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Start Over Author "Yargucu, F." Topic systemic sclerosis
6 results on '"Yargucu, F."'

1. Late Skin Fibrosis in Systemic Sclerosis: A Study from the EUSTAR Cohort

Author

Michael Hughes 1 2, Suiyuan Huang 3 4, Juan Jose Alegre-Sancho 5, Patricia E Carreira 6, Merete Engelhart 7, Eric Hachulla 8, Joerg Henes 9, Eduardo Kerzberg 10, Maria Rosa Pozzi 11, Gabriela Riemekasten 12, Vanessa Smith 13, Gabriella Szücs 14, Marie Vanthuyne 15, Elisabetta Zanatta 16, Oliver Distler 17, Armando G Gabrielli 18, Anna-Maria Hoffmann-Vold 19, Virginia D Steen 20, Dinesh Khanna 3 21, EUSTAR Airò P, Allanore A, Ananieva Lp, Anic B, Balbir-Gurman A, Becvar R, Benvenuti F, Cantatore F P, Chung L S, Cuomo G, Cutolo M, Czirják L, Damjanov N, de Vries-Bouwstra J, Del Galdo F, Distler J, Eyerich K, Farge D, Foti R, Gheorghiu A M, Giollo A, Heitmann S, Herrick A, Hesselstrand R, Hsu I M, Hunzelmann N, Iannone F, Iudici M, Ionescuc M R, Ingegnoli F, Jose J, Joven B E, Kerzberg E, Kucharz E J, Kuwana M, Langhe E D, Launay D, Lefebvre P, Litinsky I, García de la Peña Lefebvre P, González-Martín J J, Li M, Loyo E, Martin T, Matucci-Cerinic M, Maurer B, Moroncini G, Mouthon L, Müller Cs, Müller-Ladner U, Novak S, Pastor P, Pecher A-C, Pellerito R, Pozzi M R, Oksel F, Rednic S, Rezus E, Riccieri V, Rosato E, Saketkoo L A, Salvador M J, Schmeiser T, Selmi C F, Sibilia J, Siegert E, Solanki K, Sommerlatte S, Spertini F, Stamenkovic B, Stamp L, Tanaseanu C-M, Tikly M, Tineo C, Ullman S, Üprus M, Vanthuyne M, Veale D, Walker U, Wiland P, Yargucu F, Yavuz S, University of Zurich, Michael Hughes, 1 2, Suiyuan Huang, 3 4, Juan Jose Alegre-Sancho, 5, Patricia, E Carreira 6, Merete Engelhart, 7, Eric Hachulla, 8, Joerg Henes, 9, Eduardo Kerzberg, 10, Maria Rosa Pozzi, 11, Gabriela Riemekasten, 12, Vanessa Smith, 13, Gabriella Szücs, 14, Marie Vanthuyne, 15, Elisabetta Zanatta, 16, Oliver Distler, 17, Armando, G Gabrielli 18, Anna-Maria Hoffmann-Vold, 19, Virginia, D Steen 20, Dinesh Khanna, 3 21, EUSTAR Airò, P, Allanore, A, Ananieva, Lp, Anic, B, Balbir-Gurman, A, Becvar, R, Benvenuti, F, Cantatore, F P, Chung, L S, Cuomo, G, Cutolo, M, Czirják, L, Damjanov, N, de Vries-Bouwstra, J, Del Galdo, F, Distler, J, Eyerich, K, Farge, D, Foti, R, Gheorghiu, A M, Giollo, A, Heitmann, S, Herrick, A, Hesselstrand, R, Hsu, I M, Hunzelmann, N, Iannone, F, Iudici, M, Ionescuc, M R, Ingegnoli, F, Jose, J, Joven, B E, Kerzberg, E, Kucharz, E J, Kuwana, M, Langhe, E D, Launay, D, Lefebvre, P, Litinsky, I, García de la Peña Lefebvre, P, González-Martín, J J, Li, M, Loyo, E, Martin, T, Matucci-Cerinic, M, Maurer, B, Moroncini, G, Mouthon, L, Müller, C, Müller-Ladner, U, Novak, S, Pastor, P, Pecher, A-C, Pellerito, R, Pozzi, M R, Oksel, F, Rednic, S, Rezus, E, Riccieri, V, Rosato, E, Saketkoo, L A, Salvador, M J, Schmeiser, T, Selmi, C F, Sibilia, J, Siegert, E, Solanki, K, Sommerlatte, S, Spertini, F, Stamenkovic, B, Stamp, L, Tanaseanu, C-M, Tikly, M, Tineo, C, Ullman, S, Üprus, M, Vanthuyne, M, Veale, D, Walker, U, Wiland, P, Yargucu, F, and Yavuz, S

Subjects
Rheumatology, Cohort enrichment, 10051 Rheumatology Clinic and Institute of Physical Medicine, Late disease, Systemic sclerosis, Pharmacology (medical), 610 Medicine & health, Fibrosis, Clinical trial design, Scleroderma, Skin
Abstract

Objectives The early trajectory of skin fibrosis provides insights into the disease course of systemic sclerosis (SSc) including mortality; however, little is known about late skin fibrosis. The aims of our study were to ascertain the prevalence and characteristics of late skin fibrosis in SSc. Methods We developed and tested three conceptual scenarios of late (>5 years after first non-RP feature) skin fibrosis including new worsening of skin disease, and failure to improve after worsening within 5-year window. We defined skin worsening as change in modified Rodnan skin score (mRSS) ≥5 units or ≥25%. Using strict inclusion criteria including complete mRSS, we identified 1,043 (out of 19 115) patients within the EUSTAR database for our analysis. We further restricted analysis within 887 (out of 1043) patients who had lcSSc or dcSSc at baseline. Results One-fifth of patients among the whole cohort (n = 208/1043, 19.9%) experienced mRSS worsening, including in patients with lcSSc or dcSSc at baseline (n = 193/887, 21.8%). This was largely due to new skin worsening after the 5-year window or failure to improve with worsening within the 5-year window. Patients with lower baseline mRSS and lcSSc were more likely to develop late skin fibrosis. Anti-Scl-70 was associated with progression from baseline lcSSc to dcSSc, and anticentromere was protective. Conclusions Late skin fibrosis is not uncommon in SSc. We have identified different patterns relevant to clinical practice and trial design. Late skin fibrosis is a neglected manifestation of SSc and warrants further investigation including to determine clinical outcomes and optimal therapeutic strategy.

