{
  "abstract": "Systemic sclerosis (SSc) is a rare, heterogeneous, systemic autoimmune rheumatic disease characterised by vasculopathy, immune dysregulation and fibrosis affecting multiple organ systems. The complexity and variability of SSc manifestations pose significant challenges for clinical trial design and endpoint selection. Historically, three types of trial concepts have emerged: studies focused on a single organ; studies suggesting disease modification by combining a primary single-organ endpoint with supportive secondary endpoints across other systems, and studies explicitly designed to demonstrate disease modification through combined endpoints.This expert review explores the current landscape and future directions of clinical endpoints in SSc trials. It highlights the growing importance of patient-reported outcomes, such as the Health Assessment Questionnaire-Disability Index and ScleroID, which provide valuable insights into patient experiences. The review also discusses the emergence of candidate composite endpoints, including the revised Composite Response Index in Systemic Sclerosis, which integrates clinical, functional and patient-centred measures to better reflect treatment efficacy.Despite progress, significant unmet needs remain. Many endpoints assess damage at advanced stages, underscoring the need for earlier indicators of disease progression. The review advocates for incorporating time-to-event analyses, imaging and biomarker-based assessments to enhance sensitivity and relevance. It also emphasises the importance of refining composite endpoints to include continuous measures and broader domains such as vascular and gastrointestinal involvement. These efforts aim to improve the design and interpretability of SSc clinical trials, ultimately enhancing therapeutic development and patient outcomes.",
  "authors": [
    {
      "affiliations": [
        "Department of Rheumatology, Oslo University Hospital, Oslo, Norway",
        "Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland"
      ],
      "name": "Anna-Maria Hoffmann-Vold"
    },
    {
      "affiliations": [
        "Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland"
      ],
      "name": "Oliver Distler"
    },
    {
      "affiliations": [
        "Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and Biomedical Research Centre, Leeds Teaching Hospital Trusts, Leeds, UK"
      ],
      "name": "Francesco Del Galdo"
    },
    {
      "affiliations": [
        "Department of Rheumatology, University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany",
        "Hiller Research Center, University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany"
      ],
      "name": "Jörg HW Distler"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Cochin Hospital, Université Paris Cité, INSERM U1016, Paris, France"
      ],
      "name": "Yannick Allanore"
    },
    {
      "affiliations": [
        "Division of Rheumatology and Clinical Immunology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York, USA"
      ],
      "name": "Elana J Bernstein"
    },
    {
      "affiliations": [
        "Division of Medicine, University College London, London, UK"
      ],
      "name": "Christopher P Denton"
    },
    {
      "affiliations": [
        "Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan"
      ],
      "name": "Masataka Kuwana"
    },
    {
      "affiliations": [
        "Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS Ospedale San Raffaele Scientific Institute, Milan, Italy",
        "Vita-Salute San Raffaele University, Milan, Italy",
        "Inflammation Fibrosis and Ageing Initiative (INFLAGE), Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy"
      ],
      "name": "Marco Matucci-Cerinic"
    },
    {
      "affiliations": [
        "TA Inflammation Med, Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany"
      ],
      "name": "Margarida Alves"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Ghent University Hospital, Ghent, Belgium",
        "Department of Internal Medicine, Ghent University, Ghent, Belgium",
        "Unit for Molecular Immunology and Inflammation, VIB Inflammation Research Centre, Ghent, Belgium"
      ],
      "name": "Vanessa Smith"
    }
  ],
  "title": "Expert viewpoint on endpoints in systemic sclerosis: current and future outlook",
  "uid": "ae525c9d-4775-546a-b6f7-df8e9c69fa32"
}