Temporal trends in vascular medication use in 8,079 patients with systemic sclerosis: insights to inform future trials and therapeutic strategies from the EUSTAR cohort

Stefano Di Donato; John D Pauling; Sheila Ramjug; Yannick Allanore; Edward B Jude; Marie-Elise Truchetet; Paolo Airò; Lidia P Ananyeva; Andra Balanescu; Gonçalo Boleto; Francesco Paolo Cantatore; Patricia E Carreira; Carolina de Souza Müller; Masataka Kuwana; Gianluca Moroncini; Marco Di Battista; Luc Mouthon; Madelon C Vonk; Elisabetta Zanatta; Marco- Matucci-Cerinic; Francesco Del Galdo; Michael Hughes

doi:10.1093/rheumatology/keaf290

Temporal trends in vascular medication use in 8,079 patients with systemic sclerosis: insights to inform future trials and therapeutic strategies from the EUSTAR cohort

Rheumatology (Oxford). 2025 Jun 3:keaf290. doi: 10.1093/rheumatology/keaf290. Online ahead of print.

Authors

Stefano Di Donato^{1

2

3}, John D Pauling⁴, Sheila Ramjug⁵, Yannick Allanore⁶, Edward B Jude⁷, Marie-Elise Truchetet^{3

8}, Paolo Airò⁹, Lidia P Ananyeva¹⁰, Andra Balanescu¹¹, Gonçalo Boleto^{12

13}, Francesco Paolo Cantatore¹⁴, Patricia E Carreira¹⁵, Carolina de Souza Müller¹⁶, Masataka Kuwana¹⁷, Gianluca Moroncini^{18

19}, Marco Di Battista²⁰, Luc Mouthon²¹, Madelon C Vonk²², Elisabetta Zanatta^{23

24}, Marco- Matucci-Cerinic^{25

26}, Francesco Del Galdo^{1

2}, Michael Hughes^{5

27}

Affiliations

¹ Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
² NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals Trust, Leeds, UK.
³ Univ. Bordeaux, CNRS, ImmunoConcEpT, UMR 5164, Bordeaux, Nouvelle-Aquitaine, France.
⁴ Department of Rheumatology, North Bristol NHS Trust Southmead Hospital, Bristol, UK.
⁵ Northern Care Alliance NHS Foundation Trust, Salford Care Organisation, Salford, UK.
⁶ Department of Rheumatology, Cochin Hospital, APHP, Université Paris Cité, Paris, France.
⁷ Tameside and Glossop Integrated Care NHS Foundation Trust, Ashton-under-Lyne, UK and Department of Diabetes, Endocrinology and Gastroenterology, University of Manchester, Manchester, UK.
⁸ CHU de Bordeaux, Rheumatology department, Centre National de référence Des Maladies Autoimmunes et Systémiques Rares Est/Sud-Ouest (RESO), Bordeaux, Nouvelle-Aquitaine, France.
⁹ Scleroderma Unit, Division of Rheumatology and Clinical Immunology, ASST Spedali Civili, Brescia, Italy.
¹⁰ V.A. Nasonova Rersearch Institute of Rheumatology, Moscow, Russian Federation.
¹¹ Sf Maria Hospital, University of Medicine and Pharmacy Carol Davila, Bucharest, Romania.
¹² Rheumatology Department, Unidade Local de Saúde Santa Maria, Centro Académico de Medicina de Lisboa, Lisboa, Portugal.
¹³ Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Centro Académico de Medicina de Lisboa, Lisboa, Portugal.
¹⁴ Rheumatology Clinic-Department of Medical and Surgical Sciences, University of Foggia, Italy.
¹⁵ Rheumatology Department, University Hospital 12 de Octubre and Complutense University, Madrid, Spain.
¹⁶ Division of Rheumatology, Department of Medicine, Universidade Federal do Paraná, Curitiba, Brazil.
¹⁷ Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan.
¹⁸ Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona, Italy.
¹⁹ Clinica Medica, Department of Internal Medicine, Marche University Hospital, Ancona, Italy.
²⁰ Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa.
²¹ Department of Internal Medicine, Cochin Hospital, APHP, Université Paris Cité, Paris, France.
²² Department of Rheumatology, Radboud University Njmegen Medical Center, Nijmegen, the Netherlands.
²³ Department of Medicine, University of Padova, Padova, Italy.
²⁴ Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy.
²⁵ IRCCS San Raffaele Hospital, Unit of Immunology, Rheumatology, Allergy and Rare diseases (UnIRAR), Milan, Italy.
²⁶ Vita Salute San Raffaele University, Milano, Italy.
²⁷ Division of Musculoskeletal and Dermatological Sciences, Faculty of Biology, Medicine and Health, Centre for Musculoskeletal Research, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.

PMID: 40457784
DOI: 10.1093/rheumatology/keaf290

Abstract

Objectives: Systemic sclerosis (SSc) is characterised by widespread vascular damage resulting in digital and systemic vasculopathic sequelae. Although there are effective treatments available, vascular disease remains a significant cause of morbidity and mortality in SSc. Our aim was to describe patterns of vascular medication use in SSc, including examination for potential changes over time.

Methods: A cross-sectional study of SSc patients enrolled in the EUSTAR database meeting 2013 ACR/EULAR SSc criteria. Patients were divided into two time periods: 2012-2017 and 2018-2022. We analysed the prescription patterns of endothelin receptor antagonists (ERA), phosphodiesterase type-5 inhibitors (PDE5i), calcium channel blockers (CCB), intravenous iloprost, and antiplatelet therapies. Logistic regression was used to evaluate temporal trends and interaction effects.

Results: 8079 patients were included. Significant increases over time were observed in the use of ERA (7% to 12%, p< 0.001), PDE5i (5.4% to 7.2%, p= 0.064), CCB (20% to 32%, p< 0.001), and anti-platelet therapies (15% to 20%, p< 0.001). There was a notable decrease in iloprost use (3.1% to 0.3%, p< 0.001). The prevalence of active digital ulcers (DU) decreased (16% to 13%, p= 0.040), while a history of DU (24% to 30%, p< 0.001) increased. Year-by-year and nonlinear increases were noted for ERA and CCB whereas nonlinear increase was observed for PDE5i. Year-by-year and nonlinear decrease was observed for Iloprost prescription.

Conclusion: A significant change has occurred over time in vascular medication use in SSc patients, with increased utilisation of ERA, PDE5i, CCB, and anti-platelet therapies, suggesting the adoption of more proactive and/or preventive treatment strategies.

Keywords: Medication; Prescription; Scleroderma; Systemic sclerosis; Temporal; Vascular.

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