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1. Does the Impact of COVID‐19 on Patients With Systemic Sclerosis Change Over Time?

Author

Deibel, Elisabeth, Carreira, Patricia E., Vonk, Madelon, del Papa, Nicoletta, Bečvář, Radim, Guillén‐Del‐Castillo, Alfredo, Campochiaro, Corrado, Poormoghim, Hadi, Liem, Sophie, Lazzaroni, Maria‐Grazia, Giollo, Alessandro, Mekinian, Arsène, de Vries‐Bouwstra, Jeska, De Santis, Maria, Balbir‐Gurman, Alexandra, Mihai, Carina, De Luca, Giacomo, Moiseev, Sergey, Zanatta, Elisabetta, Foti, Rosario, Rednic, Simona, Denton, Christopher, Cutolo, Maurizio, Belloli, Laura, Airo, Paolo, Garzanova, Liudmila, Moroncini, Gianluca, İnanç, Murat, Panopoulos, Stylianos, Tandaipan, Jose‐Luis, Chatelus, Emmanuel, Rosato, Edoardo, Kuwana, Masataka, Yavuz, Sule, Alegre‐Sancho, Juan J., Smith, Vanessa, Szűcs, Gabriella, Henes, Joerg, Rodríguez‐Pintó, Ignasi, Atzeni, Fabiola, Spierings, Julia, Truchetet, Marie‐Elise, Milchert, Marcin, Brito de Araujo, Daniel, Riemekasten, Gabriela, Bernardino, Vera, Martin, Thierry, del Galdo, Francesco, Vacca, Alessandra, Mendoza, Fabian, Midtvedt, Øyvind, Murdaca, Giuseppe, Santiago, Tânia, Codullo, Veronica, Cacciapaglia, Fabio, Walker, Ulrich, Brunborg, Cathrine, Tirelli, Francesca, Allanore, Yannick, Furst, Daniel E., Matucci, Marco, Gabrielli, Armando, Distler, Oliver, and Hoffmann‐Vold, Anna‐Maria

Published
2024
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2. Recomendaciones SER sobre prevención de infección en enfermedades reumáticas autoinmunes sistémicas

Author

Rúa-Figueroa Fernández de Larrinoa, Íñigo, Carreira, Patricia E., Brito García, Noé, Díaz del Campo Fontecha, Petra, Pego Reigosa, José María, Gómez Puerta, José A., Ortega-Castro, Rafaela, Tejera Segura, Beatriz, Aguado García, José María, Torre-Cisneros, Julián, Valencia-Martín, José L., Pereda, Claudia Alejandra, Nishishinya-Aquino, María Betina, Otón Sánchez, María Teresa, Silva Fernández, Lucía, Maese Manzano, Jesús, Chamizo Carmona, Eugenio, and Correyero Plaza, María

Published
2022
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4. Does the impact of COVID-19 on patients with systemic sclerosis change over time?

