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