Treatment strategies and survival of patients with connective tissue disease and pulmonary arterial hypertension: a COMPERA analysis

Oliver Distler¹, Christian Ofner¹, Dörte Huscher², Suzana Jordan¹, Silvia Ulrich³, Gerd Stähler⁴, Ekkehard Grünig⁵, Matthias Held⁶, H Ardeschir Ghofrani⁷, Martin Claussen⁸, Tobias J Lange⁹, Hans Klose¹⁰, Stephan Rosenkranz¹¹, Anton Vonk-Noordegraaf¹², C Dario Vizza¹³, Marion Delcroix¹⁴, Christian Opitz¹⁵, Christine Pausch¹⁶, Laura Scelsi¹⁷, Claus Neurohr¹⁸, Karen M Olsson^{19

20}, J Gerry Coghlan²¹, Michael Halank²², Dirk Skowasch²³, Jürgen Behr²⁴, Katrin Milger²⁴, Bjoern Andrew Remppis²⁵, Andris Skride²⁶, Elena Jureviciene²⁷, Lina Gumbiene²⁷, Skaidrius Miliauskas²⁸, Judith Löffler-Ragg²⁹, Heinrike Wilkens³⁰, David Pittrow^{16

31}, Marius M Hoeper^{19

20}, Ralf Ewert³²

Affiliations

¹ Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
² Institute of Biometry and Clinical Epidemiology, and Berlin Institute of Health, Charité-Universitätsmedizin, Corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany.
³ Department of Pulmonology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
⁴ Klinik für Pneumologie, Klinik Fachklinik Löwenstein, Löwenstein, Germany.
⁵ Center for Pulmonary Hypertension, Thoraxklinik at Heidelberg University Hospital, Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research, Heidelberg, Germany.
⁶ Department of Internal Medicine, Respiratory Medicine and Ventilatory Support, Medical Mission Hospital, Central Clinic Würzburg, Würzburg, Germany.
⁷ Department of Internal Medicine, Justus-Liebig-University Giessen, Universities of Giessen and Marburg Lung Center, Giessen, Germany.
⁸ Fachabteilung Pneumologie, LungenClinic Großhansdorf, Großhansdorf, Germany.
⁹ Department of Internal Medicine II, University Medical Center Regensburg, Regensburg, Germany.
¹⁰ Department of Respiratory Medicine, Eppendorf University Hospital, Hamburg, Germany.
¹¹ Clinic III for Internal Medicine (Cardiology) and Center for Molecular Medicine and the Cologne Cardiovascular Research Center, University of Cologne, Cologne, Germany.
¹² Department of Pulmonary Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.
¹³ Dipartimento di Scienze Cliniche Internistiche, Anestiologiche e Cardiolohiche, Sapienza, University of Rome, Rome, Italy.
¹⁴ Clinical Department of Respiratory Diseases, University Hospitals of Leuven and Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism, KU Leuven-University of Leuven, Leuven, Belgium.
¹⁵ Department of Cardiology, DRK Kliniken Berlin Westend, Berlin, Germany.
¹⁶ GWT-TUD GmbH, Innovation Center Real World Evidence, Dresden, Germany.
¹⁷ Fondazione IRCSS S. Matteo Pavia, Division of Cardiology Stolfo Davide, Azienda Sanitaria Universitaria Giuliano Isontina, Pavia, Italy.
¹⁸ Department of Pulmonology and Respiratory Medicine, Robert-Bosch-Krankenhaus Stuttgart, Stuttgart, Germany.
¹⁹ Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany.
²⁰ German Center of Lung Research, Gießen, Germany.
²¹ Department of Cardiology, Royal Free Hospital, London, UK.
²² Division of Pulmonology, Medical Department I, University Hospital Carl Gustav Carus of Technical University Dresden, Dresden, Germany.
²³ Innere Medizin-Kardiologie/Pneumologie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Bonn, Bonn, Germany.
²⁴ Department of Medicine V, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich, Member of the German Center for Lung Research, Munich, Germany.
²⁵ Herz- und Gefäßzentrum Bad Bevensen, Bad Bevensen, Germany.
²⁶ VSIA Pauls Stradins Clinical University Hospital, Riga, Lativa.
²⁷ Faculty of Medicine of Vilnius University, Competence Centre of Pulmonary Hypertension, Vilnius University Hospital Santaros klinikos, Vilnius, Lithuania.
²⁸ Department of Pulmonology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
²⁹ Department of Internal Medicine II, Medical University of Innsbruck, Innsbruck, Austria.
³⁰ Innere Medizin V, Universitätsklinikum des Saarlandes, Homburg, Germany.
³¹ Institute for Clinical Pharmacology, Medical Faculty, Technical University, Dresden, Germany.
³² Clinic of Internal Medicine, Department of Respiratory Medicine, Universitätsmedizin Greifswald, Germany.