Author

MS Reumatologie/Immunologie/Infectie, Infection & Immunity, Deibel, Elisabeth, Carreira, Patricia E, Vonk, Madelon, Del Papa, Nicoletta, Bečvář, Radim, Guillén-Del-Castillo, Alfredo, Campochiaro, Corrado, Poormoghim, Hadi, Liem, Sophie, Lazzaroni, Maria-Grazia, Giollo, Alessandro, Mekinian, Arsène, de Vries-Bouwstra, Jeska, De Santis, Maria, Balbir-Gurman, Alexandra, Mihai, Carina, De Luca, Giacomo, Moiseev, Sergey, Zanatta, Elisabetta, Foti, Rosario, Rednic, Simona, Denton, Christopher, Cutolo, Maurizio, Belloli, Laura, Airo, Paolo, Garzanova, Liudmila, Moroncini, Gianluca, İnanç, Murat, Panopoulos, Stylianos, Tandaipan, Jose-Luis, Chatelus, Emmanuel, Rosato, Edoardo, Kuwana, Masataka, Yavuz, Sule, Alegre-Sancho, Juan J, Smith, Vanessa, Szűcs, Gabriella, Henes, Joerg, Rodríguez-Pintó, Ignasi, Atzeni, Fabiola, Spierings, Julia, Truchetet, Marie-Elise, Milchert, Marcin, Brito de Araujo, Daniel, Riemekasten, Gabriela, Bernardino, Vera, Martin, Thierry, Del Galdo, Francesco, Vacca, Alessandra, Mendoza, Fabian, Midtvedt, Øyvind, Murdaca, Giuseppe, Santiago, Tânia, Codullo, Veronica, Cacciapaglia, Fabio, Walker, Ulrich, Brunborg, Cathrine, Tirelli, Francesca, Allanore, Yannick, Furst, Daniel E, Matucci, Marco, Gabrielli, Armando, Distler, Oliver, Hoffmann-Vold, Anna-Maria, MS Reumatologie/Immunologie/Infectie, Infection & Immunity, Deibel, Elisabeth, Carreira, Patricia E, Vonk, Madelon, Del Papa, Nicoletta, Bečvář, Radim, Guillén-Del-Castillo, Alfredo, Campochiaro, Corrado, Poormoghim, Hadi, Liem, Sophie, Lazzaroni, Maria-Grazia, Giollo, Alessandro, Mekinian, Arsène, de Vries-Bouwstra, Jeska, De Santis, Maria, Balbir-Gurman, Alexandra, Mihai, Carina, De Luca, Giacomo, Moiseev, Sergey, Zanatta, Elisabetta, Foti, Rosario, Rednic, Simona, Denton, Christopher, Cutolo, Maurizio, Belloli, Laura, Airo, Paolo, Garzanova, Liudmila, Moroncini, Gianluca, İnanç, Murat, Panopoulos, Stylianos, Tandaipan, Jose-Luis, Chatelus, Emmanuel, Rosato, Edoardo, Kuwana, Masataka, Yavuz, Sule, Alegre-Sancho, Juan J, Smith, Vanessa, Szűcs, Gabriella, Henes, Joerg, Rodríguez-Pintó, Ignasi, Atzeni, Fabiola, Spierings, Julia, Truchetet, Marie-Elise, Milchert, Marcin, Brito de Araujo, Daniel, Riemekasten, Gabriela, Bernardino, Vera, Martin, Thierry, Del Galdo, Francesco, Vacca, Alessandra, Mendoza, Fabian, Midtvedt, Øyvind, Murdaca, Giuseppe, Santiago, Tânia, Codullo, Veronica, Cacciapaglia, Fabio, Walker, Ulrich, Brunborg, Cathrine, Tirelli, Francesca, Allanore, Yannick, Furst, Daniel E, Matucci, Marco, Gabrielli, Armando, Distler, Oliver, and Hoffmann-Vold, Anna-Maria

