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

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.

• Authors: Andreas E Kremer, Marlyn J Mayo, Gideon Hirschfield, Cynthia Levy, Christopher L Bowlus, David E Jones, Alexandra Steinberg, Charles A McWherter, Yun-Jung Choi
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 42 Issue 1 Pg. 112-123 (01 2022) ISSN: 1478-3231 [Electronic] United States
• PMID: 34403559 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Liver International published by John Wiley & Sons Ltd.

Chemical References

• Acetates
• Bile Acids and Salts
• seladelpar

Topics

• Acetates
• Bile Acids and Salts (therapeutic use)
• Fatigue (drug therapy, etiology)
• Humans
• Liver Cirrhosis, Biliary (complications, drug therapy)
• Pruritus (drug therapy, etiology)
• Quality of Life
• Sleep
• Treatment Outcome