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

Wu, W.; Jordan, S.; Graf, N.; de Oliveira Pena, J.; Curram, J.; Allanore, Y.; Matucci-Cerinic, M.; Pope, J.E.; Denton, C.P.; Khanna, D.; Distler, O.; Guiducci, S.; Walker, U.; Jaeger, V.; Bannert, B.; Lapadula, G.; Becvarare, R.; Cutolo, M.; Valentini, G.; Siegert, E.; Rednic, S.; Montecucco, C.; Carreira, P.E.; Novak, S.; Czirjak, L.; Varju, C.; Chizzolini, C.; Allai, D.; Kucharz, E.J.; Cozzi, F.; Rozman, B.; Mallia, C.; Gabrielli, A.; Bancel, D.F.; Airo, P.; Hesselstrand, R.; Martinovic, D.; Balbir-Gurman, A.; Braun-Moscovici, Y.; Hunzelmann, N.; Pellerito, R.; Caramaschi, P.; Black, C.; Damjanov, N.; Henes, J.; Santamaria, V.O.; Heitmann, S.; Seidel, M.; Pereira Da Silva, J.A.; Stamenkovic, B.; Selmi, C.F.; Tikly, M.; Denisov, L.N.; Muller-Ladner, U.; Engelhart, M.; Hachulla, E.; Riccieri, V.; Ionescu, R.M.; Mihai, C.; Sunderkotter, C.; Kuhn, A.; Schett, G.; Distler, J.; Meroni, P.; Ingegnoli, F.; Mouthon, L.; De Keyser, F.; Smith, V.; Cantatore, F.P.; Corrado, A.; Ullman, S.; Iversen, L.; Pozzi, M.R.; Eyerich, K.; Hein, R.; Knott, E.; Wiland, P.; Szmyrka-Kaczmarek, M.; Sokolik, R.; Morgiel, E.; Madej, M.; Alegre-Sancho, J.J.; Krummel-Lorenz, B.; Saar, P.; Aringer, M.; Gunther, C.; Anne, E.; Westhovens, R.; De Langhe, E.; Lenaerts, J.; Anic, B.; Baresic, M.; Mayer, M.; Uprus, M.; Otsa, K.; Yavuz, S.; Radominski, S.C.; de Souza Muller, C.; Azevedo, V.F.; Popa, S.; Zenone, T.; Stebbings, S.; Highton, J.; Mathieu, A.; Vacca, A.; Stamp, L.; Chapman, P.; O'Donnell, J.; Solanki, K.; Doube, A.; Veale, D.; O'Rourke, M.; Loyo, E.; Li, M.; Rosato, E.; Amoroso, A.; Gigante, A.; Oksel, F.; Yargucu, F.; Tanaseanu, C.-.; Popescu, M.; Dumitrascu, A.; Tiglea, I.; Foti, R.; Visalli, E.; Benenati, A.; Amato, G.; Ancuta, C.; Chirieac, R.; Villiger, P.; Adler, S.; Dan, D.; de la Pena Lefebvre, P.G.; Rubio, S.R.; Exposito, M.V.; Sibilia, J.; Chatelus, E.; Gottenberg, J.E.; Chifflot, H.; Litinsky, I.; Del Galdo, F.; Venalis, A.; Saketkoo, L.A.; Lasky, J.A.; Kerzberg, E.; Montoya, F.; Cosentino, V.; Limonta, M.; Brucato, A.L.; Lupi, E.; Spertini, F.; Ribi, C.; Buss, G.; Martin, T.; Guffroy, A.; Poindron, V.; Chung, L.; Schmeiser, T.; Zebryk, P.; Riso, N.; Riemekasten, G.; Rezus, E.; Sarzi Puttini, P.

doi:10.1136/annrheumdis-2018-213455

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.

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 / W. Wu, S. Jordan, N. Graf, J. de Oliveira Pena, J. Curram, Y. Allanore, M. Matucci-Cerinic, J.E. Pope, C.P. Denton, D. Khanna, O. Distler, S. Guiducci, U. Walker, V. Jaeger, B. Bannert, G. Lapadula, R. Becvarare, M. Cutolo, G. Valentini, E. Siegert, S. Rednic, C. Montecucco, P.E. Carreira, S. Novak, L. Czirjak, C. Varju, C. Chizzolini, D. Allai, E.J. Kucharz, F. Cozzi, B. Rozman, C. Mallia, A. Gabrielli, D.F. Bancel, P. Airo, R. Hesselstrand, D. Martinovic, A. Balbir-Gurman, Y. Braun-Moscovici, N. Hunzelmann, R. Pellerito, P. Caramaschi, C. Black, N. Damjanov, J. Henes, V.O. Santamaria, S. Heitmann, M. Seidel, J.A. Pereira Da Silva, B. Stamenkovic, C.F. Selmi, M. Tikly, L.N. Denisov, U. Muller-Ladner, M. Engelhart, E. Hachulla, V. Riccieri, R.M. Ionescu, C. Mihai, C. Sunderkotter, A. Kuhn, G. Schett, J. Distler, P. Meroni, F. Ingegnoli, L. Mouthon, F. De Keyser, V. Smith, F.P. Cantatore, A. Corrado, S. Ullman, L. Iversen, M.R. Pozzi, K. Eyerich, R. Hein, E. Knott, P. Wiland, M. Szmyrka-Kaczmarek, R. Sokolik, E. Morgiel, M. Madej, J.J. Alegre-Sancho, B. Krummel-Lorenz, P. Saar, M. Aringer, C. Gunther, E. Anne, R. Westhovens, E. De Langhe, J. Lenaerts, B. Anic, M. Baresic, M. Mayer, M. Uprus, K. Otsa, S. Yavuz, S.C. Radominski, C. de Souza Muller, V.F. Azevedo, S. Popa, T. Zenone, S. Stebbings, J. Highton, A. Mathieu, A. Vacca, L. Stamp, P. Chapman, J. O'Donnell, K. Solanki, A. Doube, D. Veale, M. O'Rourke, E. Loyo, M. Li, E. Rosato, A. Amoroso, A. Gigante, F. Oksel, F. Yargucu, C.-. Tanaseanu, M. Popescu, A. Dumitrascu, I. Tiglea, R. Foti, E. Visalli, A. Benenati, G. Amato, C. Ancuta, R. Chirieac, P. Villiger, S. Adler, D. Dan, P.G. de la Pena Lefebvre, S.R. Rubio, M.V. Exposito, J. Sibilia, E. Chatelus, J.E. Gottenberg, H. Chifflot, I. Litinsky, F. Del Galdo, A. Venalis, L.A. Saketkoo, J.A. Lasky, E. Kerzberg, F. Montoya, V. Cosentino, M. Limonta, A.L. Brucato, E. Lupi, F. Spertini, C. Ribi, G. Buss, T. Martin, A. Guffroy, V. Poindron, L. Chung, T. Schmeiser, P. Zebryk, N. Riso, G. Riemekasten, E. Rezus, P. Sarzi Puttini. - In: ANNALS OF THE RHEUMATIC DISEASES. - ISSN 0003-4967. - 78:5(2019), pp. 648-656. [10.1136/annrheumdis-2018-213455]

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

Wu W.;Jordan S.;Graf N.;de Oliveira Pena J.;Curram J.;Allanore Y.;Matucci-Cerinic M.;Pope J. E.;Denton C. P.;Khanna D.;Distler O.;Guiducci S.;Walker U.;Jaeger V.;Bannert B.;Lapadula G.;Becvarare R.;Cutolo M.;Valentini G.;Siegert E.;Rednic S.;Montecucco C.;Carreira P. E.;Novak S.;Czirjak L.;Varju C.;Chizzolini C.;Allai D.;Kucharz E. J.;Cozzi F.;Rozman B.;Mallia C.;Gabrielli A.;Bancel D. F.;Airo P.;Hesselstrand R.;Martinovic D.;Balbir-Gurman A.;Braun-Moscovici Y.;Hunzelmann N.;Pellerito R.;Caramaschi P.;Black C.;Damjanov N.;Henes J.;Santamaria V. O.;Heitmann S.;Seidel M.;Pereira Da Silva J. A.;Stamenkovic B.;Selmi C. F.;Tikly M.;Denisov L. N.;Muller-Ladner U.;Engelhart M.;Hachulla E.;Riccieri V.;Ionescu R. M.;Mihai C.;Sunderkotter C.;Kuhn A.;Schett G.;Distler J.;Meroni P.;F. Ingegnoli;Mouthon L.;De Keyser F.;Smith V.;Cantatore F. P.;Corrado A.;Ullman S.;Iversen L.;Pozzi M. R.;Eyerich K.;Hein R.;Knott E.;Wiland P.;Szmyrka-Kaczmarek M.;Sokolik R.;Morgiel E.;Madej M.;Alegre-Sancho J. J.;Krummel-Lorenz B.;Saar P.;Aringer M.;Gunther C.;Anne E.;Westhovens R.;De Langhe E.;Lenaerts J.;Anic B.;Baresic M.;Mayer M.;Uprus M.;Otsa K.;Yavuz S.;Radominski S. C.;de Souza Muller C.;Azevedo V. F.;Popa S.;Zenone T.;Stebbings S.;Highton J.;Mathieu A.;Vacca A.;Stamp L.;Chapman P.;O'donnell J.;Solanki K.;Doube A.;Veale D.;O'rourke M.;Loyo E.;Li M.;Rosato E.;Amoroso A.;Gigante A.;Oksel F.;Yargucu F.;Tanaseanu C. -M.;Popescu M.;Dumitrascu A.;Tiglea I.;Foti R.;Visalli E.;Benenati A.;Amato G.;Ancuta C.;Chirieac R.;Villiger P.;Adler S.;Dan D.;de la Pena Lefebvre P. G.;Rubio S. R.;Exposito M. V.;Sibilia J.;Chatelus E.;Gottenberg J. E.;Chifflot H.;Litinsky I.;Del Galdo F.;Venalis A.;Saketkoo L. A.;Lasky J. A.;Kerzberg E.;Montoya F.;Cosentino V.;Limonta M.;A.L. Brucato;Lupi E.;Spertini F.;Ribi C.;Buss G.;Martin T.;Guffroy A.;Poindron V.;Chung L.;Schmeiser T.;Zebryk P.;Riso N.;Riemekasten G.;Rezus E.;P. Sarzi Puttini^Ultimo

2019

Abstract

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.

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	Parole chiave
	
				All-cause death; Diffuse cutaneous systemic sclerosis; Lung function decline; Progressive skin fibrosis; Visceral organ progression
			
	Settori scientifico-disciplinari dell'articolo (sola visualizzazione)
	
				Settore MED/16 - Reumatologia
			
	Data di pubblicazione
	
				2019
			
	Rivista in ANCE
	
				ANNALS OF THE RHEUMATIC DISEASES
			
	DOI
	
				https://dx.doi.org/10.1136/annrheumdis-2018-213455
			
	Tipologia
	
				Article (author)
			
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				01 - Articolo su periodico

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