Many people with primary biliary cholangitis struggle with relentless itching. Standard treatment often stops working. A large review looked at six hundred sixty patients who had an inadequate response to ursodeoxycholic acid. The team tested three new medicines called PPAR agonists against a placebo. These drugs include bezafibrate, elafibranor, and seladelpar. The goal was to see if they could help control the worst symptom: itch. The results were clear. At three, six, and twelve months, the new drugs significantly reduced itch scores compared to the placebo. Patients felt relief when they took these medications. Safety signals were not reported in the study data. No serious adverse events or discontinuations were noted. However, the study could not prove these drugs improved overall quality of life. The certainty around this specific outcome was lower. This does not mean the drugs are unsafe, just that the full picture of daily life improvement needs more proof. Future trials should focus on validated symptom-focused endpoints to better understand patient experiences.
PPAR Agonists Reduce Pruritus in PBC: Meta-Analysis of 660 PatientsNew drugs ease itch for patients whose current treatment fails
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Key Takeaway
Consider PPAR agonists for pruritus reduction in PBC, but note uncertain effects on overall quality of life.
This systematic review and meta-analysis evaluated the efficacy of PPAR agonists (bezafibrate, elafibranor, seladelpar) versus placebo for pruritus in 660 patients with primary biliary cholangitis (PBC) who had an inadequate response to ursodeoxycholic acid. The primary outcomes were NRS and PBC-40 total score; secondary outcomes included PBC-40 itch-domain and 5D-itch score. Follow-up durations were 3, 6, and 12 months.
PPAR agonists significantly reduced NRS scores at all time points: at 3 months (MD, -1.39; 95% CI: -2.49 to -0.29), at 6 months (MD, -1.17; 95% CI: -1.96 to -0.38), and at 12 months (MD, -1.73; 95% CI: -3.00 to -0.46). However, the impact on overall health-related quality of life as measured by the PBC-40 total score could not be demonstrated, with a lower level of certainty.
Limitations noted by the authors include the inability to demonstrate an effect on global HRQoL and a lower level of certainty for that outcome. Adverse events, serious adverse events, and discontinuations were not reported. The authors underscore the need to incorporate validated, symptom-focused endpoints in future PBC trials.
Clinically, these findings support the use of PPAR agonists for pruritus in PBC patients with inadequate UDCA response, but the lack of demonstrated benefit on overall HRQoL warrants cautious interpretation.
What this means for you:
New drugs reduced itch scores in patients with primary biliary cholangitis who did not respond to standard treatment. More on Primary biliary cholangitis
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View Original Abstract ↓
BACKGROUND AND AIMS: Pruritus is a frequent and debilitating symptom in primary biliary cholangitis (PBC), substantially impairing sleep, mood and quality of life. Peroxisome proliferator-activated receptor (PPAR) agonists are promising second-line therapies for patients with an inadequate response to ursodeoxycholic acid (UDCA). We conducted a systematic review and meta-analysis to evaluate the efficacy of PPAR agonists on pruritus and health-related quality of life (HRQoL) in PBC.
METHODS: We systematically searched for randomised placebo-controlled trials (RCTs) of PPAR agonists in PBC through December 2025. Eligible studies reported validated pruritus or HRQoL outcomes. Main outcomes were NRS and PBC-40 total score. Pooled estimates were calculated using random-effects models and expressed as mean differences (MD) with 95% confidence intervals (CI).
RESULTS: Five RCTs evaluating bezafibrate, elafibranor and seladelpar (n = 660; 390 PPAR agonist; 270 placebo) met the inclusion criteria. For pruritus intensity analyses, data were restricted to participants with moderate-to-severe baseline symptoms (NRS ≥ 4) when available. PPAR agonists significantly reduced NRS scores at 3 months (MD, -1.39; 95% CI: -2.49 to -0.29), 6 months (MD, -1.17; 95% CI: -1.96 to -0.38) and 12 months (MD, -1.73; 95% CI, -3.00 to -0.46); in individual agent analyses, bezafibrate and seladelpar reached statistical significance at two or more time points. While improvements were also noted in PBC-40 itch-domain and 5D-itch score, an impact on overall HRQoL as reflected by PBC-40 total score could not be demonstrated, with a lower level of certainty.
CONCLUSIONS: PPAR agonists, notably bezafibrate and seladelpar, reduce pruritus severity in PBC patients with moderate-to-severe symptoms and consistently improve itch-specific outcomes. However, effects on global HRQoL remain uncertain. These findings underscore the incorporation of validated, symptom-focused endpoints in future PBC trials.
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