Advertisement

Clinical Rheumatology

, Volume 39, Issue 1, pp 27–36 | Cite as

Use of vasoactive/vasodilating drugs for systemic sclerosis (SSc)-related digital ulcers (DUs) in expert tertiary centres: results from the analysis of the observational real-life DeSScipher study

  • Jelena BlagojevicEmail author
  • G. Abignano
  • J. Avouac
  • L. Cometi
  • M. Frerix
  • S. Bellando-Randone
  • S. Guiducci
  • C. Bruni
  • D. Huscher
  • V. K. Jaeger
  • V. Lóránd
  • B. Maurer
  • S. Nihtyanova
  • G. Riemekasten
  • E. Siegert
  • I. H. Tarner
  • S. Vettori
  • U. A. Walker
  • L. Czirják
  • C. P. Denton
  • O. Distler
  • Y. Allanore
  • U. Müller-Ladner
  • A. Moggi-Pignone
  • M. Matucci-Cerinic
  • F. Del Galdo
  • EUSTAR co-workers
Original Article
  • 307 Downloads
Part of the following topical collections:
  1. Updates in Systemic Sclerosis

Abstract

Introduction

DeSScipher is the first European multicentre study on management of systemic sclerosis (SSc), and its observational trial 1 (OT1) evaluated the efficacy of different drugs for digital ulcer (DU) prevention and healing. The aim of this study was to assess current use of vasoactive/vasodilating agents for SSc-related DU in the expert centres by analysing the baseline data of the DeSScipher OT1.

Method

Baseline characteristics of patients enrolled in the OT1 and data regarding DU were analysed.

Results

The most commonly used drugs, in both patients with and without DU, were calcium channel blockers (CCBs) (71.6%), followed by intravenous iloprost (20.8%), endothelin receptor antagonists (ERAs) (20.4%) and phosphodiesterase 5 (PDE-5) inhibitors (16.5%). Of patients, 32.6% with DU and 12.8% without DU received two drugs (p < 0.001), while 11.5% with DU and 1.9% without DU were treated with a combination of three or more agents (p < 0.001). Sixty-five percent of the patients with recurrent DU were treated with bosentan and/or sildenafil. However, 64 out of 277 patients with current DU (23.1%) and 101 (23.6%) patients with recurrent DU were on CCBs alone.

Conclusions

Our study shows that CCBs are still the most commonly used agents for DU management in SSc. The proportion of patients on combination therapy was low, even in patients with recurrent DU: almost one out of four patients with current and recurrent DU was on CCBs alone. Prospective analysis is planned to investigate the efficacy of different drugs/drug combinations on DU healing and prevention.

Key Points

The analysis of DeSScipher, the first European multicentre study on management of SSc, has shown that the most commonly used vasoactive/vasodilating drugs for DU were CCBs, followed by intravenous Iloprost, ERAs and PDE-5 inhibitors.

More than half of the patients with recurrent DU received bosentan and/or sildenafil.

However, the proportion of patients on combination therapy of more than one vasoactive/vasodilating drug was low and almost one out of four patients with current and recurrent DU was on CCBs alone.

Keywords

Digital ulcer Management Systemic sclerosis 

Notes

Funding information

This study, as part of the DeSScipher project, was supported by the European Community’s Framework Programme 7 (FP7-HEALTH-2012.2.4.4-2 Observational trials in rare diseases; grant agreement no. 305495). The authors report personal fees and non-financial support (to LV) from the European Union Seventh Framework Program 7 (FP7-HEALTH-2012.2.4.4-2 Observational trials in rare diseases]; grant agreement no. 305495).

Compliance with ethical standards

Disclosures

None.

Ethical approval

Ethical approval had been obtained from all participating centres’ local ethics committees, according to the declaration of Helsinki and its later amendments. Each patient signed a written informed consent form.

