{
  "abstract": "Seladelpar is a first-in-class delpar (selective PPAR-delta agonist) indicated in the UK for the treatment of primary biliary cholangitis (PBC) including pruritus in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA. In two Phase 3, placebo-controlled trials (ENHANCE [ NCT03602560], RESPONSE [NCT04620733]), seladelpar significantly reduced pruritus in patients with moderate to severe pruritus at baseline (numerical rating scale [NRS] ≥4). Here, we present pooled pruritus outcomes across different measures of itch in patients with PBC with NRS ≥4 at baseline.Patients with PBC with an inadequate response or intolerance to UDCA were randomised 1:1:1 to daily, oral seladelpar 5 mg, seladelpar 10 mg, or placebo for 52 weeks in ENHANCE and 2:1 to daily, oral seladelpar 10 mg or placebo for 52 weeks in RESPONSE (ENHANCE terminated early with key endpoints amended to 3 months [M]). Pooled data from patients with NRS ≥4 at baseline who received seladelpar 10 mg or placebo in RESPONSE and at least 6M in ENHANCE were analysed. Changes across several measures of itch (NRS, PBC-40 itch domain, and 5-D itch scale) up to 6M were assessed.Of 126 patients with moderate to severe pruritus, 76 and 50 patients received seladelpar 10 mg or placebo, respectively, in RESPONSE and ENHANCE. Most patients at baseline were <50 years of age at PBC diagnosis (73/126; 58%) and had a history of pruritus (122/126; 97%) and fatigue (77/126; 61%). NRS, PBC-40 itch domain, and 5-D itch scale scores were similar between the seladelpar and placebo groups at baseline. At 6M, patients who received seladelpar experienced greater improvements in NRS scores (mean change from baseline [CFB] −3.12 [seladelpar] vs −2.09 [placebo], P = .0004), PBC-40 itch domain scores (mean CFB −2.26 [seladelpar] vs −1.37 [placebo], P = .0227), 5-D itch total scores (mean CFB −4.85 [seladelpar] vs −2.30 [placebo], P < .0001), and 5-D itch degree domain scores (mean CFB −0.96 [seladelpar] vs −0.54 [placebo], P = .0005). Overall, safety profiles in patients with pruritus in the seladelpar and placebo groups were similar. Adverse events occurred in 58/76 (76%) seladelpar patients and 40/50 (80%) placebo patients.Up to 6M of seladelpar treatment reduced pruritus to a greater extent than placebo in patients with PBC with moderate to severe pruritus when assessed across 3 different measures of itch. Seladelpar was well tolerated in this population.",
  "authors": [
    {
      "affiliations": [
        "Translational and Clinical Research Institute and Centre for Rare Disease, Newcastle University, Newcastle upon Tyne, UK"
      ],
      "name": "David EJ Jones"
    },
    {
      "affiliations": [
        "Division of Digestive Health and Liver Diseases, Miller School of Medicine, University of Miami, Miami, USA"
      ],
      "name": "Cynthia Levy"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland"
      ],
      "name": "Andreas E Kremer"
    },
    {
      "affiliations": [
        "Centro de Investigación y Gastroenterología, Hospital Angeles Clinica Londres, Mexico City, Mexico"
      ],
      "name": "Alma Ladron de Guevara Cetina"
    },
    {
      "affiliations": [
        "The Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina"
      ],
      "name": "Alejandra M Villamil"
    },
    {
      "affiliations": [
        "Department of Basic Medical Sciences, Faculty of Public Health in Bytom, Medical University of Silesia, Bytom, Poland"
      ],
      "name": "Ewa Janczewska"
    },
    {
      "affiliations": [
        "Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, USA"
      ],
      "name": "Mordechai Rabinovitz"
    },
    {
      "affiliations": [
        "Division of Internal Medicine, Università di Modena e Reggio Emilia, Modena, Italy"
      ],
      "name": "Pietro Andreone"
    },
    {
      "affiliations": [
        "Gilead Sciences, Inc., Foster City, USA"
      ],
      "name": "Leena Sathia"
    },
    {
      "affiliations": [
        "Gilead Sciences, Inc., Foster City, USA"
      ],
      "name": "Xin Qi"
    },
    {
      "affiliations": [
        "Gilead Sciences, Inc., Foster City, USA"
      ],
      "name": "Susheela Carroll"
    },
    {
      "affiliations": [
        "Gilead Sciences, Inc., Foster City, USA"
      ],
      "name": "Timothy R Watkins"
    },
    {
      "affiliations": [
        "Division of Digestive and Liver Diseases, University of Texas Southwestern, Dallas, USA"
      ],
      "name": "Marlyn J Mayo"
    }
  ],
  "title": "P35 Change in pruritus in patients with primary biliary cholangitis and moderate to severe pruritus: a pooled analysis from the RESPONSE and ENHANCE studies",
  "uid": "4936423c-b3ef-5e91-a882-b2736f98ec57"
}