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Publications

Journal Article Ahead of print

PubMed: 42876376 DOI: 10.1002/art.70372

Initial treatment strategies and outcomes across haemodynamic thresholds and risk stratification in incident systemic sclerosis-associated pulmonary arterial hypertension: a EUSTAR analysis.

Arthritis Rheumatol

Authors: Hilde Jenssen Bjørkekjær, Cosimo Bruni, Kaspar Broch, Cathrine Brunborg, Patricia E Carreira, Paolo Airò, Carmen Pilar Simeón-Aznar, Marie-Elise Truchetet, Alessandro Giollo, Alexandra Balbir-Gurman, Mickael Martin, Christopher P Denton, Armando Gabrielli, Francesco Del Galdo, Madelon C Vonk, Håvard Fretheim, Helle Bitter, Øyvind Midtvedt, Arne K Andreassen, Sverre Høie, Yoshiya Tanaka, Gabriela Riemekasten, Ulf Müller-Ladner, Marco Matucci-Cerinic, Ivan Castellví, Elise Siegert, Eric Hachulla, Øyvind Molberg, Oliver Distler, 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, 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 Unit, Department of Medicine, University of Verona, Verona, Italy.
  • Rheumatology Unit, 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.
  • ProCardio Center for Innovation, Clinic of Heart-, Lung- and Vascular Diseases, Oslo University Hospital, Rikshospitalet, Oslo, 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.
  • Inflammation Fibrosis and Ageing Initiative (INFLAGE), Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
  • Department of Rheumatology, Institut de Recerca Sant Pau (IR Sant Pau), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
  • Rheumatology, Charité University Hospital, Berlin, Germany.
  • Department of Internal Medicine and Clinical Immunology, Referral Centre for rare systemic autoimmune diseases North of France, North-West, Mediterranean and Guadeloupe (CeRAINOM), CHU Lille, Univ. Lille, Inserm, U1286, France.
  • INFINITE - Institute for Translational Research in Inflammation, F-59000, Lille, France.

Abstract

OBJECTIVE

Real-world initial treatment strategies in SSc-PAH remain incompletely described. We aimed to characterise these strategies across haemodynamic thresholds and risk strata and evaluate outcome associations.

METHODS

We analysed treatment-naïve SSc-PAH patients in EUSTAR (2000-2021) fulfilling the 2022 haemodynamic definition. Initial therapy comprised treatment initiated within 4 months of RHC. As-treated (AT) analyses were primary and intention-to-treat (ITT) analyses supportive. Outcomes were all-cause mortality and 36-month PAH progression.

RESULTS

Among 301 patients, 198 (66%) initiated therapy and 170 maintained therapy for ≥3 months. Therapy was initiated in 31% with milder haemodynamic impairment (mPAP 21-24 mmHg and/or PVR 2-3 WU) versus 79% fulfilling the previous haemodynamic definition; combination therapy increased from 14% to 67% across low- to high-risk strata. Over a median 3.9 years, 125 (42%) died and 85/227 (37%) progressed. Adjusted ITT analyses showed no association with either outcome, whereas adjusted AT analyses showed lower mortality risk with sustained monotherapy and combination therapy (HR 0.50, 95% CI 0.27-0.92 and HR 0.40, 95% CI 0.18-0.88, respectively) and lower PAH progression risk with sustained initial therapy (HR 0.37, 95% CI 0.18-0.76). In the milder haemodynamic subgroup, the mortality estimate was directionally consistent but imprecise.

CONCLUSION

Initial treatment strategies reflected haemodynamic severity and baseline risk, while variation suggested potential implementation gaps. Sustained initial therapy was associated with lower risks of mortality and PAH progression. Contrasting ITT and AT estimates highlight challenges in observational treatment-outcome comparisons. Findings in the milder haemodynamic subgroup support dedicated prospective studies.

MeSH

Sclerosis, Hypertension, Mortality, Arthritis, Pulmonary Arterial Hypertension, Therapeutics, Scleroderma, Systemic