TY - JOUR
T1 - Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study
AU - Herrick, Ariane L.
AU - Peytrignet, Sebastien
AU - Lunt, Mark
AU - Pan, Xiaoyan
AU - Hesselstrand, Roger
AU - Mouthon, Luc
AU - Silman, Alan J.
AU - DInsdale, Graham
AU - Brown, Edith
AU - Czirják, László
AU - DIstler, Jörg H.W.
AU - DIstler, Oliver
AU - Fligelstone, Kim
AU - Gregory, William J.
AU - Ochiel, Rachel
AU - Vonk, Madelon C.
AU - Ancu, Codrina
AU - Ong, Voon H.
AU - Farge, Dominique
AU - Hudson, Marie
AU - Matucci-Cerinic, Marco
AU - Balbir-Gurman, Alexandra
AU - Midtvedt, Øyvind
AU - Jobanputra, Paresh
AU - Jordan, Alison C.
AU - Stevens, Wendy
AU - Moinzadeh, Pia
AU - Hall, Frances C.
AU - Agard, Christian
AU - Anderson, Marina E.
AU - DIot, Elisabeth
AU - Madhok, Rajan
AU - Akil, Mohammed
AU - Buch, Maya H.
AU - Chung, Lorinda
AU - Damjanov, Nemanja S.
AU - Gunawardena, Harsha
AU - Lanyon, Peter
AU - Ahmad, Yasmeen
AU - Chakravarty, Kuntal
AU - Jacobsen, Søren
AU - MacGregor, Alexander J.
AU - McHugh, Neil
AU - Müller-Ladner, Ulf
AU - Riemekasten, Gabriela
AU - Becker, Michael
AU - Roddy, Janet
AU - Carreira, Patricia E.
AU - Fauchais, Anne Laure
AU - Hachulla, Eric
AU - Hamilton, Jennifer
AU - Inanç, Murat
AU - McLaren, John S.
AU - Van Laar, Jacob M.
AU - Pathare, Sanjay
AU - Proudman, Susanna M.
AU - Rudin, Anna
AU - Sahhar, Joanne
AU - Coppere, Brigitte
AU - Serratrice, Christine
AU - Sheeran, Tom
AU - Veale, Douglas J.
AU - Grange, Claire
AU - Trad, Georges Selim
AU - Denton, Christopher P.
N1 - Funding Information:
1Centre for Musculoskeletal research, Salford royal nHS Foundation trust, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK 2nIHr Manchester Musculoskeletal Biomedical research Centre, Central Manchester nHS Foundation trust, Manchester Academic Health Science Centre, Manchester, UK 3Centre for Musculoskeletal research, the University of Manchester, Manchester Academic Health Science Centre, Manchester, UK 4department of rheumatology, Lund University, Lund, Sweden 5Service de Medicine Interne, Hôpital Cochin, Centre de référence pour les Vascularites nécrosantes et la Sclérodermie Systémique, Université paris descartes, paris, France 6nuffield department of orthopaedics, rheumatology and Musculoskeletal Sciences, University of oxford, oxford, UK 7University of Manchester, Manchester, Greater Manchester, UK 8department of rheumatology and Immunology, Medical Center, University of pecs, pecs, Hungary 9department of Internal Medicine III, University of Erlangen-nuremberg, Erlangen, Germany 10department of rheumatology, University of Zurich, Zurich, Switzerland 11royal Free London nHS Foundation trust, London, UK 12rehabilitation Services, Salford royal nHS Foundation trust, Salford, UK 13department of the rheumatic diseases, radboud University nijmegen Medical Centre, nijmegen, the netherlands 14rheumatology 2 department, ’Grigore t. popa’ University of Medicine and pharmacy, Clinical rehabilitation Hospital, Iasi, romania 15UCL division of Medicine, Centre for rheumatology and Connective tissue diseases, London, UK 16Unite 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 17Jewish General Hospital, Lady davis Institute and McGill University, Montreal, Canada 18department of Experimental and Clinical Medicine, division of rheumatology AoUC, University of Florence, Florence, Italy 19Shine rheumatology Unit, rambam Health Care Campus, rappaport Faculty of Medicine, Haifa, Israel 20rheumatology Unit, oslo University Hospital rikshospitalet, oslo, norway 21Queen Elizabeth Hospital Birmingham, UHB Foundation trust, Birmingham, UK 22St Vincent’s Hospital, Melbourne, Victoria, Australia 23department for dermatology, University of Cologne Kerpener Str, Cologne, Germany 24Cambridge University nHS Hospital Foundation trust, Cambridge, UK 25department of Internal Medicine, Hôtel-dieu Hospital, University of nantes, nantes, France 26University of Liverpool, Aintree University Hospital, Liverpool, UK 27Service de Médecine Interne, Hôpital Bretonneau tours, tours, France 28Centre for rheumatic diseases, royal Infirmary, Glasgow, UK 29Sheffield teaching Hospitals, Sheffield, UK 30Leeds Institute of rheumatic and Musculoskeletal Medicine, University of Leeds and nIHr Leeds Musculoskeletal Biomedical research Centre, Leeds teaching Hospitals nHS trust, Leeds, UK 31Stanford University, Stanford, California, USA 32University of Belgrade School of Medicine, Institute of rheumatology, Belgrade, Serbia 33Clinical and Academic rheumatology, north Bristol nHS trust, Bristol, UK 34nottingham University Hospitals nHS trust and nottingham nHS treatment Centre, nottingham, UK 35peter Maddison rheumatology Centre, Llandudno, UK 36Queens Hospital, romford, UK 37University of Copenhagen, Copenhagen Lupus and Vasculitis Clinic, Center for rheumatology and Spine diseases, rigshospitalet, Copenhagen, denmark 38norwich Medical School, University of East Anglia, norwich, UK 39royal national Hospital for rheumatic diseases, Bath, UK 40department of rheumatology and Clinical Immunology, Justus-Liebig University Giessen, Bad nauheim, Germany 41department of rheumatology, University of Lübeck, Lübeck, Germany 42department of rheumatology and Clinical Immunology, University Hospital Charité Berlin, Berlin, Germany 43department of rheumatology, royal perth Hospital, perth, Australia 44Servicio de reumatologia, Hospital Universitario 12 de octubre, Madrid, Spain 45Internal Medicine Unit, Limoges University Hospital, Limoges, France 46Centre national de référence Maladies Systémiques et Auto-immunes rares, département de Médecine Interne et Immunologie Clinique, Université de Lille, Lille, France 47Gateshead Hospitals Foundation trust, Gateshead, UK 48department of Internal Medicine, division of rheumatology, Istanbul University, Istanbul Medical Faculty, Istanbul, turkey 49Fife rheumatic diseases Unit, Whyteman’s Brae Hospital, Kirkcaldy, UK 50department of rheumatology and Clinical Immunology, UMC Utrecht, Utrecht, the netherlands 51James Cook University Hospital, Middlesbrough, UK 52rheumatology Unit, royal Adelaide Hospital, and discipline of Medicine, University of Adelaide, Adelaide, Victoria, Australia
Funding Information:
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.
Publisher Copyright:
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2018/4
Y1 - 2018/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85044451196&partnerID=8YFLogxK
U2 - 10.1136/annrheumdis-2017-211912
DO - 10.1136/annrheumdis-2017-211912
M3 - Journal articles
C2 - 29306872
AN - SCOPUS:85044451196
SN - 0003-4967
VL - 77
SP - 563
EP - 570
JO - Annals of the Rheumatic Diseases
JF - Annals of the Rheumatic Diseases
IS - 4
ER -
