Efficacy and safety of pharmacological interventions for pruritus in primary biliary cholangitis: A systematic review and meta-analysis

Abstract

Background and objective: Pruritus is a common complication in patients with primary biliary cholangitis (PBC). The pathogenesis is not clear, and also the precise therapeutic measures remain alluring. In order to systematically evaluate the efficacy and safety of drug interventions in the treatment of pruritus associated with PBC, this systemic review and meta-analysis was conducted.Methods: The randomized controlled trials (RCTs) on drug interventions in the treatment of pruritus associated with primary cholangitis were searched in the electronic databases of PubMed, EMBASE, Cochrane Library, Web of Science, and ClinicalTrials.gov. Two researchers independently screened the literature, extracted and integrated the data, and assessed the bias risk of the selected literature, according to the Cochrane handbook. Finally, the STATA 15.0 software was used for the meta-analysis.Results: A total of 23 RCTs involving 2,194 patients were studied, that included 12 pharmacological interventions. In terms of itching relief, compared with placebo, UDCA, methotrexate and GSK2330672 had a definite effect in improving pruritus (pruritus remission rate before and after treatment, p < 0.05). In terms of serum indexes, compared with placebo group, UDCA, OCA, rifampicin, cyclosporine, NGM282, seladelpar and colchicine may improve blood alkaline phosphatase (ALP) (p < 0.05), but only rifampicin showed low heterogeneity. UDCA, bezafibrate, OCA, rifampicin, NGM282 and others may improve blood γ-glutamyl transpeptidase (γ-GGT) (p < 0.05), but due to the high heterogeneity and the limitation of research samples, a clear conclusion cannot be drawn. In terms of adverse events, except high (>15 mg/kg/day) and low doses (<13 mg/kg/day) of UDCA increased the incidence of adverse events, there were no risk of increasing the incidence of adverse events compared with placebo (p > 0.05), and a moderate dose of UDCA (13–15 mg/kg/day) and malotilate (1,500 mg/day) may also help in reducing the incidence of adverse events (p < 0.05).Conclusion: UDCA, methotrexate and GSK2330672 may relieve itching in patients with PBC, but there is a lack of robust evidence to support their effect on ALP or γ-GGT. Due to the heterogeneity in the published studies, based on the present review, we cannot explicitly recommend any specific drug for the treatment of PBC-related pruritus.Systematic Review Registration:link-https://osf.io/2g8ya, identifier 10.17605/OSF.IO/2G8YA

Primary biliary cirrhosis and psoriasis: a two-sample Mendelian randomization study

“…For patients suffering from both PBC and psoriasis, interdisciplinary collaboration among medical professionals is essential for timely diagnosis and optimal treatment. A systematic review and meta-analysis published in 2022 identified several medications effective in alleviating PBC-related pruritus ( 24 ), including ursodeoxycholic acid (UDCA), methotrexate (MTX), and GSK2330672, an intestinal bile acid transporter inhibitor. These drugs significantly reduced pruritus scores or provided pruritus relief.…”

Ursodeoxycholic acid induces sarcopenia associated with decreased protein synthesis and autophagic flux

“…In humans, a UDCA dose within the range of 8–15 mg/kg/day has been used effectively to treat primary biliary cholangitis or gallstones [ 41 , 42 ]. In this work, we used equivalent doses to those used in humans, efficiently reducing gallstones, cholestasis, and intestinal inflammation in other mice models [ 43 – 46 ].…”