Published
2022

2. Racial differences in systemic sclerosis disease presentation: A European Scleroderma Trials and Research group study

Author

Jaeger, Veronika K, Tikly, Mohammed, Dong, Xu, Siegert, Elise, Hachulla, Eric, Airò, Paolo, Valentini, Gabriele, Matucci Cerinic, Marco, Distler, Oliver, Cozzi, Franco, Carreira, Patricia, Allanore, Yannick, Müller-Ladner, Ulf, Ananieva, Lidia P, Balbir-Gurman, Alexandra, Distler, Jörg H W, Czirják, Laszlo, Mengtao, Li, Henes, Jörg, Jimenez, Sergio A, Smith, Vanessa, Damjanov, Nemanja, Denton, Christopher P, Delgaldo, Francesco, Saketkoo, Lesley Ann, Walker, Ulrich, A, Randone, Sb, Bannert, B, Iannone, F, Maurer, B, Jordan, S, Dobrota, R, Becker, M, Mihai, C, Becvarare, R, Tomčík, M, Bielecka, Ok, Gindzienska-Sieskiewicz, E, Karaszewska, K, Cutolo, M, Pizzorni, C, Paolino, S, Sulli, A, Ruaro, B, Alessandri, E, Riccardi, A, Giacco, V, Messitini, V, Irace, R, Kedor, C, Casteleyn, V, Hilger, J, Hoeppner, J, Rednic, S, Szabo, I, Petcu, A, Avouac, J, Camelia, F, Desbas, C, Vlachoyiannopoulos, P, Montecucco, C, Caporali, R, Cavagna, L, Stork, J, Inanc, M, Joven, Be, Novak, S, Anic, F, Varju, C, Minier, T, Chizzolini, C, Allai, D, Kucharz, Ej, Kotulska, A, Kopec-Medrek, M, Widuchowska, M, Dolnicar, As, Coleiro, B, Gabrielli, A, Manfredi, L, Benfaremo, D, Ferrarini, A, Bancel, Df, Hij, A, Lansiaux, P, Lazzaroni, Mg, Hesselstrand, R, Wuttge, D, Andréasson, R, Martinovic, D, Bozic, I, Radic, M, Braun-Moscovici, Y, Monaco, Al, Furini, F, Hunzelmann, N, Moinzadeh, P, Pellerito, R, Caimmi, C, Bertoldo, E, Morovic-Vergles, J, Culo, Im, Pecher, Ac, Santamaria, Vo, Heitmann, S, Codagnone, M, Pflugfelder, J, Krasowska, D, Michalska-Jakubus, M, Seidel, M, Hasler, P, Kretschmar, S, Kohm, M, Bajocchi, G, Salvador, Mj, Silva, Japd, Stamenkovic, B, Stankovic, A, Selmi, Cf, Santis, M, Ceribelli, A, Garzanova, L, Koneva, O, Starovoytova, M, Herrick, A, Puppo, F, Negrini, S, Murdaca, G, Engelhart, M, Szücs, G, Szamosi, S, de la Puente, C, Grande, Cs, Villanueva, Mjg, Midtvedt, Sø, Hoffmann-Vold, Am, Launay, D, Sobanski, V, Riccieri, V, Vasile, M, Ionescu, Rm, Opris, D, Sha, A, Woods, A, Gheorghiu, Am, Bojinca, M, Sunderkötter, C, Ehrchen, J, Ingegnoli, F, Mouthon, L, Dunogue, B, Chaigne, B, Legendre, P, Cantatore, Fp, Corrado, A, Ullman, S, Iversen, L, von Mühlen CA, Pozzi, Mr, Eyerich, K, Lauffer, F, Wiland, P, Szmyrka-Kaczmarek, M, Sokolik, R, Morgiel, E, Madej, M, Vanthuyne, M, Frédéric, H, Alegre-Sancho, Jj, Aringer, M, Herrmann, K, Günther, C, Westhovens, R, Langhe, E, Lenaerts, J, Anic, B, Baresic, M, Mayer, M, Üprus, M, Otsa, K, Yavuz, S, Granel, B, Radominski, Sc, De, C, Müller, S, Azevedo, Vf, Mendoza, F, Busquets, J, Popa, S, Agachi, S, Zenone, T, Pileckyte, M, Stebbings, S, Mathieu, A, Vacca, A, Sampaio-Barros, Pd, Stamp, L, Solanki, K, Silva, C, Schollum, J, Barns-Graham, H, Veale, D, O'Rourke, M, Loyo, E, Tineo, C, Paulino, G, Mohamed, Waaa, Rosato, E, Gigante, A, Oksel, F, Yargucu, F, Tanaseanu, Cm, Popescu, M, Dumitrascu, A, Tiglea, I, Foti, R, Visalli, E, Benenati, A, Amato, G, Ancuta, C, Villiger, P, Adler, S, Fröhlich, J, Kayser, C, Eduardo, Al, Fathi, N, Alii, S, Ahmed, M, Hasaneen, S, Hakeem, Ee, de la PG, Lefebvre, P, Martin, Jjg, Sibilia, J, Chatelus, E, Gottenberg, Je, Chifflot, H, Litinsky, I, Galdo, Fd, Abignano, G, Eng, S, Seskute, G, Butrimiene, I, Rugiene, R, Karpec, D, Pascal, M, Kerzberg, E, Bianchi, W, Bianchi, Bv, Bianchi, Dv, Barcellos, Y, Castellví, I, Millan, M, Limonta, M, Rimar, D, Rosner, I, Slobodin, G, Couto, M, Spertini, F, Ribi, C, Buss, G, Marcoccia, A, Bondanini, F, Ciani, A, Kahl, S, Hsu, Vm, Martin, T, Poindron, V, Meghit, K, Moiseev, S, Novikov, P, Chung, L, Kolstad, K, Stark, M, Schmeiser, T, Thiele, A, Majewski, D, Zdrojewski, Z, Zaneta, S, Wierzba, K, Martínez-Barrio, J, López-Longo, Fj, Bernardino, V, Moraes-Fontes, Mf, Rodrigues, Ac, Riemekasten, G, Sommerlatte, S, Jendreck, S, Arnold, S, Levy, Y, Rezus, E, Cardoneanu, A, Burlui, Am, Pamuk, On, Puttini, Ps, Talotta, R, Bongiovanni, S, Poormoghim, H, Andalib, E, Almasi, S, Kötter, I, Krusche, M, Cuomo, G, Danzo, F, Masini, F, Gaches, F, Michaud, M, Cartos, F, Belloli, L, Casu, C, Sfikakis, P, Tektonidou, M, Furst, D, Feldman, Gr, Ramazan, Am, Nurmambet, E, Miroto, A, Suta, C, Andronache, I, Huizinga, Twj, de Vries-Bouwstra, J., Chizzolini, Carlo, Jaeger, Veronika K, Tikly, Mohammed, Xu, Dong, Siegert, Elise, Hachulla, Eric, Airò, Paolo, Valentini, Gabriele, Matucci Cerinic, Marco, Distler, Oliver, Cozzi, Franco, Carreira, Patricia, Allanore, Yannick, Müller-Ladner, Ulf, Ananieva, Lidia P, Balbir-Gurman, Alexandra, Distler, Jörg H W, Czirják, Laszlo, Li, Mengtao, Henes, Jörg, Jimenez, Sergio A, Smith, Vanessa, Damjanov, Nemanja, Denton, Christopher P, Delgaldo, Francesco, Saketkoo, Lesley Ann, Walker, Ulrich A, University of Zurich, Cerinic, Marco Matucci, Walker Ulrich, A, Randone, Silvia Bellando, Bannert, Bettina, Iannone, Florenzoaa, Maurer, Brittaab, Jordan, Suzanaab, Dobrota, Rucsandraab, Becker, Mikeab, Mihai, Carinaa, Becvarare, Radima, Tomcik, Michala, Bielecka, Otylia Kowala, Gindzienska-Sieskiewicz, Ewaa, Karaszewska, Katarzynaa, Cutolo, Maurizioa, Pizzorni, Carmena, Paolino, Sabrinaae, Sulli, Albertoa, Ruaro, Barbara, Alessandri, Elisa, Riccardi, Antonella, Giacco, Veronica, Messitini, Valentina, Irace, Rosaria, Kedor, Claudia, Casteleyn, Vincent, Hilger, Julia, Hoeppner, Jakob, Rednic, Simona, Szabo, Iulia, Petcu, Ana, Avouac, Jérome, Camelia, Frantz, Desbas, Carole, Vlachoyiannopoulos, Panayioti, Montecucco, Carlo Maurizio, Caporali, Roberto, Cavagna, Lorenzo, Stork, Jiri, Inanc, Murat, Joven, Beatriz E., Novak, Srdan, Anic, Felina, Varju, Cecilia, Minier, Tunde, Allai, Daniela, Kucharz, Eugene J., Kotulska, Anna, Kopec-Medrek, Magdalena, Widuchowska, Malgorzata, Dolnicar, Alenka Sipek, Coleiro, Bernard, Gabrielli, Armando, Manfredi, Lucia, Benfaremo, Devi, Ferrarini, Alessia, Bancel, Dominique Farge, Hij, Adrian, Lazzaroni, Maria Grazia, Hesselstrand, Roger, Wuttge, Dirk, Andréasson, Kristofer, Martinovic, Duska, Bozic, Ivona, Radic, Mislav, Braun-Moscovici, Yolanda, Monaco, Andrea Lo, Furini, Federica, Hunzelmann, Nicola, Moinzadeh, Pia, Pellerito, Raffaele, Caimmi, Cristian, Bertoldo, Eugenia, Morovic-Vergles, Jadranka, Culo, Ivana Melanie, Pecher, Ann-Christian, Santamaria, Vera Ortiz, Heitmann, Stefan, Codagnone, Medeleine, Pflugfelder, Johanne, Krasowska, Dorota, Michalska-Jakubus, Malgorzata, Seidel, Matthia, Hasler, Paul, Kretschmar, Samuel, Kohm, Michaela, Bajocchi, Gianluigi, Salvador, Maria João, Da Silva, JoséAntonio Pereira, Stamenkovic, Bojana, Stankovic, Aleksandra, Selmi, Carlo Francesco, De Santis, Maria, Ceribelli, Angela, Garzanova, Ludmila, Koneva, Olga, Starovoytova, Maya, Herrick, Ariane, Puppo, Francesco, Negrini, Simone, Murdaca, Giuseppe, Engelhart, Merete, Szücs, Gabriela, Szamosi, Szilvia, De La Puente, Carlo, Grande, Cristina Sobrino, Villanueva, Maria Jesus Garcia, Midtve, Øyvindbw, Hoffmann-Vold, Anna-Mariabw, Launay, Davidbx, Sobanski, Vincentbx, Riccieri, Valeriaby, Vasile, Massimilianoby, Stefantoni, Katia, Ionescu, Ruxandra Maria, Opris, Daniela, Sha, Ami, Woods, Adrianne, Gheorghiu, Ana Maria, Bojinca, Mihai, Sunderkötter, Cord, Ehrchen, Jan, Ingegnoli, Francesca, Mouthon, Luc, Dunogue, Bertrand, Chaigne, Benjamin, Legendre, Paul, Cantatore, Francesco Paolo, Corrado, Ada, Ullman, Susanne, Iversen, Line, Von Mühlen, Carlos Alberto, Pozzi, Maria Rosa, Eyerich, Kilian, Lauffer, Felix, Wiland, Piotr, Szmyrka-Kaczmarek, Magdalena, Sokolik, Renata, Morgiel, Ewa, Madej, Marta, Vanthuyne, Marie, Frédéric, Houssiau, Alegre-Sancho, Juan Jose, Aringer, Martin, Herrmann, Kristine, Günther, Claudia, Westhovens, Rene, De Langhe, Ellen, Lenaerts, Jan, Anic, Branimir, Baresic, Marko, Mayer, Miroslav, Üprus, Maria, Otsa, Kati, Yavuz, Sule, Granel, Brigitte, Radominski, Sebastião Cezar, De Souza Müller, Carolina, Feijóazevedo, Valderílio, Mendoza, Fabian, Busquets, Joanna, Popa, Sergei, Agachi, Svetlana, Zenone, Thierry, Pileckyte, Margarita, Stebbings, Simon, Jordan, Sarah, Mathieu, Alessandro, Vacca, Alessandra, Sampaio-Barros, Percival D., Stamp, Lisa, Solanki, Kamal, Silva, Cherumi, Schollum, Joanne, Barns-Graham, Helen, Veale, Dougla, O'Rourke, Marie, Loyo, Esthela, Tineo, Carmen, Paulino, Glenny, Mohamed, Walid Ahmed Abdel Atty, Rosato, Edoardo, 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, Villiger, Peter, Adler, Sabine, Fröhlich, Johanne, Kayser, Cristiane, Eduardo, Andrade Lui, Fathi, Nihal, Alii, Safa, Ahmed, Marrow, Hasaneen, Samar, El Hakeem, Eman, De La Peña Lefebvre, Paloma García, Martin, Jorge Juan Gonzalez, Sibilia, Jean, Chatelus, Emmanuel, Gottenberg, Jacques Eric, Chifflot, Hélène, Litinsky, Ira, Del Galdo, Francesco, Abignano, Giuseppina, Eng, Sookho, Seskute, Goda, Butrimiene, Irena, Rugiene, Rita, Karpec, Diana, Pascal, Melanie, Kerzberg, Eduardo, Bianchi, Washington, Bianchi, Breno Valdetaro, Bianchi, Dante Valdetaro, Barcellos, Yeda, Castellví, Ivan, Millan, Milena, Limonta, Massimiliano, Rimar, Doron, Rosner, Itzhak, Slobodin, Gleb, Couto, Maura, Spertini, Françoi, Ribi, Camillo, Buss, Guillaume, Marcoccia, Antonella, Bondanini, Francesco, Ciani, Aldo, Kahl, Sarah, Hsu, Vivien M., Martin, Thierry, Poindron, Vincent, Meghit, Kilifa, Moiseev, Sergey, Novikov, Pavel, Chung, Lori, Kolstad, Kathleen, Stark, Marianna, Schmeiser, Tim, Thiele, Astrid, Majewski, Dominik, Zdrojewski, Zbigniew, Zaneta, Smolenska, Wierzba, Karol, Martínez-Barrio, Julia, López-Longo, Francisco Javier, Bernardino, Vera, Moraes-Fontes, Maria Francisca, Rodrigues, Ana Catarina, Riemekasten, Gabriela, Sommerlatte, Sabine, Jendreck, Sebastian, Arnold, Sabrina, Levy, Yair, Rezus, Elena, Cardoneanu, Anca, Burlui, Alexandra Maria, Pamuk, Omer Nuri, Puttini, Piercarlo Sarzi, Talotta, Rossella, Bongiovanni, Sara, Poormoghim, Hadi, Andalib, Elham, Almasi, Simin, Kötter, Ina, Krusche, Matrin, Cuomo, Giovanna, Danzo, Fiammetta, Masini, Francesco, Gaches, Franci, Michaud, Martin, Cartos, Florian, Belloli, Laura, Casu, Cinzia, Sfikakis, Petro, Tektonidou, Maria, Furst, Daniel, Feldman, Gary R., Ramazan, Ana-Maria, Nurmambet, Emel, Miroto, Amalia, Suta, Cristina, Andronache, Iulia, Huizinga, Tom W. J., De Vries-Bouwstra, Jeska, and Walker, Ulrich A.