Published
2024

7. Does the impact of COVID‐19 on patients with systemic sclerosis change over time?

Author

Deibel, Elisabeth, primary, Carreira, Patricia E., additional, Vonk, Madelon, additional, del Papa, Nicoletta, additional, Bečvář, Radim, additional, Guillén‐Del‐Castillo, Alfredo, additional, Campochiaro, Corrado, additional, Poormoghim, Hadi, additional, Liem, Sophie, additional, Lazzaroni, Maria‐Grazia, additional, Giollo, Alessandro, additional, Mekinian, Arsène, additional, de Vries‐Bouwstra, Jeska, additional, De Santis, Maria, additional, Balbir‐Gurman, Alexandra, additional, Mihai, Carina, additional, De Luca, Giacomo, additional, Moiseev, Sergey, additional, Zanatta, Elisabetta, additional, Foti, Rosario, additional, Rednic, Simona, additional, Denton, Christopher, additional, Cutolo, Maurizio, additional, Belloli, Laura, additional, Airo, Paolo, additional, Garzanova, Liudmila, additional, Moroncini, Gianluca, additional, İnanç, Murat, additional, Panopoulos, Stylianos, additional, Tandaipan, Jose‐Luis, additional, Chatelus, Emmanuel, additional, Rosato, Edoardo, additional, Kuwana, Masataka, additional, Yavuz, Sule, additional, Alegre‐Sancho, Juan J, additional, Smith, Vanessa, additional, Szűcs, Gabriella, additional, Henes, Joerg, additional, Rodríguez‐Pintó, Ignasi, additional, Atzeni, Fabiola, additional, Spierings, Julia, additional, Truchetet, Marie‐Elise, additional, Milchert, Marcin, additional, Brito de Araujo, Daniel, additional, Riemekasten, Gabriela, additional, Bernardino, Vera, additional, Martin, Thierry, additional, del Galdo, Francesco, additional, Vacca, Alessandra, additional, Mendoza, Fabian, additional, Midtvedt, Øyvind, additional, Murdaca, Giuseppe, additional, Santiago, Tânia, additional, Codullo, Veronica, additional, Cacciapaglia, Fabio, additional, Walker, Ulrich, additional, Brunborg, Cathrine, additional, Tirelli, Francesca, additional, Allanore, Yannick, additional, Furst, Daniel E., additional, Matucci, Marco, additional, Gabrielli, Armando, additional, Distler, Oliver, additional, and Hoffmann‐Vold, Anna‐Maria, additional

Published
2023
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8. Late Skin Fibrosis in Systemic Sclerosis: A Study from the EUSTAR Cohort

Author

Hughes, Michael; https://orcid.org/0000-0003-3361-4909, Huang, Suiyuan, Alegre-Sancho, Juan Jose, Carreira, Patricia E, Engelhart, Merete, Hachulla, Eric; https://orcid.org/0000-0001-7432-847X, Henes, Joerg, Kerzberg, Eduardo, Pozzi, Maria Rosa, Riemekasten, Gabriela, Smith, Vanessa; https://orcid.org/0000-0001-6271-7945, Szücs, Gabriella, Vanthuyne, Marie, Zanatta, Elisabetta, Distler, Oliver; https://orcid.org/0000-0002-0546-8310, Gabrielli, Armando G, Hoffmann-Vold, Anna-Maria; https://orcid.org/0000-0001-6467-7422, Steen, Virginia D, Khanna, Dinesh; https://orcid.org/0000-0003-1412-4453, Hughes, Michael; https://orcid.org/0000-0003-3361-4909, Huang, Suiyuan, Alegre-Sancho, Juan Jose, Carreira, Patricia E, Engelhart, Merete, Hachulla, Eric; https://orcid.org/0000-0001-7432-847X, Henes, Joerg, Kerzberg, Eduardo, Pozzi, Maria Rosa, Riemekasten, Gabriela, Smith, Vanessa; https://orcid.org/0000-0001-6271-7945, Szücs, Gabriella, Vanthuyne, Marie, Zanatta, Elisabetta, Distler, Oliver; https://orcid.org/0000-0002-0546-8310, Gabrielli, Armando G, Hoffmann-Vold, Anna-Maria; https://orcid.org/0000-0001-6467-7422, Steen, Virginia D, and Khanna, Dinesh; https://orcid.org/0000-0003-1412-4453

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 1st 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 1,043) 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 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
2023

9. Glucocorticoids prescribing practices in systemic sclerosis: an analysis of the EUSTAR database.

Author

Iudici, Michele, Mongin, Denis, Siegert, Elise, Carreira, Patricia E, Distler, Jörg, Henes, Jörg, Zanatta, Elisabetta, Hachulla, Eric, Luca, Giacomo De, Müller, Carolina de Souza, Santiago, Tânia, Tandaipan, José-Luis, Bianchi, Breno Valdetaro, Santis, Maria De, Hoffmann-Vold, Anna-Maria, Gabrielli, Armando, Distler, Oliver, Courvoisier, Delphine Sophie, and collaborators, EUSTAR

