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Ann Rheum Dis. 2018 Apr;77(4):563-570. doi: 10.1136/annrheumdis-2017-211912. Epub 2018 Jan 6.

Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study.

Author information

1
Centre for Musculoskeletal Research, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
2
NIHR Manchester Musculoskeletal Biomedical Research Centre, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
3
Centre for Musculoskeletal Research, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
4
Department of Rheumatology, Lund University, Lund, Sweden.
5
Service de Medicine Interne, Hôpital Cochin, Centre de Référence pour les Vascularites Nécrosantes et la Sclérodermie Systémique, Université Paris Descartes, Paris, France.
6
Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
7
University of Manchester, Manchester, Greater Manchester, UK.
8
Department of Rheumatology and Immunology, Medical Center, University of Pecs, Pecs, Hungary.
9
Department of Internal Medicine III, University of Erlangen-Nuremberg, Erlangen, Germany.
10
Department of Rheumatology, University of Zurich, Zurich, Switzerland.
11
Royal Free London NHS Foundation Trust, London, UK.
12
Rehabilitation Services, Salford Royal NHS Foundation Trust, Salford, UK.
13
Department of the Rheumatic Diseases, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
14
Rheumatology 2 Department, 'Grigore T. Popa' University of Medicine and Pharmacy, Clinical Rehabilitation Hospital, Iasi, Romania.
15
UCL Division of Medicine, Centre for Rheumatology and Connective Tissue Diseases, London, UK.
16
Unite Clinique de Medicine Interne, Maladies Auto-immunes et Pathologie Vasculaire, UF 04, Hôpital Saint-Louis, AP-HP Assistance Publique des Hôpitaux de Paris, INSERM UMRS 1160, Paris Denis Diderot University, Paris, France.
17
Jewish General Hospital, Lady Davis Institute and McGill University, Montreal, Canada.
18
Department of Experimental and Clinical Medicine, Division of Rheumatology AOUC, University of Florence, Florence, Italy.
19
Shine Rheumatology Unit, Rambam Health Care Campus, Rappaport Faculty of Medicine, Haifa, Israel.
20
Rheumatology Unit, Oslo University Hospital Rikshospitalet, Oslo, Norway.
21
Queen Elizabeth Hospital Birmingham, UHB Foundation Trust, Birmingham, UK.
22
St Vincent's Hospital, Melbourne, Victoria, Australia.
23
Department for Dermatology, University of Cologne Kerpener Str, Cologne, Germany.
24
Cambridge University NHS Hospital Foundation Trust, Cambridge, UK.
25
Department of Internal Medicine, Hôtel-Dieu Hospital, University of Nantes, Nantes, France.
26
University of Liverpool, Aintree University Hospital, Liverpool, UK.
27
Service de Médecine Interne, Hôpital Bretonneau Tours, Tours, France.
28
Centre for Rheumatic Diseases, Royal Infirmary, Glasgow, UK.
29
Sheffield Teaching Hospitals, Sheffield, UK.
30
Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and NIHR Leeds Musculoskeletal Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
31
Stanford University, Stanford, California, USA.
32
University of Belgrade School of Medicine, Institute of Rheumatology, Belgrade, Serbia.
33
Clinical and Academic Rheumatology, North Bristol NHS Trust, Bristol, UK.
34
Nottingham University Hospitals NHS Trust and Nottingham NHS Treatment Centre, Nottingham, UK.
35
Peter Maddison Rheumatology Centre, Llandudno, UK.
36
Queens Hospital, Romford, UK.
37
University of Copenhagen, Copenhagen Lupus and Vasculitis Clinic, Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen, Denmark.
38
Norwich Medical School, University of East Anglia, Norwich, UK.
39
Royal National Hospital for Rheumatic Diseases, Bath, UK.
40
Department of Rheumatology and Clinical Immunology, Justus-Liebig University Giessen, Bad Nauheim, Germany.
41
Department of Rheumatology, University of Lübeck, Lübeck, Germany.
42
Department of Rheumatology and Clinical Immunology, University Hospital Charité Berlin, Berlin, Germany.
43
Department of Rheumatology, Royal Perth Hospital, Perth, Australia.
44
Servicio de Reumatologia, Hospital Universitario 12 de Octubre, Madrid, Spain.
45
Internal Medicine Unit, Limoges University Hospital, Limoges, France.
46
Centre National de Référence Maladies Systémiques et Auto-immunes Rares, Département de Médecine Interne et Immunologie Clinique, Université de Lille, Lille, France.
47
Gateshead Hospitals Foundation Trust, Gateshead, UK.
48
Department of Internal Medicine, Division of Rheumatology, Istanbul University, Istanbul Medical Faculty, Istanbul, Turkey.
49
Fife Rheumatic Diseases Unit, Whyteman's Brae Hospital, Kirkcaldy, UK.
50
Department of Rheumatology and Clinical Immunology, UMC Utrecht, Utrecht, The Netherlands.
51
James Cook University Hospital, Middlesbrough, UK.
52
Rheumatology Unit, Royal Adelaide Hospital, and Discipline of Medicine, University of Adelaide, Adelaide, Victoria, Australia.
53
Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.
54
Monash Health and Department Medicine, Monash Centre for Inflammatory Diseases, Monash University, Melbourne, Victoria, Australia.
55
Department of Internal Medicine, Hôpital Edouard Herriot, Lyon, France.
56
Department of Internal Medicine, Foundation Hospital Saint Joseph, Marseille, France.
57
Cannock Chase Hospital, Cannock, UK.
58
St Vincent's University Hospital, Dublin, Ireland.
59
Department of Internal Medicine, Centre Hospitalier Lyon Sud, Lyon, France.
60
Internal Medicine, Ambroise Paré Hospital, Boulogne-Billancourt, France.