Subjects
Male, Vital capacity, Organ manifestations, systemic sclerosis, Type I, race difference, Systemic scleroderma, Gastroenterology, Scleroderma, immunology, 0302 clinical medicine, Diffusing capacity, middle aged, pulmonary hypertension, Medicine, Pharmacology (medical), 030212 general & internal medicine, organ manifestations, races, skin and connective tissue diseases, Lung, race, pathophysiology, African Continental Ancestry Group, ddc:616, integumentary system, disease course, Hazard ratio, Races, 10051 Rheumatology Clinic and Institute of Physical Medicine, Pulmonary, Middle Aged, Blacks, cohort analysis, Autoantibodie, 3. Good health, Asians, female, priority journal, DNA Topoisomerases, Type I, Black, centromere, Cohort, Hypertension, organ manifestation, Systemic sclerosis, Female, systemic sclerosi, Human, Adult, Asian Continental Ancestry Group, medicine.medical_specialty, Hypertension, Pulmonary, European Continental Ancestry Group, Black People, 610 Medicine & health, complication, Caucasian, White People, Article, lung, 03 medical and health sciences, Black person, Rheumatology, Asian People, forced vital capacity, Internal medicine, geographic distribution, Humans, controlled study, human, DNA topoisomerase, Aged, Autoantibodies, 030203 arthritis & rheumatology, Scleroderma, Systemic, Asian, business.industry, Whites, Systemic, Odds ratio, medicine.disease, Pulmonary hypertension, major clinical study, mortality, clinical feature, business, DNA Topoisomerases, autoantibody
Abstract

Objectives Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations. Methods SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses. Results The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P < 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P < 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P < 0.001) diffuse skin involvement than had WP. AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P < 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P < 0.001; OR(BP) = 2.4, P < 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P < 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P < 0.001]. Conclusion Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality.

Published
2020

3. Outcomes of patients with systemic sclerosis treated with rituximab in contemporary practice: a prospective cohort study

Author

Elhai, M, Boubaya, M, Distler, O, Smith, V, Matucci-Cerinic, M, Sancho, JJ, Truchetet, ME, Braun-Moscovici, Y, Iannone, F, Novikov, PI, Lescoat, A, Siegert, E, Castellvi, I, Airo, P, Vettori, S, Langhe, E, Hachulla, E, Erler, A, Ananieva, L, Krusche, M, Lopez-Longo, FJ, Distler, JHW, Hunzelmann, N, Hoffmann-Vold, AM, Riccieri, V, Hsu, VM, Pozzi, MR, Ancuta, C, Rosato, E, Mihai, C, Kuwana, M, Saketkoo, LA, Chizzolini, C, Hesselstrand, R, Ullman, S, Yavuz, S, Rednic, S, Caimmi, C, Bloch-Queyrat, C, Allanore, Y, Guiducci, S, Walker, UA, Kyburz, D, Lapadula, G, Maurer, B, Jordan, S, Dobrota, R, Becvar, R, Sierakowsky, S, Bielecka, OK, Sulli, A, Cutolo, M, Cuomo, G, Nicoara, I, Kahan, A, Vlachoyiannopoulos, PG, Montecucco, CM, Caporali, R, Stork, J, Inanc, M, Carreira, PE, Novak, S, Czirjak, L, Varju, C, Kucharz, EJ, Kotulska, A, Kopec-Medrek, M, Widuchowska, M, Cozzi, F, Rozman, B, Mallia, C, Coleiro, B, Gabrielli, A, Farge, D, Wu, C, Marjanovic, Z, Faivre, H, Hij, D, Dhamadi, R, Wollheim, F, Scheja, A, Wuttge, DM, Andreasson, K, Martinovic, D, Balbir-Gurman, A, Trotta, F, Lo Monaco, A, Pellerito, R, Mauriziano, O, Caramaschi, P, Morovic-Vergles, J, Black, C, Denton, C, Damjanov, N, Henes, J, Santamaria, VO, Heitmann, S, Krasowska, D, Matthias, Hasler, P, Burkhardt, H, Himsel, A, Bajocchi, G, Da Silva, JAP, Salvador, MJ, Stamenkovic, B, Stankovic, A, Selmi, CF, De Santis, M, Tikly, M, Denisov, LN, Herrick, A, Muller-Ladner, U, Frerix, M, Tarner, I, Scorza, R, Puppo, F, Engelhart, M, Strauss, G, Nielsen, H, Damgaard, K, Szucs, G, Mendoza, AZ, de la Puente, C, Giraldo, WAS, Midtvedt, O, Reiseter, S, Garen, T, Launay, D, Valesini, G, Ionescu, RM, Groseanu, L, Opris, D, Cornateanu, RS, Ionitescu, R, Gherghe, AM, Soare, A, Gorga, M, Bojinca, M, Milicescu, M, Sunderkotter, C, Kuhn, A, Sandorfi, N, Schett, G, Beyer, C, Meroni, P, Ingegnoli, F, Mouthon, L, De Keyser, F, Melsens, K, Cantatore, FP, Corrado, A, Iversen, L, von Muhlen, CA, Bohn, JM, Lonzetti, LS, Eyerich, K, Hein, R, Knott, E, Wiland, P, Szmyrka-Kaczmarek, M, Sokolik, R, Morgiel, E, Madej, M, Houssiau, FA, Krummel-Lorenz, B, Saar, P, Aringer, M, Gunther, C, Westhovens, R, Lenaerts, J, Anic, B, Baresic, M, Mayer, M, Uprus, M, Otsa, K, Granel, B, Muller, CD, Radominski, SC, Azevedo, VF, Jimenez, S, Busquets, J, Agachi, S, Groppa, L, Chiaburu, L, Russu, E, Popa, S, Zenone, T, Pileckyte, M, Mathieu, A, Vacca, A, Sampaio-Barros, PD, Yoshinari, NH, Marangoni, RG, Martin, P, Fuocco, L, Stebbings, S, Highton, J, Chapman, P, O'Donnell, J, Stamp, L, Doube, A, Solanki, K, Veale, D, O'Rourke, M, Loyo, E, Li, MT, Mohamed, WAAA, Amoroso, A, Gigante, A, Oksel, F, Yargucu, F, Tanaseanu, CM, Popescu, M, Dumitrascu, A, Tiglea, I, Foti, R, Chirieac, R, Furst, D, Villiger, P, Adler, S, van Laar, J, Kayser, C, Fathi, N, Hassanien, M, Lefebvre, PGD, Rubio, SR, Exposito, MV, Chatelus, E, Sibilia, J, Gottenberg, JE, Chifflot, H, Litinsky, I, Emery, P, Buch, M, Del Galdo, F, Venalis, A, Butrimiene, I, Venalis, P, Rugiene, R, Karpec, D, Lasky, JA, Cosentino, V, Kerzberg, E, Montoya, F, Bianchi, W, Carneiro, S, Maretti, GB, Bianchi, DV, Limonta, M, Lupi, ALBE, Lupi, E, Rosner, I, Rozenbaum, M, Slobodin, G, Boulman, N, Rimar, D, Couto, M, Kahl, S, Chen, F, McCloskey, D, Malveaux, H, Spertini, F, Ribi, C, Buss, G, Martin, T, Guffroy, A, Poindron, V, Chotchaeva, F, Mukhin, NA, Moiseev, S, EUSTAR Network, Elhai, Muriel, Boubaya, Marouane, Distler, Oliver, Smith, Vanessa, Matucci-Cerinic, Marco, Alegre Sancho, Juan José, Truchetet, Marie-Elise, Braun-Moscovici, Yolanda, Iannone, Florenzo, Novikov, Pavel I, Lescoat, Alain, Siegert, Elise, Castellví, Ivan, Airó, Paolo, Vettori, Serena, De Langhe, Ellen, Hachulla, Eric, Erler, Anne, Ananieva, Lidia, Krusche, Martin, López-Longo, F. J., Distler, Jörg H W, Hunzelmann, Nicola, Hoffmann-Vold, Anna-Maria, Riccieri, Valeria, Hsu, Vivien M, Pozzi, Maria R, Ancuta, Codrina, Rosato, Edoardo, Mihai, Carina, Kuwana, Masataka, Saketkoo, Lesley Ann, Chizzolini, Carlo, Hesselstrand, Roger, Ullman, Susanne, Yavuz, Sule, Rednic, Simona, Caimmi, Cristian, Bloch-Queyrat, Coralie, Allanore, Yannick, and Cuomo, Giovanna

Subjects
Male, Vital capacity, systemic sclerosis, Pulmonary Fibrosis, Vital Capacity, Scleroderma, lung fibrosis, rituximab, skin fibrosis, immune system diseases, DLCO, hemic and lymphatic diseases, Immunology and Allergy, Medicine, Prospective Studies, Registries, skin and connective tissue diseases, Prospective cohort study, Lung, skin fibrosi, Skin, ddc:616, integumentary system, Orvostudományok, Middle Aged, Respiratory Function Tests, lung fibrosis, rituximab, skin fibrosis, systemic sclerosis, Treatment Outcome, lung fibrosi, Antirheumatic Agents, Systemic sclerosis, Rituximab, Female, systemic sclerosi, medicine.drug, Adult, medicine.medical_specialty, Immunology, Klinikai orvostudományok, General Biochemistry, Genetics and Molecular Biology, FEV1/FVC ratio, Rheumatology, Internal medicine, Humans, Adverse effect, Propensity Score, Aged, Biochemistry, Genetics and Molecular Biology (all), Scleroderma, Systemic, Skin fibrosis, business.industry, medicine.disease, Fibrosis, Lung fibrosis, business
Abstract

ObjectiveTo assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice.MethodsWe performed a prospective study including patients with SSc from the European Scleroderma Trials and Research (EUSTAR) network treated with rituximab and matched with untreated patients with SSc. The main outcomes measures were adverse events, skin fibrosis improvement, lung fibrosis worsening and steroids use among propensity score-matched patients treated or not with rituximab.Results254 patients were treated with rituximab, in 58% for lung and in 32% for skin involvement. After a median follow-up of 2 years, about 70% of the patients had no side effect. Comparison of treated patients with 9575 propensity-score matched patients showed that patients treated with rituximab were more likely to have skin fibrosis improvement (22.7 vs 14.03 events per 100 person-years; OR: 2.79 [1.47–5.32]; p=0.002). Treated patients did not have significantly different rates of decrease in forced vital capacity (FVC)>10% (OR: 1.03 [0.55–1.94]; p=0.93) nor in carbon monoxide diffusing capacity (DLCO) decrease. Patients having received rituximab were more prone to stop or decrease steroids (OR: 2.34 [1.56–3.53], pConclusionRituximab use was associated with a good safety profile in this large SSc-cohort. Significant change was observed on skin fibrosis, but not on lung. However, the limitation is the observational design. The potential stabilisation of lung fibrosis by rituximab has to be addressed by a randomised trial.

