{
  "abstract": "Alagille syndrome (ALGS) and Progressive Familial lntrahepatic Cholestasis (PFIC) are rare cholestatic liver diseases (CLD) associated with severe pruritus along with markedly reduced health­ related quality of life (HRQoL). Maralixibat (MRX), an oral minimally absorbed ileal bile acid transporter (IBAT) inhibitor, is approved for the treatment of cholestatic pruritus in patients with ALGS ≥2 months of age and for the treatment of PFIC ≥3 months of age in the EU, respectively. This analysis assessed whether improvements in pruritus after MRX treatment are correlated with improvements in a variety of HRQoL domains in these CLD.The study designs of the Phase 2 randomized withdrawal period (RWD) ICONIC trial and Phase 3 randomized, double-blind, placebo-controlled (PBO) MARCH trial have been previously described. Separate retrospective analyses of pruritus and HRQoL data from the ICONIC trial in ALGS (18 weeks of open-label MRX treatment) and the MARCH trial in PFIC (26 weeks of MRX or PBO treatment) were conducted. Patients in both studies had to have moderate to severe pruritus as measured using a validated caregiver-reported Itch Reported Outcome (ltchRO) severity assessment tool (0=none to 4=very severe). HRQoL was assessed using the Pediatric Quality of Life Inventory Generic Core (PedsQL; 0–100 scale, 100=best quality of life), Physical Health (PH), Psychosocial Health (PSH), and Multidimensional Fatigue (MF) scale scores, which were collected via caregiver in both studies. In MARCH, a subset of questions from the exploratory diary questionnaire (EDQ) focused on sleep disturbance were assessed for their relationship to pruritus improvement. Spearman’s (r) coefficients were determined to evaluate the relationship between pruritus improvements and HRQoL.A total of 28 patients with ALGS from ICONIC were included with a mean± SD baseline age of 5.4 ± 4.2 years, ltchRO score of 2.9 ± 0.5, PedsQL score of 60.3 ± 16.6, PH score of 64.7 ± 20.0, PSH score of 57.6 ± 16.7, and MF score of 51.2 ± 22.6. After 18 weeks of open-label MRX treatment, there was a significant positive correlation between pruritus improvement and improvements in Peds QL (r 0.50 [p=0.007]), PSH (r 0.47 [p=0.012]), and MF (r 0.71 [p=0.0002]). In MARCH, 55 patients from the AII-PFIC cohort (29 MRX, 26 PBO) were included in the analysis with a mean± SD baseline age of 4.9 ± 4.1 years, ltchRO score of 2.9 ± 0.9, PedsQL score of 55.8 ± 19.0, PH score of 61.5 ± 22.4, PSH score of 52.0 ± 20.2, MF score of 57.8 ± 20.4 and EDQ sleep disturbance score of 3.7 ± 0.8. Among MRX-treated participants after 26 weeks of treatment, there was a significant positive correlation between pruritus improvement and improvements in Peds QL (r 0.53 [p=0.003]), PH (r 0.50 [p=0.006]), PSH (r 0.47 [p=0.01]), and sleep (r 0.96 [p<0.0001]). In the PBO-treated participants, improvements in pruritus were significantly correlated with improvements in PSH (r 0.41 [p=0.039]) and sleep (r 0.88 [p<0.0001]).These data further illustrate the robustness of MRX’s impact on the relationship between pruritus improvement and HRQoL across multiple domains. Irrespective of the CLD studied, improvements in pruritus after MRX treatment were strongly associated with improvements in HRQoL.",
  "authors": [
    {
      "affiliations": [
        "King’s College London, London, UK"
      ],
      "name": "Richard J Thompson"
    },
    {
      "affiliations": [
        "Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA"
      ],
      "name": "Alexander G Miethke"
    },
    {
      "affiliations": [
        "Service d’Hepatologie et de Transplantation Hepatique Pediatriques, Centre de Reference de l’Atresie des Voies Biliaires et des Cholestases Genetiques (AVB-CG), FSMR FILFOIE, ERN RARE LIVER, Hopital Bicetre, AP-HP, Faculte de Medecine Paris-Saclay, Le Kremlin-Bicetre, and lnserm U1193, Hepatinov, Universite Paris­Saclay, Orsay, France"
      ],
      "name": "Emmanuel Gonzales"
    },
    {
      "affiliations": [
        "The Children’s Hospital of Philadelphia, Philadelphia, PA, USA",
        "The Hospital for Sick Children, Toronto, ON, Canada"
      ],
      "name": "Binita M Kamath"
    },
    {
      "affiliations": [
        "Mirum Pharmaceuticals Inc, Foster City, CA, USA"
      ],
      "name": "Douglas B Mogul"
    },
    {
      "affiliations": [
        "Mirum Pharmaceuticals Inc, Foster City, CA, USA"
      ],
      "name": "Tiago Nunes"
    },
    {
      "affiliations": [
        "Mirum Pharmaceuticals Inc, Foster City, CA, USA"
      ],
      "name": "Jolan Terner-Rosenthal"
    },
    {
      "affiliations": [
        "Mirum Pharmaceuticals Inc, Foster City, CA, USA"
      ],
      "name": "Marshall Baek"
    },
    {
      "affiliations": [
        "Mirum Pharmaceuticals Inc, Foster City, CA, USA"
      ],
      "name": "Pamela Vig"
    },
    {
      "affiliations": [
        "Service d’Hepatologie et de Transplantation Hepatique Pediatriques, Centre de Reference de l’Atresie des Voies Biliaires et des Cholestases Genetiques (AVB-CG), FSMR FILFOIE, ERN RARE LIVER, Hopital Bicetre, AP-HP, Faculte de Medecine Paris-Saclay, Le Kremlin-Bicetre, and lnserm U1193, Hepatinov, Universite Paris­Saclay, Orsay, France"
      ],
      "name": "Emmanuel Jacquemin"
    }
  ],
  "title": "OC50 Improvements in pruritus after maralixibat treatment are associated with improved health-related quality of life for patients with cholestatic liver disease",
  "uid": "b2334204-c38f-579b-816f-aa3a2d3c6d3b"
}