New and emerging treatments for PBC-related pruritus.

内容摘要

Pruritus is an early and often debilitating symptom of primary biliary cholangitis (PBC), significantly impairing quality of life through fatigue, sleep disturbance, anxiety and social withdrawal. Traditional management relies on a stepwise approach, with bile acid sequestrants as first-line therapy and rifampin, naltrexone, or sertraline for refractory cases, but these agents often provide incomplete relief and are limited by tolerability and drug-drug interaction concerns. Advances in understanding the mechanisms of cholestatic itch have expanded treatment options to include peroxisome proliferator-activated receptor (PPAR) agonists, such as seladelpar, elafibranor and bezafibrate that uniquely offer both antipruritic effects and improvement in biochemical markers of disease activity. Therapies targeting specific pruritogenic pathways now include ileal bile acid transporter (IBAT) inhibitors, one of which is now approved specifically for PBC-related pruritus, as well as κ-opioid receptor agonists, MrgprX4 antagonists, and autotaxin inhibitors. Optimal management integrates pharmacological therapy with supportive strategies, including skin care, lifestyle modifications and psychosocial support tailored to the individual patient's disease activity, symptom severity, and comorbidities. By addressing both the biological and experiential dimensions of pruritus, this comprehensive framework enables clinicians to improve symptom control and enhance overall quality of life for patients living with PBC. Emerging therapies and a mechanism-informed treatment approach offer promise for more effective, individualized care in this challenging clinical context. Primary biliary cholangitis (PBC) is a long-term liver disease that often causes severe itching (called pruritus). This itching can begin early in the disease and significantly affect daily life by disrupting sleep, causing fatigue, and contributing to anxiety or social withdrawal. Unfortunately, treatments traditionally used to manage this symptom do not work well for many patients or can cause side effects. For years, healthcare professionals have followed a step-by-step approach to treat PBC-related itching. The first option is usually medications that bind bile acids in the gut (such as cholestyramine). If these do not help, other drugs like rifampin, naltrexone or sertraline may be tried. However, these treatments are often only partly effective and may interact with other medications or cause safety concerns. Recent research has improved understanding of why itching occurs in PBC. Rather than being caused by a single factor, it appears to involve multiple pathways, including bile acids, nerve signalling and certain molecules in the blood. This has led to the development of newer treatments that target these underlying mechanisms more directly. Among the most promising newer therapies are drugs called PPAR agonists, which not only help reduce itching but also improve liver disease activity. Another class of drugs, called IBAT inhibitors (such as linerixibat and volixibat), works by reducing bile acid levels and has also shown benefit, although side effects like diarrhoea are common. Other experimental treatments, including drugs targeting opioid receptors, specific itch receptors or enzymes involved in itch signalling, are still being studied and are not yet widely available. Managing PBC-related itching often requires a personalized approach. In addition to medications, supportive strategies such as skin care, avoiding heat, wearing loose clothing, and addressing sleep or mental health issues are important. Overall, newer therapies and a better understanding of the causes of PBC-related itching are helping to improve treatment options. These advances offer hope for more effective and individualized care, ultimately improving quality of life for people living with PBC.