Safety profile of elafibranor versus placebo in primary biliary cholangitis: A systematic review, meta-analysis, and trial sequential analysis of randomized controlled trials

While elafibranor's safety has been addressed within a 3 outcome network meta-analysis of second-line primary biliary cholangitis (PBC) agents and within a mixed design review using serious adverse events (AEs) as its sole safety endpoint, no review has yet applied trial sequential analysis (TSA) or Grading of Recommendations Assessment, Development and Evaluation (GRADE) certainty assessment to a dedicated, 10-outcome, placebo-controlled elafibranor evidence base. PBC is a chronic autoimmune liver disease affecting the small bile ducts, with approximately 30% to 40% of patients failing to respond adequately to first-line ursodeoxycholic acid (UDCA) therapy. Elafibranor, a dual peroxisome proliferator-activated receptor α/δ agonist, received Food and Drug Administration and European Medicines Agency approval in 2024 as a second-line option, yet no pooled randomized evidence for its safety profile had been synthesized.