Published
2019

4. 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

Author

Wu, Wanlong, Jordan, Suzana, Graf, Nicole, Pena, Janethe de Oliveira, 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, Czirjak, Laszlo, Varju, Cecilia, Chizzolini, Carlo, Allai, Daniela, Kucharz, Eugene J., Cozzi, Franco, Rozman, Blaz, Mallia, Carmel, Gabrielli, Armando, Bancel, Dominique Farge, Airo, Paolo, Hesselstrand, Roger, Martinovic, Duska, Balbir-Gurman, Alexandra, Braun-Moscovici, Yolanda, Hunzelmann, Nicolas, Pellerito, Raffaele, Caramaschi, Paola, Black, Carol, Damjanov, Nemanja, Henes, Joerg, Ortiz Santamaria, Vera, Heitmann, Stefan, Seidel, Matthias, Pereira Da Silva, Jose Antonio, Stamenkovic, Bojana, Selmi, Carlo Francesco, Tikly, Mohammed, Denisov, Lev N., Mueller-Ladner, Ulf, Engelhart, Merete, Hachulla, Eric, Riccieri, Valeria, Ionescu, Ruxandra Maria, Mihai, Carina, Sunderkoetter, Cord, Kuhn, Annegret, Schett, Georg, Distler, Joerg, 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, Ruediger, Knott, Elisabeth, Wiland, Piotr, Szmyrka-Kaczmarek, Magdalena, Sokolik, Renata, Morgiel, Ewa, Madej, Marta, Jose Alegre-Sancho, Juan, Krummel-Lorenz, Brigitte, Saar, Petra, Aringer, Martin, Guenther, Claudia, Anne, Erler, Westhovens, Rene, De Langhe, Ellen, Lenaerts, Jan, Anic, Branimir, Baresic, Marko, Mayer, Miroslav, Uprus, Maria, Otsa, Kati, Yavuz, Sule, Radominski, Sebastiao Cezar, Mueller, Carolina de Souza, Azevedo, Valderilio Feijo, 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 Pena Lefebvre, Paloma Garcia, Rodriguez Rubio, Silvia, Valero Exposito, Marta, Sibilia, Jean, Chatelus, Emmanuel, Gottenberg, Jacques Eric, Chifflot, Helene, 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, Francois, Ribi, Camillo, Buss, Guillaume, Martin, Thierry, Guffroy, Aurelien, Poindron, Vincent, Chung, Lori, Schmeiser, Tim, Zebryk, Pawel, Riso, Nuno, Riemekasten, Gabriela, Rezus, Elena, Puttini, Piercarlo Sarzi, 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. -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., 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., Ege Üniversitesi, Chizzolini, Carlo, Allali, Danièle, University of Zurich, and Distler, Oliver

Subjects
INVOLVEMENT, Male, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences, diffuse, Time Factors, Databases, Factual, Skin Diseases/etiology/mortality/physiopathology, PREDICTION, Fibrosi, 2745 Rheumatology, Diffuse/complications/mortality/pathology, Immunology, General Biochemistry, Genetics and Molecular Biology, Immunology and Allergy, Rheumatology, Kaplan-Meier Estimate, ddc:616.07, Severity of Illness Index, Scleroderma, Cohort Studies, PROGNOSTIC-FACTORS, Fibrosis, Medicine and Health Sciences, scleroderma, Lung, Skin, integumentary system, progressive skin fibrosis, Lung function decline, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti, 10051 Rheumatology Clinic and Institute of Physical Medicine, DEATH, Middle Aged, ddc, Europe, VARIABILITY, factual, Cohort, Visceral organ progression, 2723 Immunology and Allergy, Disease Progression, Female, Survival Analysi, Life Sciences & Biomedicine, Cohort study, Human, Adult, Skin/pathology, medicine.medical_specialty, databases, All-cause death, risk analysis, diffuse cutaneous systemic sclerosis, 610 Medicine & health, IMPROVEMENT, Systemic Sclerosis, Skin Diseases, THICKNESS SCORE, VALIDATION, Databases, FEV1/FVC ratio, 1300 General Biochemistry, Genetics and Molecular Biology, Internal medicine, medicine, Humans, Factual, Survival analysis, 2403 Immunology, Science & Technology, Proportional hazards model, business.industry, Surrogate endpoint, MORTALITY, Skin Disease, fibrosis, Progressive skin fibrosi, Lung/physiopathology, biomarkers, Diffuse cutaneous systemic sclerosi, medicine.disease, Survival Analysis, all-cause death, lung function decline, visceral organ progression, adult, cohort studies, databases, factual, disease progression, female, humans, Scleroderma, Diffuse, Cohort Studie, business
Abstract

PubMed: 30852552, 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, Bayer Bayer, 1Department of Rheumatology, University Hospital Zurich, Zurich, switzerland 2Graf Biostatistics, Winterthur, switzerland 3Clinical Development Pulmonology, Bayer Us llC, Whippany, new Jersey, Usa 4Data science and analytics, Bayer plc, Reading, UK 5Rheumatology a Department, Paris Descartes University, inseRM U1016, sorbonne, Paris Cité, Cochin Hospital, Paris, France 6Division of Rheumatology, University of Florence, Florence, italy 7Department of Medicine, Division of Rheumatology, University of Western Ontario, st. Joseph’s Health Care, london, Western Ontario, Canada 8Department of Rheumatology, Royal Free Hospital, University College london, london, UK 9scleroderma Program, Department of internal Medicine, Division of Rheumatology, University of Michigan, ann arbor, Michigan, Usa Acknowledgements The authors thank nicole schneider for excellent administration and data entry into the eUsTaR cohort. Medical writing assistance was provided by adelphi Communications ltd (Bollington, UK), funded by Bayer aG (Berlin, Germany)., This study was supported by a grant from Bayer aG.

Published
2019

5. Phenotypes determined by cluster analysis and their survival in the prospective European Scleroderma Trials and Research cohort of patients with systemic sclerosis

