S2667 Safety Profile of Placebo in Patients With Primary Biliary Cirrhosis: A Systematic Review and Meta-Analysis

Introduction: Primary biliary cirrhosis (PBC) is a chronic autoimmune liver disease for which several therapies are under investigation. Placebo-controlled trials are commonly used to evaluate the efficacy of new treatments, but a clear understanding of the safety profile of placebo in this population is limited. This meta-analysis aimed to systematically assess the incidence and nature of adverse events associated with placebo administration in patients with PBC. Methods: This systematic review and meta-analysis was conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive literature search was performed to identify randomized controlled trials (RCTs) reporting adverse events in the placebo arms of studies involving patients with primary biliary cirrhosis (PBC). Articles were searched from inception to April 2025 across 5 electronic databases: PubMed, Google Scholar, Scopus, Embase, and Cochrane Central Register of Controlled Trials. Descriptive statistics were used to calculate pooled event rates, which were expressed as percentages of the total placebo population. Results: A total of 10 randomized controlled trials were included in this meta-analysis, comprising 633 patients who received placebo for the treatment of primary biliary cirrhosis. The analysis focused on the incidence of adverse events reported in the placebo arms. The most commonly observed adverse event was pruritus, reported in 17.2% of patients (109 cases). Other frequent adverse events included headache (5.2%), nausea (5.1%), abdominal pain (3.6%), diarrhea (3.5%), and urinary tract infections (UTI) (3.0%). Less common adverse events were nasopharyngitis (2.2%), arthralgia (1.4%), and upper respiratory tract infections (URTI) (1.3%). Rarely reported events included constipation (0.8%), abdominal distension (0.5%), and insomnia (0.2%). Conclusion: This meta-analysis demonstrates that a placebo is generally safe and well-tolerated in patients with primary biliary cirrhosis. Most adverse events were mild, infrequent, and self-limiting.