Supplementary material

10067_2019_4564_MOESM1_ESM.docx (25 kb)
ESM 1 (DOCX 25 kb)

References

  1. 1.
    Varga J, Trojanowska M, Kuwana M (2017) Pathogenesis of systemic sclerosis: recent insights of molecular and cellular mechanisms and therapeutic opportunities. J Scleroderma Relat Disord 2:137–152CrossRefGoogle Scholar
  2. 2.
    van Laar JM, Varga J (2015) The immunopathology of systemic sclerosis. Semin Immunopathol 37:439–441CrossRefGoogle Scholar
  3. 3.
    Matucci-Cerinic M, Krieg T, Guillevin L, Schwierin B, Rosenberg D, Cornelisse P, Denton CP (2016) Elucidating the burden of recurrent and chronic digital ulcers in systemic sclerosis: long-term results from the DUO Registry. Ann Rheum Dis 75:1770–1776CrossRefGoogle Scholar
  4. 4.
    Allanore Y, Denton CP, Krieg T, Cornelisse P, Rosenberg D, Schwierin B, DUO Investigators et al (2016) Clinical characteristics and predictors of gangrene in patients with systemic sclerosis and digital ulcers in the Digital Ulcer Outcome Registry: a prospective, observational cohort. Ann Rheum Dis 75:1736–1740CrossRefGoogle Scholar
  5. 5.
    Mihai C, Landewé R, van der Heijde D, Walker UA, Constantin PI, Gherghe AM, Ionescu R, Rednic S, Allanore Y, Avouac J, Czirják L, Hachulla E, Riemekasten G, Cozzi F, Airò P, Cutolo M, Mueller-Ladner U, Matucci-Cerinic M, EUSTAR co-authors (2016) Digital ulcers predict a worse disease course in patients with systemic sclerosis. Ann Rheum Dis 75:681–686CrossRefGoogle Scholar
  6. 6.
    Meunier P, Dequidt L, Barnetche T, Lazaro E, Duffau P, Richez C, Couzi L, Truchetet ME, Seneschal J, the FHU ACRONIM (2018) Increased risk of mortality in systemic sclerosis-associated digital ulcers: a systematic review and meta-analysis. J Eur Acad Dermatol Venereol 33:405–409.  https://doi.org/10.1111/jdv.15114 CrossRefPubMedGoogle Scholar
  7. 7.
    Kowal-Bielecka O, Fransen J, Avouac J, Becker M, Kulak A, Allanore Y, EUSTAR Coauthors et al (2017) Update of EULAR recommendations for the treatment of systemic sclerosis. Ann Rheum Dis 76:1327–1339CrossRefGoogle Scholar
  8. 8.
    Walker UA, Tyndall A, Czirják L, Denton C, Farge-Bancel D, Kowal-Bielecka O et al (2017) Clinical risk assessment of organ manifestations in systemic sclerosis: a report from the EULAR Scleroderma Trials And Research group database. Ann Rheum Dis 66:754–763CrossRefGoogle Scholar
  9. 9.
    Suliman YA, Bruni C, Johnson SR, Praino E, Alemam M, Borazan N, Cometi L, Myers B, Khanna D, Allanore Y, Baron M, Krieg T, Herrick A, Afonso A, Distler O, Kafaja S, Denton CP, Matucci-Cerinic M, Furst DE (2017) Defining skin ulcers in systemic sclerosis: systematic literature review and proposed World Scleroderma Foundation (WSF) definition. J Scleroderma Relat Disord 2:115–120CrossRefGoogle Scholar
  10. 10.
    Amanzi L, Braschi F, Fiori G, Galluccio F, Miniati I, Guiducci S, Conforti ML, Kaloudi O, Nacci F, Sacu O, Candelieri A, Pignone A, Rasero L, Conforti D, Matucci-Cerinic M (2010) Digital ulcers in scleroderma: staging, characteristics and sub-setting through observation of 1614 digital lesions. Rheumatology (Oxford) 49:1374–1382CrossRefGoogle Scholar
  11. 11.
    van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, Matucci-Cerinic M, Naden RP, Medsger TA Jr, Carreira PE, Riemekasten G, Clements PJ, Denton CP, Distler O, Allanore Y, Furst DE, Gabrielli A, Mayes MD, van Laar J, Seibold JR, Czirjak L, Steen VD, Inanc M, Kowal-Bielecka O, Müller-Ladner U, Valentini G, Veale DJ, Vonk MC, Walker UA, Chung L, Collier DH, Csuka ME, Fessler BJ, Guiducci S, Herrick A, Hsu VM, Jimenez S, Kahaleh B, Merkel PA, Sierakowski S, Silver RM, Simms RW, Varga J, Pope JE (2013) Classification criteria for systemic sclerosis: an ACR-EULAR Collaborative Initiative. Arthritis Rheum 65:2737–2747CrossRefGoogle Scholar
  12. 12.
    Denton CP, Krieg T, Guillevin L, Schwierin B, Rosenberg D, Silkey M, Zultak M, Matucci-Cerinic M, DUO Registry investigators (2012) Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry. Ann Rheum Dis 71:718–721CrossRefGoogle Scholar
  13. 13.
    Wirz EG, Jaeger VK, Allanore Y, Riemekasten G, Hachulla E, Distler O, Airò P, Carreira PE, Tikly M, Vettori S, Balbir Gurman A, Damjanov N, Müller-Ladner U, Distler J, Li M, Häusermann P, Walker UA, EUSTAR coauthors (2016) Incidence and predictors of cutaneous manifestations during the early course of systemic sclerosis: a 10-year longitudinal study from the EUSTAR database. Ann Rheum Dis 75:1285–1292CrossRefGoogle Scholar
  14. 14.
    Ferri C, Valentini G, Cozzi F, Sebastiani M, Michelassi C, La Montagna G et al (2002) Systemic sclerosis: demographic, clinical, and serologic features and survival in 1,012 Italian patients. Medicine 81:139–153CrossRefGoogle Scholar
  15. 15.
    Hachulla E, Clerson P, Launay D, Lambert M, Morell-Dubois S, Queyrel V et al (2007) Natural history of ischemic digital ulcers in systemic sclerosis: single-center retrospective longitudinal study. J Rheumatol 34:2423–2430PubMedGoogle Scholar
  16. 16.
    Tiev KP, Diot E, Clerson P, Dupuis-Simeon F, Hachulla E, Hatron PY et al (2009) Clinical features of scleroderma patients with or without prior or current ischemic digital ulcers: post-hoc analysis of a nationwide multicenter cohort (ItinerAIR-Sclerodermie). J Rheumatol 36:1470–1476CrossRefGoogle Scholar
  17. 17.
    Khimdas S, Harding S, Bonner A, Zummer B, Baron M, Pope J (2011) Associations with digital ulcers in a large cohort of systemic sclerosis: results from the Canadian Scleroderma Research Group registry. Arthritis Care Res 63:142–149CrossRefGoogle Scholar
  18. 18.
    Silva I, Teixeira A, Oliveira J, Almeida I, Almeida R, Águas A, Vasconcelos C (2015) Endothelial dysfunction and nailfold videocapillaroscopy pattern as predictors of digital ulcers in systemic sclerosis: a cohort study and review of the literature. Clin Rev Allergy Immunol 49:240–252CrossRefGoogle Scholar
  19. 19.
    Xu D, Li MT, Hou Y, Wang Q, Hu CJ, Song N, Zhao JL, Zeng XF, Zhang FC (2013) Clinical characteristics of systemic sclerosis patients with digital ulcers in China. Clin Exp Rheumatol 31(2 Suppl 76):46–49PubMedGoogle Scholar
  20. 20.
    Jaeger VK, Valentini G, Hachulla E, Cozzi F, Distler O, Airó P, Czirják L, Allanore Y, Siegert E, Rosato E, Matucci-Cerinic M, Caimmi C, Henes J, Carreira PE, Smith V, del Galdo F, Denton CP, Ullman S, de Langhe E, Riccieri V, Alegre-Sancho JJ, Rednic S, Müller-Ladner U, Walker UA, EUSTAR coauthors (2018) Smoking in systemic sclerosis: a longitudinal European Scleroderma Trials and Research Group Study. Arthritis Rheum 70:1829–1834.  https://doi.org/10.1002/art.40557 CrossRefGoogle Scholar
  21. 21.
    Moinzadeh P, Riemekasten G, Siegert E, Fierlbeck G, Henes J, Blank N, Melchers I, German Network for Systemic Scleroderma et al (2016) Vasoactive therapy in systemic sclerosis: real-life therapeutic practice in more than 3000 patients. J Rheumatol 43:66–74CrossRefGoogle Scholar
  22. 22.
    Pope J, Harding S, Khimdas S, Bonner A, Baron M, Canadian Scleroderma Research Group (2012) Agreement with guidelines from a large database for management of systemic sclerosis: results from the Canadian Scleroderma. J Rheumatol 39:524–531CrossRefGoogle Scholar
  23. 23.
    Ntelis K, Solomou EE, Sakkas L, Liossis SN, Daoussis D (2017) The role of platelets in autoimmunity, vasculopathy, and fibrosis: implications for systemic sclerosis. Semin Arthritis Rheum 47:409–441CrossRefGoogle Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2019

Authors and Affiliations

  • Jelena Blagojevic
    • 1
    Email author
  • G. Abignano
    • 2
    • 3
  • J. Avouac
    • 4
  • L. Cometi
    • 1
  • M. Frerix
    • 5
  • S. Bellando-Randone
    • 1
  • S. Guiducci
    • 1
  • C. Bruni
    • 1
  • D. Huscher
    • 6
  • V. K. Jaeger
    • 7
  • V. Lóránd
    • 8
  • B. Maurer
    • 9
  • S. Nihtyanova
    • 10
  • G. Riemekasten
    • 11
  • E. Siegert
    • 12
  • I. H. Tarner
    • 5
  • S. Vettori
    • 13
  • U. A. Walker
    • 7
  • L. Czirják
    • 8
  • C. P. Denton
    • 10
  • O. Distler
    • 9
  • Y. Allanore
    • 4
  • U. Müller-Ladner
    • 5
  • A. Moggi-Pignone
    • 14
  • M. Matucci-Cerinic
    • 1
  • F. Del Galdo
    • 3
  • EUSTAR co-workers
  1. 1.Department of Experimental and Clinical Medicine, Department of Geriatric Medicine, Division of Rheumatology and Scleroderma Unit AOUCUniversity of FlorenceFlorenceItaly
  2. 2.Rheumatology Institute of Lucania (IReL), Rheumatology Department of LucaniaSan Carlo Hospital of Potenza and Madonna delle Grazie Hospital of MateraPotenzaItaly
  3. 3.NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust and Leeds Institute of Rheumatic and Musculoskeletal MedicineUniversity of LeedsLeedsUK
  4. 4.Department of RheumatologyUniversity of Paris DescartesParisFrance
  5. 5.Department of Rheumatology and Clinical Immunology, Kerckhoff Klinik GmbHCampus of the Justus-Liebig University GiessenBad NauheimGermany
  6. 6.Institute of Biometry and Clinical EpidemiologyCharité – Universitätsmedizin Berlin, corporate member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, and Berlin Institute of HealthBerlinGermany
  7. 7.Department of RheumatologyUniversity of BaselBaselSwitzerland
  8. 8.Department of Rheumatology and ImmunologyUniversity of PécsPecsHungary
  9. 9.Department of RheumatologyUniversity Hospital ZurichZurichSwitzerland
  10. 10.Department of RheumatologyUniversity College London, Royal Free HospitalLondonUK
  11. 11.Clinic of Rheumatology and Clinical ImmunologyUniversity of LübeckLubeckGermany
  12. 12.Department of Rheumatology and Clinical ImmunologyCharité – Universitaetsmedizin Berlin, corporate member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, and Berlin Institute of HealthBerlinGermany
  13. 13.Rheumatology Section, Department of Precision MedicineUniversity of Campania “Luigi Vanvitelli”NaplesItaly
  14. 14.Department of Experimental and Clinical Medicine, Department of Emergency, Division of Medicine IV AOUCUniversity of FlorenceFlorenceItaly

Personalised recommendations