Author

Sobanski, Vincent, Giovannelli, Jonathan, Allanore, Yannick, Riemekasten, Gabriela, Airo, Paolo, Vettori, Serena, Cozzi, Franco, Distler, Oliver, Matucci-Cerinic, Marco, Denton, Christopher, Launay, David, Hachulla, Eric, Cerinic, Marco Matucci, Guiducci, Serena, Walker, Ulrich, Kyburz, Diego, Lapadula, Giovanni, Iannone, Florenzo, Maurer, Britta, Jordan, Suzana, Becvar, Radim, Sierakowsky, Stanislaw, Bielecka, Otylia Kowal, Cutolo, Maurizio, Sulli, Alberto, Valentini, Gabriele, Cuomo, Giovanna, Siegert, Elise, Rednic, Simona, Nicoara, Ileana, Kahan, Andre, Vlachoyiannopoulos, Panayiotis, Montecucco, Carlo, Caporali, Roberto, Stork, Jiri, Inanc, Murat, Carreira, Patricia E, Novak, Srdan, Czirjak, Laszlo, Varju, Cecilia, Chizzolini, Carlo, Kucharz, Eugene J, Kotulska, Anna, Kopec-Medrek, Magdalena, Widuchowska, Malgorzata, Rozman, Blaz, Mallia, Carmel, Coleiro, Bernard, Gabrielli, Armando, Farge, Dominique, Wu, Chen, Marjanovic, Zora, Faivre, Helene, Hij, Darin, Dhamadi, Roza, Hesselstrand, Roger, Wollheim, Frank, Wuttge, Dirk M, Andreasson, Kristofer, Martinovic, Duska, Balbir-Gurman, Alexandra, Braun-Moscovici, Yolanda, Trotta, Francesco, Lo Monaco, Andrea, Hunzelmann, Nicolas, Pellerito, Raffaele, Bambara, Lisa Maria, Caramaschi, Paola, Morovic-Vergles, Jadranka, Black, Carol, Damjanov, Nemanja, Henes, Joerg, Ortiz Santamaria, Vera, Heitmann, Stefan, Krasowska, Dorota, Seidel, Matthias, Hasler, Paul, Burkhardt, Harald, Himsel, Andrea, Bajocchi, Gianluigi, Nuova, Arcispedale Santa Maria, Salvador, Maria Joao, Pereira Da Silva, Jose Antonio, Stamenkovic, Bojana, Stankovic, Aleksandra, Selmi, Carlo Francesco, De Santis, Maria, Marasini, Bianca, Tikly, Mohammed, Ananieva, Lidia P, Denisov, Lev N, Mueller-Ladner, Ulf, Frerix, Marc, Tarner, Ingo, Scorza, Raffaella, Puppo, Francesco, Engelhart, Merete, Strauss, Gitte, Nielsen, Henrik, Damgaard, Kirsten, Szucs, Gabriella, Szamosi, Szilvia, Zea Mendoza, Antonio, de la Puente, Carlos, Sifuentes Giraldo, Walter Alberto, Midtvedt, Oyvind, Reiseter, Silje, Garen, Torhild, Valesini, Guido, Riccieri, Valeria, Ionescu, Ruxandra Maria, Opris, Daniela, Groseanu, Laura, Wigley, Fredrick M, Cornateanu, Roxana Sfrent, Ionitescu, Razvan, Gherghe, Ana Maria, Soare, Alina, Gorga, Marilena, Bojinca, Mihai, Mihai, Carina, Milicescu, Mihaela, Sunderkoetter, Cord, Kuhn, Annegret, Sandorfi, Nora, Schett, Georg, Distler, Joerg HW, Beyer, Christian, Meroni, Pierluigi, Ingegnoli, Francesca, Mouthon, Luc, De Keyser, Filip, Smith, Vanessa, Cantatore, Francesco Paolo, Corrado, Ada, Ullman, Susanne, Iversen, Line, von Muehlen, Carlos Alberto, Bohn, Jussara Marilu, Lonzetti, Lilian Scussel, Pozzi, Maria Rosa, Eyerich, Kilian, Hein, Ruediger, Knott, Elisabeth, Wiland, Piotr, Szmyrka-Kaczmarek, Magdalena, Sokolik, Renata, Morgiel, Ewa, Madej, Marta, Houssiau, Frederic A, Jose Alegre-Sancho, Juan, Krummel-Lorenz, Brigitte, Saar, Petra, Aringer, Martin, Guenther, Claudia, Westhovens, Rene, de Langhe, Ellen, Lenaerts, Jan, Anic, Branimir, Baresic, Marko, Mayer, Miroslav, Uprus, Maria, Otsa, Kati, Yavuz, Sule, Granel, Brigitte, Radominski, Sebastiao Cezar, Mueller, Carolina de Souza, Azevedo, Valderilio Feijo, Jimenez, Sergio, Busquets, Joanna, Agachi, Svetlana, Groppa, Liliana, Chiaburu, Lealea, Russu, Eugen, Popa, Sergei, Zenone, Thierry, Pileckyte, Margarita, Stebbings, Simon, Highton, John, Mathieu, Alessandro, Vacca, Alessandra, Sampaio-Barros, Percival D, Yoshinari, Natalino H, Marangoni, Roberta G, Martin, Patricia, Fuocco, Luiza, Stamp, Lisa, Chapman, Peter, O'Donnell, John, Solanki, Kamal, Doube, Alan, Veale, Douglas, O'Rourke, Marie, Loyo, Esthela, Li, Mengtao, Mohamed, Walid Ahmed Abdel Atty, Rosato, Edoardo, Amoroso, Antonio, Gigante, Antonietta, Oksel, Fahrettin, Yargucu, Figen, Tanaseanu, Cristina-Mihaela, Popescu, Monica, Dumitrascu, Alina, Tiglea, Isabela, Foti, Rosario, Chirieac, Rodica, Ancuta, Codrina, Furst, Daniel E, Villiger, Peter, Adler, Sabine, van Laar, Jacob, Kayser, Cristiane, Eduardo, Andrade Luis C, Fathi, Nihal, Hassanien, Manal, de la Pena Lefebvre, Paloma Garcia, Rodriguez Rubio, Silvia, Valero Exposito, Marta, Sibilia, Jean, Chatelus, Emmanuel, Gottenberg, Jacques Eric, Chifflot, Helene, Litinsky, Ira, Emery, Paul, Buch, Maya, Del Galdo, Francesco, Venalis, Algirdas, Butrimiene, Irena, Venalis, Paulius, Rugiene, Rita, Karpec, Diana, Saketkoo, Lesley Ann, Lasky, Joseph A, Kerzberg, Eduardo, Montoya, Fabiana, Cosentino, Vanesa, Limonta, Massimiliano, Brucato, Antonio Luca, Lupi, Elide, Rosner, Itzhak, Rozenbaum, Michael, Slobodin, Gleb, Boulman, Nina, Rimar, Doron, Couto, Maura, Spertini, Francois, Ribi, Camillo, Buss, Guillaume, Kahl, Sarah, Hsu, Vivien M, Chen, Fei, McCloskey, Deborah, Malveaux, Halina, Pasquali, Jean Louis, Martin, Thierry, Gorse, Audrey, Guffroy, Aurelien, Poindron, Vincent, EUSTAR Collaborators, Guiducci, S., Walker, U., Kyburz, D., Lapadula, G., Iannone, F., Maurer, B., Jordan, S., Becvar, R., Sierakowsky, S., Kowal Bielecka, O., Cutolo, M., Sulli, A., Valentini, G., Cuomo, G., Siegert, E., Rednic, S., Nicoara, I., Kahan, A., Vlachoyiannopoulos, P., Montecucco, C., Caporali, R., Stork, J., Inanc, M., Carreira, P.E., Novak, S., Czirják, L., Varju, C., Chizzolini, C., Kucharz, E.J., Kotulska, A., Kopec-Medrek, M., Widuchowska, M., Rozman, B., Mallia, C., Coleiro, B., Gabrielli, A., Farge, D., Wu, C., Marjanovic, Z., Faivre, H., Hij, D., Dhamadi, R., Airò, P., Hesselstrand, R., Wollheim, F., Wuttge, D.M., Andréasson, K., Martinovic, D., Balbir-Gurman, A., Braun-Moscovici, Y., Trotta, F., Lo Monaco, A., Hunzelmann, N., Pellerito, R., Mauriziano, O., Maria Bambara, L., Caramaschi, P., Morovic-Vergles, J., Black, C., Damjanov, N., Henes, J., Ortiz Santamaria, V., Heitmann, S., Krasowska, D., Seidel, M., Hasler, P., Burkhardt, H., Himsel, A., Bajocchi, G., Maria Nuova, A.S., João Salvador, M., Pereira Da Silva, J.A., Stamenkovic, B., Stankovic, A., Francesco Selmi, C., De Santis, M., Marasini, B., Tikly, M., Ananieva, L.P., Denisov, L.N., Müller-Ladner, U., Frerix, M., Tarner, I., Scorza, R., Puppo, F., Engelhart, M., Strauss, G., Nielsen, H., Damgaard, K., Szücs, G., Szamosi, S., Zea Mendoza, A., de la Puente, C., Sifuentes Giraldo, W.A., Midtvedt, Ø., Reiseter, S., Garen, T., Valesini, G., Riccieri, V., Maria Ionescu, R., Opris, D., Groseanu, L., Wigley, F.M., Sfrent Cornateanu, R., Ionitescu, R., Maria Gherghe, A., Soare, A., Gorga, M., Bojinca, M., Mihai, C., Milicescu, M., Sunderkötter, C., Kuhn, A., Sandorfi, N., Schett, G., Distler, J.H., Beyer, C., Meroni, P., Ingegnoli, F., Mouthon, L., De Keyser, F., Smith, V., Paolo Cantatore, F., Corrado, A., Ullman, S., Iversen, L., Alberto von Mühlen, C., Marilu Bohn, J., Scussel Lonzetti, L., Rosa Pozzi, M., Eyerich, K., Hein, R., Knott, E., Wiland, P., Szmyrka-Kaczmarek, M., Sokolik, R., Morgiel, E., Madej, M., Houssiau, F.A., Jose Alegre-Sancho, J., Krummel-Lorenz, B., Saar, P., Aringer, M., Günther, C., Westhovens, R., de Langhe, E., Lenaerts, J., Anic, B., Baresic, M., Mayer, M., Üprus, M., Otsa, K., Yavuz, S., Granel, B., Cezar Radominski, S., de Souza Müller, C., Azevedo, V.F., Jimenez, S., Busquets, J., Agachi, S., Groppa, L., Chiaburu, L., Russu, E., Popa, S., Zenone, T., Pileckyte, M., Stebbings, S., Highton, J., Mathieu, A., Vacca, A., Sampaio-Barros, P.D., Yoshinari, N.H., Marangoni, R.G., Martin, P., Fuocco, L., Stamp, L., Chapman, P., O'Donnell, J., Solanki, K., Doube, A., Veale, D., O'Rourke, M., Loyo, E., Li, M., Abdel Atty Mohamed, W.A., Rosato, E., Amoroso, A., Gigante, A., Oksel, F., Yargucu, F., Tanaseanu, C.M., Popescu, M., Dumitrascu, A., Tiglea, I., Foti, R., Chirieac, R., Ancuta, C., Furst, D.E., Villiger, P., Adler, S., van Laar, J., Kayser, C., Eduardo C, A.L., Fathi, N., Hassanien, M., de la Peña Lefebvre, P.G., Rodriguez Rubio, S., Valero Exposito, M., Sibilia, J., Chatelus, E., Gottenberg, J.E., Chifflot, H., Litinsky, I., Emery, P., Buch, M., Del Galdo, F., Venalis, A., Butrimiene, I., Venalis, P., Rugiene, R., Karpec, D., Ann Saketkoo, L., Lasky, J.A., Kerzberg, E., Montoya, F., Cosentino, V., Limonta, M., Luca Brucato, A., Lupi, E., Rosner, I., Rozenbaum, M., Slobodin, G., Boulman, N., Rimar, D., Couto, M., Spertini, F., Ribi, C., Buss, G., Kahl, S., Hsu, V.M., Chen, F., McCloskey, D., Malveaux, H., Louis Pasquali, J., Martin, T., Gorse, A., Guffroy, A., Poindron, V., and Chizzolini, Carlo

