Treatment outcome in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study (ESOS)

Herrick AL, Pan X, Peytrignet S, Lunt M, Hesselstrand R, Mouthon L, Silman A, Brown E, Czirjak L, Distler J, Distler O, Fligelstone K, Gregory WJ, Ochiel R, Vonk M, Ancuta C, Ong VH, Farge D, Hudson M, Matucci-Cerinic M, Balbir-Gurman A, Midtvedt O, Jordan AC, Jobanputra P, Stevens W, Moinzadeh P, Hall FC, Agard C, Anderson ME, Diot E, Madhok R, Akil M, Buch MH, Chung L, Damjanov N, Gunawardena H, Lanyon P, Ahmad Y, Chakravarty K, Jacobsen S, Macgregor AJ, Mchugh N, Mueller-Ladner U, Riemekasten G, Becker M, Roddy J, Carreira PE, Fauchais AL, Hachulla E, Hamilton J, Inanc M, Mclaren JS, Van Laar JM, Pathare S, Proudman S, Rudin A, Sahhar J, Coppere B, Serratrice C, Sheeran T, Veale DJ, Grange C, Trad GS, Denton CP (2017)


Publication Type: Journal article

Publication year: 2017

Journal

DOI: 10.1136/annrheumdis-2016-210503

Abstract

The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches.This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival.Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: -4.0 (-5.2 to -2.7) units for methotrexate, -4.1 (-5.3 to -2.9) for MMF, -3.3 (-4.9 to -1.7) for cyclophosphamide and -2.2 (-4.0 to -0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months.These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed.NCT02339441.

Authors with CRIS profile

Involved external institutions

James Cook University Hospital GB United Kingdom (GB) University of Adelaide AU Australia (AU) University of Gothenburg / Göteborgs universitet SE Sweden (SE) Monash University AU Australia (AU) Hôpital Edouard Herriot FR France (FR) Hôpital Saint Joseph FR France (FR) Cannock Chase Hospital GB United Kingdom (GB) St Vincent's University Hospital IE Ireland (IE) Hospices Civils de Lyon (CHU) FR France (FR) Assistance Publique-Hôpitaux de Paris (AP-HP) FR France (FR) UCL Centre for Rheumatology and Connective Tissue Diseases GB United Kingdom (GB) Hospital Universitario 12 de Octubre ES Spain (ES) University of Manchester GB United Kingdom (GB) Lund University / Lunds universitet SE Sweden (SE) University of Paris 5 - René Descartes / Université Paris V René Descartes FR France (FR) University of Oxford GB United Kingdom (GB) University of Pécs / Pécsi Tudományegyetem HU Hungary (HU) University of Zurich / Universität Zürich (UZH) CH Switzerland (CH) University College London (UCL) GB United Kingdom (GB) Salford Royal NHS Foundation Trust GB United Kingdom (GB) Radboud University Nijmegen NL Netherlands (NL) Grigore T. Popa University of Medicine and Pharmacy / Universitatea de Medicină și Farmacie "Grigore T. Popa" (UMF Iași) RO Romania (RO) University of Paris 7 - Denis Diderot / Université Paris VII Denis Diderot FR France (FR) Hôpital général juif - Jewish General Hospital CA Canada (CA) Università degli Studi di Firenze / University of Florence IT Italy (IT) Rappaport Faculty of Medicine IL Israel (IL) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet NO Norway (NO) University Hospitals Birmingham NHS Foundation Trust GB United Kingdom (GB) St Vincent's Hospital AU Australia (AU) Universität zu Köln DE Germany (DE) Cambridge University Hospital GB United Kingdom (GB) Université de Nantes FR France (FR) The University of Liverpool GB United Kingdom (GB) Centre Hospitalier Régional Universitaire de Tours FR France (FR) Glasgow Royal Infirmary (GRI) GB United Kingdom (GB) Sheffield Teaching Hospitals NHS Foundation Trust GB United Kingdom (GB) University of Leeds GB United Kingdom (GB) Stanford University US United States (USA) (US) North Bristol NHS Trust GB United Kingdom (GB) Nottingham University Hospitals GB United Kingdom (GB) Peter Maddison Rheumatology Centre GB United Kingdom (GB) Queen's Hospital GB United Kingdom (GB) University of Copenhagen DK Denmark (DK) University of East Anglia GB United Kingdom (GB) Royal National Hospital for Rheumatic Diseases GB United Kingdom (GB) University Medical Centre Utrecht (UMC Utrecht) NL Netherlands (NL) Universität zu Lübeck DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE) Royal Perth Hospital AU Australia (AU) Hospital Center University De Limoges Dupuytren FR France (FR) LILLE 1 University - Science and Technology FR France (FR) Gateshead Health NHS Foundation Trust GB United Kingdom (GB) Istanbul University / İstanbul Üniversitesi TR Turkey (TR) Whytemans Brae Hospital GB United Kingdom (GB) Justus-Liebig-Universität Gießen DE Germany (DE) University of Belgrade / Универзитет у Београду RS Serbia (RS)

How to cite

APA:

Herrick, A.L., Pan, X., Peytrignet, S., Lunt, M., Hesselstrand, R., Mouthon, L.,... Denton, C.P. (2017). Treatment outcome in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study (ESOS). Annals of the Rheumatic Diseases. https://dx.doi.org/10.1136/annrheumdis-2016-210503

MLA:

Herrick, Ariane L., et al. "Treatment outcome in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study (ESOS)." Annals of the Rheumatic Diseases (2017).

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