PMID: 37462520
PMCID: PMC10986797
DOI: 10.1093/rheumatology/kead360

Treatment strategies and survival of patients with connective tissue disease and pulmonary arterial hypertension: a COMPERA analysis

Oliver Distler et al. Rheumatology (Oxford). 2024.

. 2024 Apr 2;63(4):1139-1146.

doi: 10.1093/rheumatology/kead360.

Authors

Affiliations

¹ Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
² Institute of Biometry and Clinical Epidemiology, and Berlin Institute of Health, Charité-Universitätsmedizin, Corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany.
³ Department of Pulmonology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
⁴ Klinik für Pneumologie, Klinik Fachklinik Löwenstein, Löwenstein, Germany.
⁵ Center for Pulmonary Hypertension, Thoraxklinik at Heidelberg University Hospital, Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research, Heidelberg, Germany.
⁶ Department of Internal Medicine, Respiratory Medicine and Ventilatory Support, Medical Mission Hospital, Central Clinic Würzburg, Würzburg, Germany.
⁷ Department of Internal Medicine, Justus-Liebig-University Giessen, Universities of Giessen and Marburg Lung Center, Giessen, Germany.
⁸ Fachabteilung Pneumologie, LungenClinic Großhansdorf, Großhansdorf, Germany.
⁹ Department of Internal Medicine II, University Medical Center Regensburg, Regensburg, Germany.
¹⁰ Department of Respiratory Medicine, Eppendorf University Hospital, Hamburg, Germany.
¹¹ Clinic III for Internal Medicine (Cardiology) and Center for Molecular Medicine and the Cologne Cardiovascular Research Center, University of Cologne, Cologne, Germany.
¹² Department of Pulmonary Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.
¹³ Dipartimento di Scienze Cliniche Internistiche, Anestiologiche e Cardiolohiche, Sapienza, University of Rome, Rome, Italy.
¹⁴ Clinical Department of Respiratory Diseases, University Hospitals of Leuven and Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism, KU Leuven-University of Leuven, Leuven, Belgium.
¹⁵ Department of Cardiology, DRK Kliniken Berlin Westend, Berlin, Germany.
¹⁶ GWT-TUD GmbH, Innovation Center Real World Evidence, Dresden, Germany.
¹⁷ Fondazione IRCSS S. Matteo Pavia, Division of Cardiology Stolfo Davide, Azienda Sanitaria Universitaria Giuliano Isontina, Pavia, Italy.
¹⁸ Department of Pulmonology and Respiratory Medicine, Robert-Bosch-Krankenhaus Stuttgart, Stuttgart, Germany.
¹⁹ Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany.
²⁰ German Center of Lung Research, Gießen, Germany.
²¹ Department of Cardiology, Royal Free Hospital, London, UK.
²² Division of Pulmonology, Medical Department I, University Hospital Carl Gustav Carus of Technical University Dresden, Dresden, Germany.
²³ Innere Medizin-Kardiologie/Pneumologie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Bonn, Bonn, Germany.
²⁴ Department of Medicine V, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich, Member of the German Center for Lung Research, Munich, Germany.
²⁵ Herz- und Gefäßzentrum Bad Bevensen, Bad Bevensen, Germany.
²⁶ VSIA Pauls Stradins Clinical University Hospital, Riga, Lativa.
²⁷ Faculty of Medicine of Vilnius University, Competence Centre of Pulmonary Hypertension, Vilnius University Hospital Santaros klinikos, Vilnius, Lithuania.
²⁸ Department of Pulmonology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
²⁹ Department of Internal Medicine II, Medical University of Innsbruck, Innsbruck, Austria.
³⁰ Innere Medizin V, Universitätsklinikum des Saarlandes, Homburg, Germany.
³¹ Institute for Clinical Pharmacology, Medical Faculty, Technical University, Dresden, Germany.
³² Clinic of Internal Medicine, Department of Respiratory Medicine, Universitätsmedizin Greifswald, Germany.

