{
  "abstract": "Introduction Pruritus affects up to 80% of patients with primary biliary cholangitis (PBC) and significantly impairs quality of life. Seladelpar (SEL), a first-in-class delpar (selective PPAR-delta agonist), is approved for second-line treatment of PBC and has shown efficacy in improving cholestasis and pruritus in the pivotal, placebo (PBO)-controlled RESPONSE study ( NCT04620733). We report long-term pruritus outcomes from the RESPONSE study and interim results from its ongoing open-label extension study, ASSURE (NCT03301506), with confirmatory psychometric validation of the pruritus numeric rating scale (NRS).Methods In RESPONSE, pruritus NRS was collected daily for 6 months (M), then weekly for one week each month through 12M. Upon rollover to ASSURE, NRS was collected daily for 6M and then at scheduled clinic visits. Other measures included the 5-D Itch and PBC-40. Patients with moderate to severe pruritus (NRS ≥4) at baseline (MSPN) were analysed based on randomisation to SEL 10 mg or PBO in RESPONSE and reported as continuous or crossover SEL 10 mg groups in ASSURE. Regression analysis and Bland-Altman plots assessed agreement between single-visit and weekly averaged NRS scores. Robust psychometric validation of NRS included reliability, convergent validity, and meaningful within-patient change analyses. Change from baseline in NRS, 5-D Itch, and PBC-40 Itch domain scores were assessed in ASSURE with a data cutoff of Jan 31, 2025.Results Overall, there were 49 SEL and 23 PBO MSPN patients at baseline in RESPONSE. Among them, 33 SEL and 17 PBO patients rolled over to ASSURE, and 27 and 16 patients reached 30M. Daily NRS was strongly correlated with weekly NRS (r [95% CI], 0.93 [0.90, 0.95]). Validation of the NRS demonstrated it was valid and reliable. Reduction in pruritus with SEL in RESPONSE was maintained in ASSURE up to 30M, with clinically meaningful NRS improvement observed in ≥50% of patients upon SEL initiation for crossover patients in ASSURE from 15M through 30M. Mean (SE) 5-D Itch total and PBC-40 Itch domain scores were reduced from baseline in continuous SEL (−4.6 [0.7]; −3.3 [0.7]) and crossover SEL (−5.8 [1.1]; −4.3 [1.0]) patients.Conclusions SEL led to sustained, clinically meaningful improvement in pruritus among MSPN patients in RESPONSE and with up to 30 months of treatment. Additionally, repeated psychometric validation confirmed the reliability and validity of the NRS as an outcome measure of pruritus in PBC.",
  "authors": [
    {
      "affiliations": [
        "Gilead Sciences, Inc., Foster City, USA"
      ],
      "name": "Medical Scientist Christine Taylor"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, University Hospital Zürich, University of Zürich, Zürich, Switzerland"
      ],
      "name": "Andreas Kremer"
    },
    {
      "affiliations": [
        "Division of Digestive Health and Liver Diseases, Miller School of Medicine, University of Miami, Miami, USA"
      ],
      "name": "Cynthia Levy"
    },
    {
      "affiliations": [
        "Liver Institute Northwest, Seattle, USA"
      ],
      "name": "Kris Kowdley"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, USA"
      ],
      "name": "Hany Elbeshbeshy"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, Pusan National University and Biomedical Research Institute, Busan, Republic of Korea"
      ],
      "name": "Jeong Heo"
    },
    {
      "affiliations": [
        "Gilead Sciences, Inc., Foster City, USA"
      ],
      "name": "Kyung Min Kwon"
    },
    {
      "affiliations": [
        "Gilead Sciences, Inc., Foster City, USA"
      ],
      "name": "Jie Liu"
    },
    {
      "affiliations": [
        "Gilead Sciences, Inc., Foster City, USA"
      ],
      "name": "Caroline Burk"
    },
    {
      "affiliations": [
        "Gilead Sciences, Inc., Foster City, USA"
      ],
      "name": "Daria Crittenden"
    },
    {
      "affiliations": [
        "Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, USA"
      ],
      "name": "Marlyn Mayo"
    },
    {
      "affiliations": [
        "The Autoimmune and Rare Liver Disease Programme, Toronto General Hospital, Toronto, Canadal"
      ],
      "name": "Gideon Hirschfield"
    }
  ],
  "title": "P57 Improvements in moderate-to-severe pruritus patients with primary biliary cholangitis treated with seladelpar in up to 30 months of ASSURE",
  "uid": "97e2de6c-c627-5963-885c-850cfd11922b"
}