Subjects
THERAPEUTIC use of glucocorticoids, MULTIVARIATE analysis, SYSTEMIC scleroderma, REGRESSION analysis, TREATMENT effectiveness, DRUG prescribing, DISEASE prevalence, DESCRIPTIVE statistics, PHYSICIAN practice patterns
Abstract

Objectives To estimate the prevalence of long-term exposure to glucocorticoids (GCs) and to identify factors associated with, and variations in prescribing practices over time and across recruiting countries. Methods We included patients with SSc having a visit recorded in the EUSTAR database from January 2013 onward. We analysed the prevalence and the main features of GCs users, their exposure to GCs over time, and their GCs dosages. Multivariable linear regression was used to analyse the factors identified as associated with GCs intake duration. Time trends, and variations in GCs utilization across recruiting countries were explored. Missing data were imputed using multiple imputation with chained equations. Results The 9819 patients included were mostly females (85%), the majority had lcSSc (73%), and the median age was 58 years. At baseline, 34% of patients (n  = 2769/8109) (48% dcSSc vs 29% lcSSc) were on GCs, and the median dose was 7.5 mg/day. GCs users were more frequently males and anti-Scl70 positive, and more commonly had dcSSc and more severe disease. On average, GCs users spent 25% of their follow-up time (median 33.2 months) on GCs, with no significant between-subsets difference. Notably, 33% (n  = 971/2959) and 22% (n  = 647/2959) of patients followed up for >1 year had received GCs for >6 and >12 months, respectively. Multivariable analysis showed that patient and disease characteristics poorly explained the variability in GCs exposure (adjusted- R 2 = 0.06, P  < 0.001). GCs utilization varied within and across countries, and gradually decreased over time (36% in 2013 vs 23% in 2018). Conclusions GCs are widely and long-term prescribed in SSc, with significant between-countries and within-country differences. A gradual decrease in their utilization has been observed. [ABSTRACT FROM AUTHOR]

Published
2023
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10. Late skin fibrosis in systemic sclerosis: a study from the EUSTAR cohort.

Author

Hughes, Michael, Huang, Suiyuan, Alegre-Sancho, Juan Jose, Carreira, Patricia E, Engelhart, Merete, Hachulla, Eric, Henes, Joerg, Kerzberg, Eduardo, Pozzi, Maria Rosa, Riemekasten, Gabriela, Smith, Vanessa, Szücs, Gabriella, Vanthuyne, Marie, Zanatta, Elisabetta, Distler, Oliver, Gabrielli, Armando G, Hoffmann-Vold, Anna-Maria, Steen, Virginia D, Khanna, Dinesh, and Collaborators, EUSTAR

Subjects
SKIN diseases, DISEASE progression, SKIN, FIBROSIS, SYSTEMIC scleroderma, CONCEPTUAL structures, LONGITUDINAL method, DISEASE complications
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. [ABSTRACT FROM AUTHOR]

Published
2023
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11. Estimated glomerular filtration rate is a marker of mortality in the European Scleroderma Trials and Research Group (EUSTAR) database

Author

Gigante, Antonietta, Hoffmann-Vold, Anna-Maria, Fegatelli, Danilo Alunni, Gabrielli, Armando, Leodori, Giorgia, Coleiro, Bernard, De Santis, Maria, Dagna, Lorenzo, Alegre-Sancho, Juan Jose, Montecucco, Carlomaurizio, Carreira, Patricia E, Balbir-Gurman, Alexandra, Doria, Andrea, Riemekasten, Gabriela, Airò, Paolo, Distler, Jörg H W, Distler, Oliver, Rosato, Edoardo, EUSTAR collaborators, and University of Zurich