PMID: 37462520
PMCID: PMC10986797
DOI: 10.1093/rheumatology/kead360

Abstract

Objectives: Pulmonary arterial hypertension (PAH) occurs in various connective tissue diseases (CTDs). We sought to assess contemporary treatment patterns and survival of patients with various forms of CTD-PAH.

Methods: We analysed data from COMPERA, a European pulmonary hypertension registry, to describe treatment strategies and survival in patients with newly diagnosed PAH associated with SSc, SLE, MCTD, UCTD and other types of CTD. All-cause mortality was analysed according to the underlying CTD. For patients with SSc-PAH, we also assessed survival according to initial therapy with endothelin receptor antagonists (ERAs), phosphodiesterase type 5 inhibitors (PDE5is) or a combination of these two drug classes.

Results: This analysis included 607 patients with CTD-PAH. Survival estimates at 1, 3 and 5 years for SSc-PAH (n = 390) were 85%, 59% and 42%; for SLE-PAH (n = 34) they were 97%, 77% and 61%; for MCTD-PAH (n = 33) they were 97%, 70% and 59%; for UCTD-PAH (n = 60) they were 88%, 67% and 52%; and for other CTD-PAH (n = 90) they were 92%, 69% and 55%, respectively. After multivariable adjustment, the survival of patients with SSc-PAH was significantly worse compared with the other conditions (P = 0.001). In these patients, the survival estimates were significantly better with initial ERA-PDE5i combination therapy than with initial ERA or PDE5i monotherapy (P = 0.016 and P = 0.012, respectively).

Conclusions: Mortality remains high in patients with CTD-PAH, especially for patients with SSc-PAH. However, for patients with SSc-PAH, our results suggest that long-term survival may be improved with initial ERA-PDE5i combination therapy compared with initial monotherapy.

Keywords: connective tissue disease (CTD); endothelin receptor antagonists (ERA); phosphodiesterase type 5 inhibitor (PDE5i); pulmonary arterial hypertension; systemic sclerosis (SSc).

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Figures

**Figure 1.**
Flow chart of the selection process for the study cohort

**Figure 2.**
Kaplan–Meier survival estimates in various forms of CTD-PAH

**Figure 3.**
Kaplan–Meier survival estimates in patients with SSc-PAH according to the initial treatment regimen

See this image and copyright information in PMC

References

1. Thakkar V, Lau EM.. Connective tissue disease-related pulmonary arterial hypertension. Best Pract Res Clin Rheumatol 2016;30:22–38. - PubMed
1. Galie N, Humbert M, Vachiery JL. et al. 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: the Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J 2015;46:903–75. - PubMed
1. Steen VD, Medsger TA.. Changes in causes of death in systemic sclerosis, 1972–2002. Ann Rheum Dis 2007;66:940–4. - PMC - PubMed
1. Gurubhagavatula I, Palevsky HI.. Pulmonary hypertension in systemic autoimmune disease. Rheum Dis Clin North Am 1997;23:365–94. - PubMed
1. Callejas-Rubio JL, Moreno-Escobar E, de la Fuente PM. et al. Prevalence of exercise pulmonary arterial hypertension in scleroderma. J Rheumatol 2008;35:1812–6. - PubMed

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Treatment strategies and survival of patients with connective tissue disease and pulmonary arterial hypertension: a COMPERA analysis

Affiliations

Treatment strategies and survival of patients with connective tissue disease and pulmonary arterial hypertension: a COMPERA analysis

Authors

Affiliations

Abstract

Figures

References

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical