Progressive skin fibrosis is associated with a decline in lung function and worse survival in patients with diffuse cutaneous systemic sclerosis in the european scleroderma trials and research (eustar) cohort /

Wanlong Wu; Suzana Jordan; Nicole Graf; Janethe de Oliveira Pena; John Curram; Yannick Allanore; Marco Matucci-Cerinic; Janet E Pope; Christopher P Denton; Dinesh Khanna; Oliver Distler; Serena Guiducci; Ulrich Walker; Veronika Jaeger; Bettina Bannert; Giovanni Lapadula; Radim Becvarare; Maurizio Cutolo; Gabriele Valentini; Elise Siegert; Simona Rednic; C Montecucco; Patricia E Carreira; Srdan Novak; László Czirják; Cecilia Varju; Carlo Chizzolini; Daniela Allai; Eugene J Kucharz; Franco Cozzi; Blaz Rozman; Carmel Mallia; Armando Gabrielli; Dominique Farge Bancel; Paolo Airò; Roger Hesselstrand; Duska Martinovic; Alexandra Balbir-Gurman; Yolanda Braun-Moscovici; Nicolas Hunzelmann; Raffaele Pellerito; Paola Caramaschi; Carol Black; Nemanja Damjanov; Jörg Henes; Vera Ortiz Santamaria; Stefan Heitmann; Matthias Seidel; José Antonio Pereira Da Silva; Bojana Stamenkovic; Carlo Francesco Selmi; Mohammed Tikly; Lev N Denisov; Ulf Müller-Ladner; Merete Engelhart; Eric Hachulla; Valeria Riccieri; Ruxandra Maria Ionescu; Carina Mihai; Cord Sunderkötter; Annegret Kuhn; Georg Schett; Jörg Distler; Pierluigi Meroni; Francesca Ingegnoli; Luc Mouthon; Filip De Keyser; Vanessa Smith; Francesco Paolo Cantatore; Ada Corrado; Susanne Ullman; Line Iversen; Maria Rosa Pozzi; Kilian Eyerich; Rüdiger Hein; Elisabeth Knott; Piotr Wiland; Magdalena Szmyrka-Kaczmarek; Renata Sokolik; Ewa Morgiel; Marta Madej; Juan Jose Alegre-Sancho; Brigitte Krummel-Lorenz; Petra Saar; Martin Aringer; Claudia Günther; Erler Anne; Rene Westhovens; Ellen De Langhe; Jan Lenaerts; Branimir Anic; Marko Baresic; Miroslav Mayer; Maria Üprus; Kati Otsa; Sule Yavuz; Sebastião Cezar Radominski; Carolina de Souza Müller; Valderílio Feijó Azevedo; Sergei Popa; Thierry Zenone; Simon Stebbings; John Highton; Alessandro Mathieu; Alessandra Vacca; Lisa Stamp; Peter Chapman; John O’donnell; Kamal Solanki; Alan Doube; Douglas Veale; Marie O’rourke; Esthela Loyo; Mengtao Li; Edoardo Rosato; Antonio Amoroso; Antonietta Gigante; Fahrettin Oksel; Figen Yargucu; Cristina-Mihaela Tanaseanu; Monica Popescu; Alina Dumitrascu; Isabela Tiglea; Rosario Foti; Elisa Visalli; Alessia Benenati; Giorgio Amato; Codrina Ancuta; Rodica Chirieac; Peter Villiger; Sabine Adler; Diana Dan; Paloma García de la Peña Lefebvre; Silvia Rodriguez Rubio; Marta Valero Exposito; Jean Sibilia; Emmanuel Chatelus; Jacques Eric Gottenberg; Hélène Chifflot; Ira Litinsky; Francesco Del Galdo; Algirdas Venalis; Lesley Ann Saketkoo; Joseph A Lasky; Eduardo Kerzberg; Fabiana Montoya; Vanesa Cosentino; Massimiliano Limonta; Antonio Luca Brucato; Elide Lupi; François Spertini; Camillo Ribi; Guillaume Buss; Thierry Martin; Aurélien Guffroy; Vincent Poindron; Lori Chung; Tim Schmeiser; Pawel Zebryk; Nuno Riso; Gabriela Riemekasten; Elena Rezus; Piercarlo Sarzi Puttini