Subjects
0301 basic medicine, Male, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences, Databases, Factual, systemic sclerosis, SUBSETS, Disease, Severity of Illness Index, Scleroderma, DISEASE, 0302 clinical medicine, Medicine and Health Sciences, Immunology and Allergy, Cluster Analysis, CRITERIA, Prospective Studies, Prospective cohort study, skin and connective tissue diseases, integumentary system, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti, Adult, Aged, Autoantibodies/blood, Europe/epidemiology, Female, Humans, Middle Aged, Phenotype, Prognosis, Scleroderma, Diffuse/blood, Scleroderma, Diffuse/epidemiology, Scleroderma, Diffuse/pathology, Scleroderma, Limited/blood, Scleroderma, Limited/epidemiology, Scleroderma, Limited/pathology, Scleroderma, Systemic/blood, Scleroderma, Systemic/epidemiology, Scleroderma, Systemic/pathology, Connective tissue disease, ddc, Europe, MANIFESTATIONS, Cohort, Life Sciences & Biomedicine, medicine.medical_specialty, Immunology, PROFILE, CLASSIFICATION, 03 medical and health sciences, Rheumatology, Scleroderma, Limited, Internal medicine, Severity of illness, medicine, Autoantibodies, 030203 arthritis & rheumatology, Science & Technology, Scleroderma, Systemic, business.industry, Autoantibody, Systemic sclerosis (SSc), medicine.disease, 030104 developmental biology, Scleroderma, Diffuse, business
Abstract

OBJECTIVE: Systemic sclerosis (SSc) is a heterogeneous connective tissue disease that is typically subdivided into limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) depending on the extent of skin involvement. This subclassification may not capture the entire variability of clinical phenotypes. The European Scleroderma Trials and Research (EUSTAR) database includes data on a prospective cohort of SSc patients from 122 European referral centers. This study was undertaken to perform a cluster analysis of EUSTAR data to distinguish and characterize homogeneous phenotypes without any a priori assumptions, and to examine survival among the clusters obtained. METHODS: A total of 11,318 patients were registered in the EUSTAR database, and 6,927 were included in the study. Twenty-four clinical and serologic variables were used for clustering. RESULTS: Clustering analyses provided a first delineation of 2 clusters showing moderate stability. In an exploratory attempt, we further characterized 6 homogeneous groups that differed with regard to their clinical features, autoantibody profile, and mortality. Some groups resembled usual dcSSc or lcSSc prototypes, but others exhibited unique features, such as a majority of lcSSc patients with a high rate of visceral damage and antitopoisomerase antibodies. Prognosis varied among groups and the presence of organ damage markedly impacted survival regardless of cutaneous involvement. CONCLUSION: Our findings suggest that restricting subsets of SSc patients to only those based on cutaneous involvement may not capture the complete heterogeneity of the disease. Organ damage and antibody profile should be taken into consideration when individuating homogeneous groups of patients with a distinct prognosis. ispartof: ARTHRITIS & RHEUMATOLOGY vol:71 issue:9 pages:1553-1570 ispartof: location:United States status: published

Published
2019

6. Predictors of disease worsening defined by progression of organ damage in diffuse systemic sclerosis: A European Scleroderma Trials and Research (EUSTAR) analysis

Author

Becker, Mike, Graf, Nicole, Sauter, Rafael, Allanore, Yannick, Curram, John, Denton, Christopher P., Khanna, Dinesh, Matucci-Cerinic, Marco, Pena, Janethe de Oliveira, Pope, Janet E., 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, Czirjak, Laszlo, Varju, Cecilia, Chizzolini, Carlo, Allai, Daniela, Kucharz, Eugene J., Cozzi, Franco, Rozman, Blaz, Mallia, Carmel, Gabrielli, Armando, Bancel, Dominique Farge, Airo, Paolo, Hesselstrand, Roger, Martinovic, Duska, Balbir-Gurman, Alexandra, Braun-Moscovici, Yolanda, Hunzelmann, Nicolas, Pellerito, Raffaele, Caramaschi, Paola, Black, Carol, Damjanov, Nemanja, Henes, Joerg, Ortiz Santamaria, Vera, Heitmann, Stefan, Seidel, Matthias, Pereira Da Silva, Jose Antonio, Stamenkovic, Bojana, Selmi, Carlo Francesco, Tikly, Mohammed, Denisov, Lev N., Mueller-Ladner, Ulf, Engelhart, Merete, Hachulla, Eric, Riccieri, Valeria, Ionescu, Ruxandra Maria, Mihai, Carina, Sunderkoetter, Cord, Kuhn, Annegret, Schett, Georg, Distler, Joerg, 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, Ruediger, Knott, Elisabeth, Wiland, Piotr, Szmyrka-Kaczmarek, Magdalena, Sokolik, Renata, Morgiel, Ewa, Madej, Marta, Jose Alegre-Sancho, Juan, Krummel-Lorenz, Brigitte, Saar, Petra, Aringer, Martin, Guenther, Claudia, Anne, Erler, Westhovens, Rene, De langhe, Ellen, Lenaerts, Jan, Anic, Branimir, Baresic, Marko, Mayer, Miroslav, Uprus, Maria, Otsa, Kati, Yavuz, Sule, Radominski, Sebastiao Cezar, Mueller, Carolina de Souza, Azevedo, Valderilio Feijo, 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 Pena Lefebvre, Paloma Garcia, Rodriguez Rubio, Silvia, Valero Exposito, Marta, Sibilia, Jean, Chatelus, Emmanuel, Gottenberg, Jacques Eric, Chifflot, Helene, 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, Francois, Ribi, Camillo, Buss, Guillaume, Martin, Thierry, Guffroy, Aurelien, Poindron, Vincent, Chung, Lori, Schmeiser, Tim, Zebryk, Pawel, Riso, Nuno, Riemekasten, Gabriela, Rezus, Elena, Puttini, Piercarlo Sarzi, Ege Üniversitesi, University of Zurich, Distler, Oliver, Chizzolini, Carlo, Allai, Daniela, Becker, M., Graf, N., Sauter, R., Allanore, Y., Curram, J., Denton, C. P., Khanna, D., Matucci-Cerinic, M., de Oliveira Pena, J., Pope, J. E., 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. -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., 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., and Sarzi Puttini, P.

