{
  "abstract": "Introduction Pulmonary arterial hypertension (PAH) develops in 6–12% of systemic sclerosis (SSc) and is a major cause of morbidity and mortality. Current guidelines recommend risk-adapted therapy, with initial double-combination therapy for low-/intermediate-risk and triple therapy for high-risk patients. Most evidence derives from idiopathic PAH studies, whereas SSc-PAH patients have worse prognosis and less favourable treatment response. As such, robust long-term data in SSc-PAH are lacking. This gap is particularly evident in patients with milder haemodynamic impairment (mPAP 21-24 mmHg or PVR 2-3 WU), who remain at risk for adverse outcomes but lack evidence-based treatment guidance. We therefore aimed to evaluate the impact of initial therapy on mortality and PAH progression across haemodynamic thresholds and risk strata.Material and Methods We included incident, treatment-naïve SSc-PAH patients (2001–2021) from the EUSTAR database fulfilling the 2022 haemodynamic definition of PAH (EUSTAR Project CP122). Patients with severe ILD were excluded. Haemodynamics were classified as higher (mPAP >=25 mmHg, PVR >3 WU) or lower (mPAP 21-24 mmHg and/or PVR 2-3 WU). Risk was stratified using the 2022 ESC/ERS four-strata model. Initial therapy was PAH treatment within four months of diagnosis and continued >=3 months. Untreated patients served as comparators. Outcomes were all-cause mortality and PAH progression within 36 months, assessed by multivariable Cox regression adjusting for age, sex, DLCO, haemodynamics, and risk group.Results Of 301 patients, 170 (57%) received initial therapy (108 monotherapy, 62 combination); 131 (43%) were untreated. Treated patients had worse baseline haemodynamics and risk profiles ( table 1). Over a median 3.9 years (Q1–Q3: 1.6–6.3), 125 (42%) died. Among 227 patients with progression data, 85 (37%) progressed within 36 months (figure 1A). Adjusted analyses showed initial therapy was associated with reduced mortality and PAH progression, independent of haemodynamic thresholds and risk stratification (figure 1B and C). In the lower haemodynamic threshold group (n=83), 18 (22%) received initial therapy (16 monotherapy, 2 combination). Over 5.1 years (Q1–Q3: 2.5–7.9), 20 (24%) died. Adjusted for risk stratification, results suggested reduced mortality with initial therapy (HR 0.36, 95% CI 0.08–1.67), though not statistically significant (figure 1D).Conclusions Initial therapy was associated with improved survival and reduced PAH progression in SSc-PAH, with consistent effects across haemodynamic thresholds and risk strata. These findings support guideline-recommended early intervention, highlight the importance of high-quality observational data in rare diseases, and underscore the need for RCTs to clarify treatment effects in patients with milder haemodynamic impairment.Abstract OC.03 Figure 1Abstract OC.03 Table 1Comparison of base line characteristics of treated patients and the untreated comparator group",
  "authors": [
    {
      "affiliations": [
        "Department of Rheumatology, Hospital of Southern Norway, Kristiansand, Norway",
        "Institute of Clinical Medicine, University of Oslo, Oslo, Norway"
      ],
      "name": "Hilde Jenssen Bjørkekjær"
    },
    {
      "affiliations": [
        "Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland",
        "Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy"
      ],
      "name": "Cosimo Bruni"
    },
    {
      "affiliations": [
        "Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway",
        "Institute for Experimental Medical Research, KG Jebsen center, University of Oslo, Norway"
      ],
      "name": "Kaspar Broch"
    },
    {
      "affiliations": [
        "Institute of Clinical Medicine, University of Oslo, Oslo, Norway",
        "Oslo Centre for Biostatistics and Epidemiology, Research Support Services, Oslo University Hospital - Rikshospitalet, Oslo, Norway"
      ],
      "name": "Cathrine Brunborg"
    },
    {
      "affiliations": [
        "Department of Rheumatology, 12 de Octubre University Hospital, Madrid, Spain"
      ],
      "name": "Patricia E Carreira"
    },
    {
      "affiliations": [
        "UOC Reumatologia ed Immunologia Clinica, 9 Spedali Civili di Brescia, Scleroderma UNIT, Piazzale Spedali Civili 1, 25123 Brescia, Italy"
