALP), biochemical response, pruritus relief or severe/serious adverse events (AEs). Subgroup analyses were conducted by drug type and treatment duration.
The results revealed that PPAR agonists significantly reduced ALP levels compared to a placebo, and increased biochemical response rates. These effects remained consistent across different drugs and treatment durations. Subgroup data showed that in particular, the PPAR agonists bezafibrate and seladelpar were particularly effective in lowering ALP levels.
The authors noted that pruritus relief was inconsistent across trials. Seladelpar and elafibranor significantly improved symptoms when evaluated using validated scales like the NRS and 5-D itch scale. However, some agents such as bezafibrate showed no significant benefit on itch intensity.
“In patients with PBC, PPAR agonists significantly reduced the ALP levels and improved the biochemical response rates, irrespective of drug type and treatment duration. PPAR agonists appear safe and well-tolerated by patients with PBC,” the authors concluded.
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