doi:10.1136/annrheumdis-2018-213455

Title	Progressive skin fibrosis is associated with a decline in lung function and worse survival in patients with diffuse cutaneous systemic sclerosis in the european scleroderma trials and research (eustar) cohort /
Authors	Wu, Wanlong ; Jordan, Suzana ; Graf, Nicole ; de Oliveira Pena, Janethe ; Curram, John ; Allanore, Yannick ; Matucci-Cerinic, Marco ; Pope, Janet E ; Denton, Christopher P ; Khanna, Dinesh ; Distler, Oliver ; Guiducci, Serena ; Walker, Ulrich ; Jaeger, Veronika ; Bannert, Bettina ; Lapadula, Giovanni ; Becvarare, Radim ; Cutolo, Maurizio ; Valentini, Gabriele ; Siegert, Elise ; Rednic, Simona ; Montecucco, C ; Carreira, Patricia E ; Novak, Srdan ; Czirják, László ; Varju, Cecilia ; Chizzolini, Carlo ; Allai, Daniela ; Kucharz, Eugene J ; Cozzi, Franco ; Rozman, Blaz ; Mallia, Carmel ; Gabrielli, Armando ; Bancel, Dominique Farge ; Airò, Paolo ; Hesselstrand, Roger ; Martinovic, Duska ; Balbir-Gurman, Alexandra ; Braun-Moscovici, Yolanda ; Hunzelmann, Nicolas ; Pellerito, Raffaele ; Caramaschi, Paola ; Black, Carol ; Damjanov, Nemanja ; Henes, Jörg ; Santamaria, Vera Ortiz ; Heitmann, Stefan ; Seidel, Matthias ; Pereira Da Silva, José Antonio ; Stamenkovic, Bojana ; Selmi, Carlo Francesco ; Tikly, Mohammed ; Denisov, Lev N ; Müller-Ladner, Ulf ; Engelhart, Merete ; Hachulla, Eric ; Riccieri, Valeria ; Ionescu, Ruxandra Maria ; Mihai, Carina ; Sunderkötter, Cord ; Kuhn, Annegret ; Schett, Georg ; Distler, Jörg ; Meroni, Pierluigi ; Ingegnoli, Francesca ; Mouthon, Luc ; De Keyser, Filip ; Smith, Vanessa ; Cantatore, Francesco Paolo ; Corrado, Ada ; Ullman, Susanne ; Iversen, Line ; Pozzi, Maria Rosa ; Eyerich, Kilian ; Hein, Rüdiger ; Knott, Elisabeth ; Wiland, Piotr ; Szmyrka-Kaczmarek, Magdalena ; Sokolik, Renata ; Morgiel, Ewa ; Madej, Marta ; Alegre-Sancho, Juan Jose ; Krummel-Lorenz, Brigitte ; Saar, Petra ; Aringer, Martin ; Günther, Claudia ; Anne, Erler ; Westhovens, Rene ; De Langhe, Ellen ; Lenaerts, Jan ; Anic, Branimir ; Baresic, Marko ; Mayer, Miroslav ; Üprus, Maria ; Otsa, Kati ; Yavuz, Sule ; Radominski, Sebastião Cezar ; de Souza Müller, Carolina ; Azevedo, Valderílio Feijó ; Popa, Sergei ; Zenone, Thierry ; Stebbings, Simon ; Highton, John ; Mathieu, Alessandro ; Vacca, Alessandra ; Stamp, Lisa ; Chapman, Peter ; O’donnell, John ; Solanki, Kamal ; Doube, Alan ; Veale, Douglas ; O’rourke, Marie ; Loyo, Esthela ; Li, Mengtao ; Rosato, Edoardo ; Amoroso, Antonio ; Gigante, Antonietta ; Oksel, Fahrettin ; Yargucu, Figen ; Tanaseanu, Cristina-Mihaela ; Popescu, Monica ; Dumitrascu, Alina ; Tiglea, Isabela ; Foti, Rosario ; Visalli, Elisa ; Benenati, Alessia ; Amato, Giorgio ; Ancuta, Codrina ; Chirieac, Rodica ; Villiger, Peter ; Adler, Sabine ; Dan, Diana ; de la Peña Lefebvre, Paloma García ; Rubio, Silvia Rodriguez ; Exposito, Marta Valero ; Sibilia, Jean ; Chatelus, Emmanuel ; Gottenberg, Jacques Eric ; Chifflot, Hélène ; Litinsky, Ira ; Del Galdo, Francesco ; Venalis, Algirdas ; Saketkoo, Lesley Ann ; Lasky, Joseph A ; Kerzberg, Eduardo ; Montoya, Fabiana ; Cosentino, Vanesa ; Limonta, Massimiliano ; Brucato, Antonio Luca ; Lupi, Elide ; Spertini, François ; Ribi, Camillo ; Buss, Guillaume ; Martin, Thierry ; Guffroy, Aurélien ; Poindron, Vincent ; Chung, Lori ; Schmeiser, Tim ; Zebryk, Pawel ; Riso, Nuno ; Riemekasten, Gabriela ; Rezus, Elena ; Sarzi Puttini, Piercarlo
DOI	10.1136/annrheumdis-2018-213455
Full Text
Is Part of	Annals of the Rheumatic Diseases.. BMJ Publishing Group. 2019, 78, 5, 648-656.. ISSN 0003-4967. eISSN 1468-2060
Keywords [eng]	All-cause death ; Diffuse cutaneous systemic sclerosis ; Lung function decline ; Progressive skin fibrosis ; Visceral organ progression
Abstract [eng]	Objectives To determine whether progressive skin fibrosis is associated with visceral organ progression and mortality during follow-up in patients with diffuse cutaneous systemic sclerosis (dcSSc). Methods We evaluated patients from the European Scleroderma Trials and Research database with dcSSc, baseline modified Rodnan skin score (mRSS) ≥7, valid mRSS at 12±3 months after baseline and ≥1 annual follow-up visit. Progressive skin fibrosis was defined as an increase in mRSS >5 and ≥25% from baseline to 12±3 months. Outcomes were pulmonary, cardiovascular and renal progression, and all-cause death. Associations between skin progression and outcomes were evaluated by Kaplan-Meier survival analysis and multivariable Cox regression. Results Of 1021 included patients, 78 (7.6%) had progressive skin fibrosis (skin progressors). Median follow-up was 3.4 years. Survival analyses indicated that skin progressors had a significantly higher probability of FVC decline ≥10% (53.6% vs 34.4%; p<0.001) and all-cause death (15.4% vs 7.3%; p=0.003) than non-progressors. These significant associations were also found in subgroup analyses of patients with either low baseline mRSS (≤22/51) or short disease duration (≤15 months). In multivariable analyses, skin progression within 1 year was independently associated with FVC decline ≥10% (HR 1.79, 95% CI 1.20 to 2.65) and all-cause death (HR 2.58, 95% CI 1.31 to 5.09). Conclusions Progressive skin fibrosis within 1 year is associated with decline in lung function and worse survival in dcSSc during follow-up. These results confirm mRSS as a surrogate marker in dcSSc, which will be helpful for cohort enrichment in future trials and risk stratification in clinical practice.
Published	BMJ Publishing Group
Type	Journal article
Language	English
Publication date	2019
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„Progressive skin fibrosis is associated with a decline in lung function and worse survival in patients with diffuse cutaneous systemic sclerosis in the european scleroderma trials and research (eustar) cohort /“