      ],
      "name": "Paolo Airò"
    },
    {
      "affiliations": [
        "Systemic Autoimmune Diseases Unit. Department of Internal Medicine, University Vall d’Hebron Hospital, Barcelona, Spain"
      ],
      "name": "Carmen Pilar Simeón-Aznar"
    },
    {
      "affiliations": [
        "Rheumatology Department, Bordeaux University Hospital, Bordeaux, France"
      ],
      "name": "Marie-Elise Truchetet"
    },
    {
      "affiliations": [
        "Rheumatology Section, Department of Medicine, University of Verona, Verona, Italy",
        "Division of Rheumatology, Department of Medicine - DIMED, University and Hospital of Padua, Padova, Italy"
      ],
      "name": "Alessandro Giollo"
    },
    {
      "affiliations": [
        "Rheumatology Institute, Rambam Health Care Campus, Rappaport Faculty of Medicine, Technion-Institute of Technology, Haifa, Israel"
      ],
      "name": "Alexandra Balbir-Gurman"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, Poitiers University Hospital, Poitiers, France"
      ],
      "name": "Mickael Martin"
    },
    {
      "affiliations": [
        "Centre for Rheumatology and Connective Tissue Diseases, University College London Division of Medicine and Royal Free Hospital, London, United Kingdom"
      ],
      "name": "Christopher P Denton"
    },
    {
      "affiliations": [
        "Fondazione di Medicina Molecolare e Terapia Cellulare, Università Politecnica delle Marche, Ancona, Italy",
        "Hiller Research Center, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University, Düsseldorf, Germany"
      ],
      "name": "Armando Gabrielli"
    },
    {
      "affiliations": [
        "Leeds Institute of Rheumatic and Musculoskeletal Medicine, LIRMM, Leeds, UK",
        "NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals Trust, Leeds, UK"
      ],
      "name": "Francesco Del Galdo"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Radboud Universiteit, Nijmegen, Netherlands"
      ],
      "name": "Madelon C Vonk"
    },
    {
      "affiliations": [
        "Institute of Clinical Medicine, University of Oslo, Oslo, Norway",
        "Lillehammer Hospital for Rheumatic Diseases, Lillehammer, Norway"
      ],
      "name": "Håvard Fretheim"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Hospital of Southern Norway, Kristiansand, Norway"
      ],
      "name": "Helle Bitter"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Oslo University Hospital, Rikshospitalet, Oslo, Norway"
      ],
      "name": "Øyvind Midtvedt"
    },
    {
      "affiliations": [
        "Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway"
      ],
      "name": "Arne Andreassen"
    },
    {
      "affiliations": [
        "Institute of Clinical Medicine, University of Oslo, Oslo, Norway",
        "Department of Cardiology, Hospital of Southern Norway, Arendal, Norway"
      ],
      "name": "Sverre Høie"
    },
    {
      "affiliations": [
        "First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan"
      ],
      "name": "Yoshiya Tanaka"
    },
    {
      "affiliations": [
        "Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany"
      ],
      "name": "Gabriela Riemekasten"
    },
    {
      "affiliations": [
        "Dept of Rheumatology and Clinical Immunology, Justus-Liebig University Giessen, Campus Kerckhoff, Bad Nauheim, Germany"
      ],
      "name": "Ulf Müller-Ladner"
    },
    {
      "affiliations": [
        "Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), & Inflammation, fibrosis and ageing initiative (INFLAGE), IRCCS San Raffaele Hospital, Milan, Italy",
        "University Vita Salute San Raffaele, Milan, Italy"
      ],
      "name": "Marco Matucci-Cerinic"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain"
      ],
      "name": "Ivan Castellví"
    },
    {
      "affiliations": [
        "Rheumatology, Charite University Hospital, Berlin, Germany"
      ],
      "name": "Elise Siegert"
    },
    {
      "affiliations": [
        "Department of Internal Medicine and Clinical Immunology, Referral Centre for Centre for rare systemic autoimmune diseases North of France, North-West, Mediterranean and Guadeloupe (CeRAINOM), CHU Lille, Univ. Lille, Inserm, U1286",
        "INFINITE - Institute for Translational Research in Inflammation, F-59000 Lille, France."
