PUB - Publikationen an der Universität Bielefeld

Goals: We aim to summarize the current management of pruritus in primary biliary cholangitis (PBC) by evaluating the efficacy and safety of pharmacological therapies. Background: Pruritus is a common symptom of PBC, and evidence regarding the most effective antipruritic agents available is lacking. New pharmacotherapy for PBC has shown promising antipruritic effects. Study: We performed a systematic literature review and meta-analysis including all available double-blind, randomized, placebo-controlled clinical trials that evaluated the efficacy of pharmacotherapy for the symptomatic management of pruritus in PBC. Pruritus was assessed as either a change from baseline or a postintervention score. Results: We included 33 studies and 20 medications. Using the visual analog scale, cholestyramine did not significantly improve pruritus compared with placebo [standardized mean differences (SMD): −0.94, 95% CI: −2.05 to 0.17], whereas rifampin and nalfurafine hydrochloride both significantly improved pruritus (SMD: −3.29, 95% CI: −5.78 to −0.80; n=23 and SMD: −0.58, 95% CI: −1.04 to −0.12). In addition, Bezafibrate and linerixibat significantly improved pruritus (SMD: −1.05, 95% CI: −1.41 to −0.68; n=110 and SMD: −0.31, 95% CI: −0.62 to −0.04, respectively). This effect was also present within the subgroup analysis by pruritus scale, where both bezafibrate and linerixibat significantly improved pruritus compared with placebo (SMD: −1.09, 95% CI: −1.54 to −0.65; P<0.001; visual analog scale; as postintervention score and SMD: −0.31, 95% CI: −0.62 to −0.01; P=0.04; numeric rating scale; as a change from baseline score, respectively). Conclusions: Bezafibrate and Linerixibat are potential second-line antipruritic medications for PBC, particularly those with moderate to severe pruritus. Primary biliary cholangitis (PBC) is a chronic, immune-mediated liver disease characterized by destruction of intrahepatic bile ducts, and is associated with numerous extrahepatic complications.1 Approximately 60% to 70% of patients diagnosed with PBC experience pruritus at some point during their disease course, and nearly 35% have refractory pruritus.2 Pruritus can lead to sleep deprivation, fatigue, and emotional disturbances including depression and suicidal ideation, all of which leads to lower health-related quality of life (HRQoL).3 Successful symptomatic treatment of pruritus can improve patients’ quality of life, and is an essential component of the overall management of PBC. Treatment options for pruritus in patients with PBC are limited. Ursodeoxycholic acid (UDCA) has been shown to favorably alter the natural history of PBC, but its effect on pruritus has not been proven.4 To achieve improved control of pruritus in patients with cholestasis, the American Association for the Study of Liver Disease (AASLD) and the European Association for the Study of the Liver (EASL) recommend a step-wise pharmacological approach. Cholestyramine is considered/first-line therapy for pruritus. Rifampin, naltrexone, and sertraline are all recommended as potential second-line options.4,5 However, these medications lack adequate efficacy for the treatment of pruritus, and have unfavorable side effect profiles, which have prompted additional studies exploring novel treatment options. Novel medications have expanded the potential treatment options for the management of symptomatic pruritus in PBC. Ileal bile acid transport (IBAT) inhibitors and peroxisome proliferator-activated receptor agonists have both shown promising results in recent studies.6–9 Other novel therapeutics have also been studied. We performed a systematic review and meta-analysis of all randomized-controlled trials (RCTs) studying antipruritic medications used in PBC patients.