Abstract

OBJECTIVES:

Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs).

METHODS:

The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. 'Progressors' were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV).

RESULTS:

66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%.

CONCLUSIONS:

Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years.

TRIAL REGISTRATION NUMBER:

NCT02339441.

KEYWORDS:

autoantibodies; outcomes research; systemic sclerosis

PMID:
29306872
PMCID:
PMC5890636
DOI:
10.1136/annrheumdis-2017-211912
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Competing interests: ALH has done consultancy work for Actelion, served on a Data Safety Monitoring Board for Apricus, received research funding and speaker’s fees from Actelion, and speaker’s fees from GSK. JHWD has consultancy relationships and/or has received research funding from Actelion, BMS, Celgene, Bayer Pharma, Boehringer Ingelheim, JB Therapeutics, Sanofi-Aventis, Novartis, UCB, GSK, Array BioPharma, Active Biotech, Galapagos, Inventiva, Medac, Pfizer, Anamar and RuiYi, and is stock owner of 4D Science. OD has received consultancy fees from 4D Science, Actelion, Active Biotech, Bayer, Biogenidec, BMS, Boehringer Ingelheim, EpiPharm, Ergonex, espeRare Foundation, Genentech/Roche, GSK, Inventiva, Lilly, Medac, Medimmune, Pharmacyclics, Pfizer, Serodapharm, Sinoxa and UCB, and received research grants from Actelion, Bayer, Boehringer Ingelheim, Ergonex, Pfizer and Sanofi, and has a patent mir-29 for the treatment of systemic sclerosis licensed. WJG has received teaching fees from Pfizer. CA has served as a consultant for AbbVie, Pfizer, Roche, UCB, MSD, BMS and Novartis, and has received research funding and speaker fees from AbbVie, Pfizer, Roche, UCB, MSD, BMS and Novartis. FCH has received research funding from Actelion. MEA has undertaken advisory board work and received honoraria from Actelion, and received speaker’s fees from Bristol-Myers Squibb. NSD has done consultancy for AbbVie, Pfizer, Roche and MSD, and received speaker’s fees from AbbVie, Boehringer-Ingelheim, Pfizer, Richter Gedeon, Roche and MSD. HG has done consultancy work and received honoraria from Actelion. UM-L is funded in part by EUSTAR, EULAR and the European Community (Desscipher programme). JMvL has received honoraria from Eli Lilly, Pfizer, Roche, MSD and BMS. SP has received research grants from Actelion Pharmaceuticals Australia, Bayer, GlaxoSmithKline Australia and Pfizer, and speaker fees from Actelion. AR receives funding from AstraZeneca. CPD has done consultancy for GSK, Actelion, Bayer, Inventiva and Merck-Serono, received research grant funding from GSK, Actelion, CSL Behring and Inventiva, received speaker’s fees from Bayer and given trial advice to Merck-Serono.

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