Seladelpar improved measures of pruritus, sleep, and fatigue and decreased serum bile acids in patients with primary biliary cholangitis

摘要

Abstract Background & Aims Primary biliary cholangitis (PBC) can result in life‐altering cholestatic pruritus and fatigue, but treatment options are limited. Seladelpar, a peroxisome proliferator‐activated receptor‐delta (PPARδ) agonist, has demonstrated potent anti‐cholestatic effects in clinical studies. This open‐label, uncontrolled phase 2 study in PBC patients evaluated the effects of 1‐year of seladelpar treatment on measures of pruritus and quality of life. Methods Self‐reported experiences of 101 PBC patients were collected at baseline and after 1?year of seladelpar treatment using the pruritus visual analog scale (VAS), 5D‐itch scale, and PBC‐40 questionnaires along with bile acid profiles. Results In patients with moderate–to‐severe pruritus, substantial improvement in pruritus was seen in 58% and 93% of patients in 5/10?mg and 10?mg treatment groups, respectively. After 1?year, patients reporting improvement substantially outnumbered those who worsened in the total 5‐D itch (including individual domains) and PBC‐40 (itch and fatigue domains) questionnaires. Improvement in sleep disturbance at 1‐year was reported in 81% (5/10?mg) and 78% (10?mg) of the patients with baseline itch‐related sleep disturbance by 5‐D itch score with similar results using the PBC‐40 sleep questionnaire. Seladelpar‐treated patients had significant reductions of 46% (5/10?mg) and 31% (10?mg) in the serum bile acid precursor C4 and reductions of up to 38% in serum bile acids. Conclusions Seladelpar treatment for 1?year led to consistent improvement in both symptom burden and biochemical response, suggesting its potential as a single agent to address two key unmet needs in PBC patients.