      ],
      "name": "Eric Hachulla"
    },
    {
      "affiliations": [
        "Institute of Clinical Medicine, University of Oslo, Oslo, Norway",
        "Department of Rheumatology, Oslo University Hospital, Rikshospitalet, Oslo, Norway"
      ],
      "name": "Øyvind Molberg"
    },
    {
      "affiliations": [
        "Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland"
      ],
      "name": "Oliver Distler"
    },
    {
      "affiliations": [
        "Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland",
        "Department of Rheumatology, Oslo University Hospital, Rikshospitalet, Oslo, Norway"
      ],
      "name": "Anna-Maria Hoffmann-Vold"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Hospital of Southern Norway, Kristiansand, Norway",
        "Institute of Clinical Medicine, University of Oslo, Oslo, Norway",
        "Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland",
        "Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy",
        "Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway",
        "Institute for Experimental Medical Research, KG Jebsen center, University of Oslo, Norway",
        "Oslo Centre for Biostatistics and Epidemiology, Research Support Services, Oslo University Hospital - Rikshospitalet, Oslo, Norway",
        "Department of Rheumatology, 12 de Octubre University Hospital, Madrid, Spain",
        "UOC Reumatologia ed Immunologia Clinica, 9 Spedali Civili di Brescia, Scleroderma UNIT, Piazzale Spedali Civili 1, 25123 Brescia, Italy",
        "Systemic Autoimmune Diseases Unit. Department of Internal Medicine, University Vall d’Hebron Hospital, Barcelona, Spain",
        "Rheumatology Department, Bordeaux University Hospital, Bordeaux, France",
        "Rheumatology Section, Department of Medicine, University of Verona, Verona, Italy",
        "Division of Rheumatology, Department of Medicine - DIMED, University and Hospital of Padua, Padova, Italy",
        "Rheumatology Institute, Rambam Health Care Campus, Rappaport Faculty of Medicine, Technion-Institute of Technology, Haifa, Israel",
        "Department of Internal Medicine, Poitiers University Hospital, Poitiers, France",
        "Centre for Rheumatology and Connective Tissue Diseases, University College London Division of Medicine and Royal Free Hospital, London, United Kingdom",
        "Fondazione di Medicina Molecolare e Terapia Cellulare, Università Politecnica delle Marche, Ancona, Italy",
        "Hiller Research Center, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University, Düsseldorf, Germany",
        "Leeds Institute of Rheumatic and Musculoskeletal Medicine, LIRMM, Leeds, UK",
        "NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals Trust, Leeds, UK",
        "Department of Rheumatology, Radboud Universiteit, Nijmegen, Netherlands",
        "Lillehammer Hospital for Rheumatic Diseases, Lillehammer, Norway",
        "Department of Rheumatology, Oslo University Hospital, Rikshospitalet, Oslo, Norway",
        "Department of Cardiology, Hospital of Southern Norway, Arendal, Norway",
        "First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan",
        "Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany",
        "Dept of Rheumatology and Clinical Immunology, Justus-Liebig University Giessen, Campus Kerckhoff, Bad Nauheim, Germany",
        "Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), & Inflammation, fibrosis and ageing initiative (INFLAGE), IRCCS San Raffaele Hospital, Milan, Italy",
        "University Vita Salute San Raffaele, Milan, Italy",
        "Department of Rheumatology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain",
        "Rheumatology, Charite University Hospital, Berlin, Germany",
        "Department of Internal Medicine and Clinical Immunology, Referral Centre for Centre for rare systemic autoimmune diseases North of France, North-West, Mediterranean and Guadeloupe (CeRAINOM), CHU Lille, Univ. Lille, Inserm, U1286",
        "INFINITE - Institute for Translational Research in Inflammation, F-59000 Lille, France."
      ],
      "name": "on behalf of the EUSTAR collaborators"
    }
  ],
  "title": "OC.03 Initial therapy in SSC-PAH improves outcomes across haemodynamic thresholds and risk stratification: insights from the EUSTAR database",
  "uid": "f393062a-6bb6-53fd-936a-7bbb4901a8ba"
}