{
  "abstract": "Background Progressive familial intrahepatic cholestasis (PFIC) comprises a heterogeneous group of disorders linked to genetic defects in hepatocanalicular transporters. Prior data has demonstrated total bilirubin (TB) is associated with improved transplant-free survival in this disorder. Maralixibat, an IBAT inhibitor, is approved in the US for the treatment of cholestatic pruritus in individuals ≥12 months old with PFIC, has been shown to reduce TB. Here, we evaluate the relationship between pruritus response and changes in TB in MARCH and MARCH-ON.Methods MARCH/MARCH-ON have been previously described. Changes in TB were evaluated during the first 26 weeks of MRX treatment (average of weeks 18, 22, and 26). Pruritus was assessed with average morning ItchRO(Obs)severity score in week 15-26 and response was defined as ≥1-point reduction from baseline or having the average score ≤ 1 point. Differences between pruritus responders and non-responders were analyzed using Wilcoxon signed-rank test and Fisher’s exact test.Results Fifty-nine children were treated with MRX [PFIC1: n=12 (20%); nt-PFIC2: n=28 (47%); PFIC3: n=9 (15%); PFIC4: n=7 (12%); PFIC6: n=3 (5%)]. Pruritus response was observed in 37 (63%). Pruritus responders had lower Baseline TB compared to non-responders (52 vs. 107 µmol/L, p=0.006) and had greater reductions in TB following treatment (-23.9 vs. -9.7 µmol/L, p=0.048). Normalization of TB occurred more frequently in pruritus responders (p<0.01).Conclusions Changes in bilirubin and pruritus are linked in patients on MRX with greater reductions in bilirubin, an important marker of liver health, being observed in pruritus responders. People treated earlier in the course of disease (i.e., lower bilirubin) may have greater likelihood of improvement in pruritus.",
  "authors": [
    {
      "affiliations": [
        "Institute of Liver Studies, King’s College London, London, United Kingdom"
      ],
      "name": "Richard Thompson"
    },
    {
      "affiliations": [
        "Pediatric Hepatology, Gastroenterology and Transplantation, ASST Papa Giovanni XXIII, Bergamo, Italy"
      ],
      "name": "Lorenzo D’Antiga"
    },
    {
      "affiliations": [
        "New York University Grossman School of Medicine, New York, New York, United States of America"
      ],
      "name": "Nadia Ovchinsky"
    },
    {
      "affiliations": [
        "Children’s Hospital Los Angeles, Los Angeles, California, United States of America"
      ],
      "name": "Chuan-Hao Lin"
    },
    {
      "affiliations": [
        "Mirum Pharmaceuticals, Inc., Foster City, California, United States of America"
      ],
      "name": "Douglas Mogul"
    },
    {
      "affiliations": [
        "Mirum Pharmaceuticals, Inc., Foster City, California, United States of America"
      ],
      "name": "Tiago Nunes"
    },
    {
      "affiliations": [
        "Mirum Pharmaceuticals, Inc., Foster City, California, United States of America"
      ],
      "name": "Shannon Vandriel"
    },
    {
      "affiliations": [
        "Mirum Pharmaceuticals, Inc., Foster City, California, United States of America"
      ],
      "name": "Cheng Chen"
    },
    {
      "affiliations": [
        "Mirum Pharmaceuticals, Inc., Foster City, California, United States of America"
      ],
      "name": "Pamela Vig"
    },
    {
      "affiliations": [
        "Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America"
      ],
      "name": "Alexander Miethke"
    },
    {
      "affiliations": [
        "Mirum Pharmaceuticals, Inc., Foster City, California, United States of America"
      ],
      "name": "Jolan Terner-Rosenthal"
    }
  ],
  "title": "OC32 Greater improvements in bilirubin were observed in pruritus responders after maralixibat treatment in patients with PFIC: data from the MARCH/MARCH-ON trials",
  "uid": "861f8b28-37ff-5a9a-afbc-5f9ac9f58ac4"
}