{
  "abstract": "Fatigue and pruritus are common symptoms in PBC. In the phase III ELATIVE® trial ( NCT04526665), elafibranor significantly improved biomarkers of cholestasis in PBC. Here, we report the impact of elafibranor vs placebo on fatigue, and the association between fatigue and pruritus.Patients with PBC were randomized 2:1 to elafibranor 80 mg (n=108) or placebo (n=53). Fatigue was assessed via the Patient-Reported Outcome Measurement Information System Fatigue Short Form 7a (PFSF 7a) and PBC-40 Fatigue domain. Data are reported for patients with moderate-to-severe fatigue at baseline (PFSF 7a score ≥60; PBC-40 Fatigue domain score ≥29). Changes to Week 52 were summarized as categorical changes, percentage changes, and minimal clinically important differences (MCIDs; PFSF 7a: ≥3; PBC-40 Fatigue domain: ≥5). Spearman’s correlation coefficients were calculated between fatigue (PFSF 7a and PBC-40 Fatigue domain) and pruritus (5-D Itch and PBC-40 Itch domain) patient-reported outcomes (PROs) for scores at baseline and change from baseline to Week 52. Patients with missing data at baseline and/or Week 52 were excluded.For PFSF 7a, 42/95 (44.2%) patients receiving elafibranor and 16/46 (34.8%) receiving placebo had moderate-to-severe fatigue at baseline. By Week 52, 18/42 (42.9%) patients receiving elafibranor vs 5/16 (31.3%) receiving placebo improved to mild/normal fatigue. Mean (95% CI) percentage change in PFSF 7a score was greater with elafibranor (−9.5% [−12.9%, −6.2%]) vs placebo (−4.2% [−9.6%, 1.2%]). Patients with an improvement ≥MCID at Week 52: elafibranor, n=28/42 (66.7%); placebo, n=5/16 (31.3%). For the PBC-40 Fatigue domain, 53/95 (55.8%) patients receiving elafibranor and 26/46 (56.5%) receiving placebo had moderate-to-severe fatigue at baseline. By Week 52, 12/53 (22.6%) patients receiving elafibranor vs 4/26 (15.4%) receiving placebo improved to mild/no fatigue. Mean (95% CI) percentage change in PBC-40 Fatigue domain score was greater with elafibranor (−9.8% [−15.4%, −4.1%]) vs placebo (−5.8% [−12.0%, 0.4%]). Patients with an improvement ≥MCID at Week 52: elafibranor, n=21/53 (39.6%); placebo, n=7/26 (26.9%). At baseline, fatigue and pruritus PRO scores had a weak correlation (r=0.25–0.35), suggesting pruritus was not a main driver of fatigue. Similarly, changes in fatigue and pruritus PROs from baseline to Week 52 did not demonstrate a strong correlation (r=0.26–0.33), and they could improve independently of one another.Elafibranor resulted in clinically meaningful improvements in fatigue, with greater improvements vs placebo. A weak correlation between fatigue and pruritus PROs at baseline, and in improvements over time, suggests that elafibranor can improve these debilitating PBC symptoms independently of each other.",
  "authors": [
    {
      "affiliations": [
        "Translational and Clinical Research Institute and NIHR Newcastle Biomedical Research Center, Newcastle University, Newcastle Upon Tyne, UK, Newcastle Upon Tyne, UK"
      ],
      "name": "David E Jones"
    },
    {
      "affiliations": [
        "Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy, Milan, Italy"
      ],
      "name": "Marco Carbone"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland, Zurich, Switzerland"
      ],
      "name": "Andreas E Kremer"
    },
    {
      "affiliations": [
        "Schiff Center for Liver Diseases, University of Miami, Miami, FL, USA, Miami, USA",
        "Division of Digestive Health and Liver Diseases, University of Miami School of Medicine, Miami, FL, USA, Miami, USA"
      ],
      "name": "Cynthia Levy"
    },
    {
      "affiliations": [
        "Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA, Dallas, USA"
      ],
      "name": "Marlyn J Mayo"
    },
    {
      "affiliations": [
        "Department of Internal Medicine II, Saarland University Medical Center, Homburg, Germany, Homburg, Germany"
      ],
      "name": "Jörn M Schattenberg"
    },
    {
      "affiliations": [
        "Ipsen, Cambridge, MA, USA, Cambridge, USA"
      ],
      "name": "Nuno Antunes"
    },
    {
      "affiliations": [
        "Ipsen, London, UK, London, UK"
      ],
      "name": "Darren Asquith"
    },
    {
      "affiliations": [
        "Ipsen, Paris, France, Paris, France"
      ],
      "name": "Hugo Gomes da Silva"
    },
    {
      "affiliations": [
        "Ipsen, Zug, Switzerland, Zug, Switzerland"
      ],
      "name": "Mickael Lothgren"
    },
    {
      "affiliations": [
        "Ipsen, Paris, France, Paris, France"
      ],
      "name": "Marwan Sleiman"
    },
    {
      "affiliations": [
        "Ipsen, Paris, France, Paris, France"
      ],
      "name": "Nathan Touati"
    },
    {
      "affiliations": [
        "Ipsen, London, UK, London, UK"
      ],
      "name": "Lesley Tranter"
    },
    {
      "affiliations": [
        "Liver Unit, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada, Calgary, Canada"
      ],
      "name": "Mark Swain"
    }
  ],
  "title": "P26 Elafibranor improves fatigue versus placebo in patients with primary biliary cholangitis (PBC), with limited correlation with pruritus: analyses from the phase III ELATIVE® trial",
  "uid": "b8b433ff-be47-54a4-95ac-3ca59ec438f6"
}