PPAR Agonists Reduce Pruritus in PBC: Meta-Analysis of 660 Patients
Photo by Navy Medicine / Unsplash
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.
More on Primary biliary cholangitis
Seladelpar shows improved composite endpoint and ALP reduction in PBC with compensated cirrhosis.
New Drug Helps Liver Disease Patients With Cirrhosis
A phase 3 RCT program (RESPONSE and ASSURE studies) in patients with primary biliary cholangitis and compensated cirrhosis found seladelpar …
A new drug lowers liver stress markers in patients with cirrhosis, offering hope where older medicines often failed to stop disease progress…
Narrative review on T cell subsets in primary biliary cholangitis
New Liver Drug Targets Hidden Immune Cells
This narrative review synthesizes evidence on T cell subsets in primary biliary cholangitis. It finds associations between T cell imbalances…
Stopping the wrong immune cells could finally stop liver disease for those who do not respond to standard care.
Hepatic steatosis prevalence and impact in autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis
Fatty liver makes autoimmune hepatitis and PBC worse, but not PSC.
This systematic review and meta-analysis of 19,898 patients with autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing c…
A large review found fatty liver is common in autoimmune liver diseases and makes outcomes worse for some patients, but not others.
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.
Immune Checkpoint Inhibitors Improve Survival and Response Rates in Patients with Hepatocellular Carcinoma Compared to Standard Therapy
New Drug Gives Liver Cancer Patients More Time
Related in Gastroenterology
Single 6 mg erdafitinib dose shows similar pharmacokinetics in mild or moderate hepatic impairment versus healthy controls.
Single dose of erdafitinib showed no dose changes needed for mild or moderate liver issues
This Phase 1 open-label single-dose study evaluated pharmacokinetics of erdafitinib in 26 participants with hepatic impairment versus health…
A single dose of erdafitinib worked well in people with mild or moderate liver problems, showing no need for dose adjustments.
Five ACLF diagnostic models and prognostic scores identified markedly different proportions of patients at risk of 28-day mortality in a cohort study.
Two new models find the sickest liver patients faster than old tools
This cohort study evaluated five acute-on-chronic liver failure (ACLF) diagnostic models and prognostic scores in 3,370 patients from the CO…
Two new scoring systems find the most dangerous liver failure patients better than older tools, potentially saving lives by catching risk ea…
SABR shows worse survival in ultracentral pulmonary oligometastases compared to nonultracentral tumors
Tumor location matters: ultracentral spots linked to worse survival in lung metastasis patients
This secondary analysis of the SABR-5 Phase 2 trial evaluated progression-free and overall survival in 41 patients with ultracentral pulmona…
Tumor location matters. Patients with ultracentral lung metastases had shorter survival times than those with nonultracentral spots after ra…
SABR in oligometastatic cancer showed median overall survival of 64.6 months in a single-arm phase 2 study.
SABR offers five-year survival hope for patients with limited cancer spread
This single-arm phase 2 trial evaluated stereotactic ablative radiotherapy (SABR) in 380 patients with oligometastatic cancer across six Can…
Patients with few cancer spots lived longer with SABR treatment. Five-year survival reached 58.6 percent in this Canadian study.
From Other Specialties
Systematic review and meta-analysis shows immune checkpoint inhibitors improve survival in first-line ES-SCLC but not as single agents in second-line
Immune drugs boost survival in small-cell lung cancer
This systematic review and meta-analysis evaluates immune checkpoint inhibitors combined with chemotherapy versus chemotherapy alone for ext…
Adding immune checkpoint inhibitors to chemotherapy helps patients with extensive-stage small-cell lung cancer live longer.
Network meta-analysis of anti-PD-1/PD-L1 regimens in advanced non-squamous NSCLC without EGFR or ALK alterations
New drugs beat old ones for advanced lung cancer survival
This systematic review and network meta-analysis evaluated overall survival and progression-free survival across 15 Phase III randomized cli…
New drug combinations show better survival chances for advanced lung cancer patients whether their tumors express PD-L1 or not
Lung Ultrasound Shows Good Diagnostic Accuracy for ARDS in Meta-Analysis of 5888 Patients
Lung ultrasound shows high accuracy for detecting severe breathing trouble in ICU patients
This systematic review and meta-analysis of 5888 patients found that lung ultrasound (LUS) has good diagnostic accuracy for acute respirator…
A large review of 5,888 patients found lung ultrasound is a highly accurate, safe way to check for severe lung injury without using radiatio…
Kidney-directed SBRT shows modest renal function decline in inoperable patients
Small study shows kidney function drops after radiation for hard-to-treat tumors
This prospective phase 2 single-arm trial evaluated kidney-directed SBRT in 30 patients with primary or metastatic renal tumors who were med…
Radiation to treat kidney tumors may lower kidney function over two years, even when surgery is not an option.