Change in pruritus in patients with primary biliary cholangitis and moderate to severe pruritus: a pooled analysis from the RESPONSE and ENHANCE studies

D E Jones; C Levy; A E Kremer; A Ladron de Guevara Cetina; A Villamil; E Janczewska; M Rabinovitz; P Andreone; X Qi; S Carroll; T R Watkins; M J Mayo

doi:10.1055/s-0045-1810776

Zeitschrift für Gastroenterologie, Table of Contents

Z Gastroenterol 2025; 63(08): e455
DOI: 10.1055/s-0045-1810776

Abstracts | DGVS/DGAV

Kurzvorträge

Autoimmune und cholestatische Lebererkrankungen: neue Wege in der Behandlung Freitag, 19. September 2025, 14:45 – 16:21, Seminarraum 14 + 15

Change in pruritus in patients with primary biliary cholangitis and moderate to severe pruritus: a pooled analysis from the RESPONSE and ENHANCE studies

Authors

D E Jones

¹Translational and Clinical Research Institute and Centre for Rare Disease, Newcastle University, Newcastle upon Tyne, Vereinigtes Königreich
C Levy

²Division of Digestive Health and Liver Diseases, University of Miami School of Medicine, Miami, Vereinigte Staaten
A E Kremer

³Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Schweiz
A Ladron de Guevara Cetina

⁴Centro de Investigación y Gastroenterología, Hospital Angeles Clinica Londres, Mexico City, Mexiko
A Villamil

⁵The Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentinien
E Janczewska

⁶Department of Basic Medical Sciences, Faculty of Public Health in Bytom, Medical University of Silesia, Bytom, Polen
M Rabinovitz

⁷Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, Vereinigte Staaten
P Andreone

⁸Division of Internal Medicine, Università di Modena e Reggio Emilia, Modena, Italien
X Qi

⁹Gilead Sciences, Inc., Foster City, Vereinigte Staaten
S Carroll

⁹Gilead Sciences, Inc., Foster City, Vereinigte Staaten
T R Watkins

⁹Gilead Sciences, Inc., Foster City, Vereinigte Staaten
M J Mayo

¹⁰Division of Digestive and Liver Diseases, University of Texas Southwestern, Dallas, Vereinigte Staaten

Abstract

Full Text

Introduction: Seladelpar (SEL) is a first-in-class delpar (selective PPAR-delta agonist) indicated for the treatment of PBC in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA, or as a monotherapy in pts unable to tolerate UDCA. In two Phase 3, placebo (PBO)-controlled trials (ENHANCE [NCT03602560] and RESPONSE [NCT04620733]), SEL significantly reduced pruritus among pts who had moderate to severe pruritus (numerical rating scale [NRS]≥4) at baseline (BL).

Objectives: Here, we present pooled pruritus outcomes across different measures of itch in pts with PBC from RESPONSE and ENHANCE with NRS≥4 at BL.

Methodology: Pts with PBC were randomised 1:1:1 to daily SEL 5 mg, SEL 10 mg, or PBO for 52 weeks in ENHANCE and 2:1 to daily SEL 10 mg or PBO for 52 weeks in RESPONSE (ENHANCE terminated early with key endpoints amended to month [M] 3). Pooled data from pts with NRS≥4 at BL who received SEL 10 mg or PBO in RESPONSE and at least 6 M in ENHANCE were analysed. In a post hoc analysis, changes across several measures of itch up to M6 (NRS, PBC-40 itch domain, and the 5-D itch scale) were assessed.

Results: Of the 126 pts with moderate to severe pruritus, 76 and 50 received SEL 10 mg and PBO, respectively, in RESPONSE or ENHANCE. Most pts at BL were<50 years old at age of PBC diagnosis (73/126) and had a history of pruritus (122/126) and fatigue (77/126). NRS, PBC-40 itch domain, and 5-D itch scale scores were similar between the SEL and PBO groups at BL. At M6, pts who received SEL experienced greater improvements in NRS scores (mean change from BL of−3.12 vs−2.09 for SEL and PBO, respectively, p=.0004), PBC-40 itch domain scores (mean change from BL of−2.26 vs−1.37 for SEL and PBO, respectively, p=.0227), 5-D itch total scores (mean change from BL of−4.85 vs−2.30 for SEL and PBO, respectively, p<.0001), and 5-D itch degree domain scores (mean change from BL of−0.96 vs−0.54 for SEL and PBO, respectively, p=.0005). The overall safety profiles in pts with pruritus in the SEL and PBO groups were similar in this pooled analysis. Adverse events occurred in 58/76 (76%) SEL and PBO 40/50 (80%) PBO pts.

Conclusion: In agreement with previous studies, this pooled analysis indicates that up to 6 M of SEL treatment reduced pruritus to a greater extent vs PBO in pts with PBC who had moderate to severe pruritus when assessed across 3 different measures of itch. SEL was well tolerated in this pt population.