Subjects
INVOLVEMENT, SELECTION, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences, diffuse, predictive factors, systemic sclerosis, 2745 Rheumatology, epidemiologic methods, morbidity, Disease, Immunology, General Biochemistry, Genetics and Molecular Biology, Immunology and Allergy, Rheumatology, INTERSTITIAL LUNG-DISEASE, disease worsening, mortality, predictive factors, systemic sclerosis, predictive factor, disease worsening, DESIGN, middle aged, Medicine and Health Sciences, FIBROSIS, scleroderma, SKIN THICKNESS SCORE, mortality, skin and connective tissue diseases, Prospective cohort study, humans, lung diseases, ddc:616, education.field_of_study, heart diseases, integumentary system, clinical trials as topic, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti, 10051 Rheumatology Clinic and Institute of Physical Medicine, Interstitial lung disease, follow-up studies, ddc, female, Cohort, 2723 Immunology and Allergy, europe, Life Sciences & Biomedicine, CLINICAL-TRIALS, survival rate, medicine.medical_specialty, Population, 610 Medicine & health, disease progression, male, 1300 General Biochemistry, Genetics and Molecular Biology, Internal medicine, Severity of illness, REGRESSION, medicine, severity of illness index, education, Survival rate, METAANALYSIS, 2403 Immunology, Science & Technology, Scleroderma, Systemic, business.industry, MORTALITY, systemic, medicine.disease, prospective studies, Clinical trial, prognosis, scleroderma, diffuse, scleroderma, systemic, Scleroderma, Diffuse, business
Abstract

PubMed: 31227488, Objectives Mortality and worsening of organ function are desirable endpoints for clinical trials in systemic sclerosis (SSc). The aim of this study was to identify factors that allow enrichment of patients with these endpoints, in a population of patients from the European Scleroderma Trials and Research group database. Methods Inclusion criteria were diagnosis of diffuse SSc and follow-up over 12±3 months. Disease worsening/organ progression was fulfilled if any of the following events occurred: new renal crisis; decrease of lung or heart function; new echocardiography-suspected pulmonary hypertension or death. In total, 42 clinical parameters were chosen as predictors for the analysis by using (1) imputation of missing data on the basis of multivariate imputation and (2) least absolute shrinkage and selection operator regression. Results Of 1451 patients meeting the inclusion criteria, 706 had complete data on outcome parameters and were included in the analysis. Of the 42 outcome predictors, eight remained in the final regression model. There was substantial evidence for a strong association between disease progression and age, active digital ulcer (DU), lung fibrosis, muscle weakness and elevated C-reactive protein (CRP) level. Active DU, CRP elevation, lung fibrosis and muscle weakness were also associated with a significantly shorter time to disease progression. A bootstrap validation step with 10 000 repetitions successfully validated the model. Conclusions The use of the predictive factors presented here could enable cohort enrichment with patients at risk for overall disease worsening in SSc clinical trials. © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ., Bayer Bayer, United Kingdom Université Paris Descartes Li Ka Shing Foundation, LKSF University of Michigan, U-M, 1Department of Rheumatology and the Centre of experimental Rheumatology, University Hospital Zurich, Zurich, switzerland 2Graf Biostatistics, Winterthur, switzerland 3Big Data institute, li Ka shing Centre for Health information and Discovery, nuffield Department of Medicine, University of Oxford, Oxford, UK 4Rheumatology a Department, Paris Descartes University, sorbonne Paris Cité, Cochin Hospital, Paris, France 5Data science and analytics, Bayer plc, Reading, UK 6UCl Division of Medicine, Royal Free Campus, london, UK 7Division of Rheumatology, Department of internal Medicine, University of Michigan scleroderma Program, University of Michigan, ann arbor, Michigan, Usa 8Department of experimental and Clinical Medicine, University of Florence, Florence, italy 9Bayer Us llC, Whippany, new Jersey, Usa 10Department of Medicine, Division of Rheumatology, University of Western Ontario, st. Joseph’s Health Care, london, Ontario, Canada Acknowledgements The R-code for the linear Mi-lassO was received from Qixuan Chen.21 Medical writing assistance was provided by adelphi Communications ltd (Bollington, UK), funded by Bayer aG (Berlin, Germany)., Contributors study conception and design, acquisition of data, analysis and interpretation of data and drafting and revising the article: OD and MB; analysis and interpretation of data: OD, MB, Rs and nG. all authors have critically reviewed and approved the final submitted version to be published. Funding This study was supported by a grant from Bayer aG. Bayer employees are coauthors of this paper and supported the study design and interpretation of the data, but otherwise Bayer had no influence on the study., Competing interests MOB declares no conflict of interest. OD has had consultancy relationships with actelion, Bayer, Biogen idec, Boehringer ingelheim, Chemomab, espeRare foundation, Genentech/Roche, GsK, inventiva, italfarmaco, lilly, medac, Medimmune, Mitsubishi Tanabe Pharma, Pharmacyclics, novartis, Pfizer, sanofi, sinoxa and UCB in the area of potential treatments of scleroderma and its complications. OD has received research funding from actelion, Bayer, Boehringer ingelheim, Mitsubishi Tanabe Pharma and Roche in the area of potential treatments of scleroderma and its complications. OD has a patent for mir-29 licensed for the treatment of systemic sclerosis. DK has consultancy relationships and/or has received grant/research support from Bayer, Bristol-Myers squibb, Boehringer ingelheim, Genentech/Roche, niH, Pfizer, sanofi-aventis Pharmaceuticals, actelion Pharmaceuticals Us, Chemomab, Corbus, Covis, Cytori, eicos, eMD serono, Gilead, GlaxosmithKline, and UCB Pharma. He is a shareholder of eicos. CPD has consultancy relationships with and/or has received speakers’ bureau fees from actelion Pharmaceuticals Us, Bayer aG, GlaxosmithKline, Csl Behring, Merck serono, Roche Pharmaceuticals, Genentech and Biogen iDeC inc., inventiva, sanofi-aventis Pharmaceuticals and Boehringer ingelheim. JeP has consultancy relationships with and/or has received grant/research support from actelion, Bayer aG, Bristol-Myers squibb, Merck, Pfizer inc. and Roche. MM-C has consultancy relationships and/ or has received grant/research support from Pfizer, Bristol-Myers squibb, actelion, UCB Pharma, Bayer, Chemomab, Genentech/Roche, inventiva and lilly. Ya has consultancy relationships with and/or has received grant/research support from actelion, Pharmaceuticals Us, Bayer aG, Bristol-Myers squibb, inventiva, Medac, Pfizer inc., Roche Pharmaceuticals, Genentech and Biogen iDeC inc., sanofi-aventis Pharmaceuticals and servier. JdOP and JC are employees of Bayer. nTG has nothing to disclose.

Published
2019

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