Subjects
Adult, Male, 0301 basic medicine, systemic sclerosis, Scleroderma Renal Crisis, Renal function, 610 Medicine & health, computer.software_genre, Scleroderma, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Rheumatology, Predictive Value of Tests, Risk Factors, medicine, Humans, Pharmacology (medical), In patient, Risk factor, 030203 arthritis & rheumatology, EUSTAR, Creatinine, Scleroderma, Systemic, Database, Proportional hazards model, business.industry, Incidence, 10051 Rheumatology Clinic and Institute of Physical Medicine, glomerular filtration rate, scleroderma renal crisis, Middle Aged, medicine.disease, Pulmonary hypertension, Survival Rate, 030104 developmental biology, chemistry, Female, business, computer, Glomerular Filtration Rate
Abstract

Objectives The study aim was to evaluate the estimated glomerular filtration rate (eGFR), its association with clinical disease and its predictive ability with respect to mortality in SSc patients from the European Scleroderma Trials and Research Group (EUSTAR) database. Methods SSc patients from the EUSTAR database who had items required for the calculation of eGFR at a baseline visit and a second follow-up visit available were included. A cut-off eGFR value of 60 ml/min was chosen for all SSc patients, and 30 ml/min for those with scleroderma renal crisis (SRC). Cox regression and competing risk analysis were performed to evaluate the use of eGFR as a predictive factor of mortality. Results A total of 3650 SSc patients were included in this study. The median serum level of creatinine and the mean of eGFR were 0.8 mg/dl (interquartile range = 0.6–0.9) and 86.6 ± 23.7 ml/min, respectively. The eGFR was significantly lower in patients with pulmonary hypertension. Overall survival (OS) was significantly reduced in SSc patients with eGFR 30 ml/min and those with eGFR Conclusion eGFR represents a predictive risk factor for overall survival in SSc. The eGFR, however, does not represent a risk factor for death in SRC.

Published
2021

12. Value of systolic pulmonary arterial pressure as a prognostic factor of death in the systemic sclerosis EUSTAR population

Author

Hachulla, Eric, Clerson, Pierre, Airò, Paolo, Cuomo, Giovanna, Allanore, Yannick, Caramaschi, Paola, Rosato, Edoardo, Carreira, Patricia E., Riccieri, Valeria, Sarraco, Marta, Denton, Christopher P., Riemekasten, Gabriela, Pozzi, Maria Rosa, Zeni, Silvana, Mihai, Carmen Marina, Ullman, Susanne, Distler, Oliver, Rednic, Simona, Smith, Vanessa, Walker, Ulrich A., Matucci-Cerinic, Marco, Müller-Ladner, Ulf, and Launay, David

Published
2015
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15. Additional file 2 of TBP and SNAP50 transcription factors bind specifically to the Pr77 promoter sequence from trypanosomatid non-LTR retrotransposons

Author

Mac��as, Francisco, Afonso-Lehmann, Raquel, Carreira, Patricia E., and Thomas, M. Carmen

Abstract

Additional file 2: Figure S2. Determination of the preferential binding site/s of rTBP and nuclear proteins to the Pr77 sequence. a Binding kinetics of rTBP to dsPr77 and double-stranded oligo pairs mapping the Pr77 sequence by EMSA. A 0.33 nM concentration of 32P-dsPr77 or each 32P-labelled oligo-pair was preincubated with increasing concentrations (0.63, 3.17, 6.35 ��M) of rTBP at 37 ��C for 30 min. Control reactions were performed without protein. Reactions were loaded on 6% native polyacrylamide gels, and quantification was carried out in a PhosphorImager. b Binding specificity of TBP to the Pr77 sequence by EMSA competition. EMSA was carried out after preincubation of 0.125 nM 32P-dsPr77 with 1.58 ��M rTBP and with different concentrations (as indicated, fold excess ranging from 5 to 500 times) of each cold oligo pair as DNA competitors. Control reactions were performed in a and b without protein. Reactions were loaded on 6% native polyacrylamide gels, and the results were visualized in a PhosphorImager. Shifted bands are indicated with black arrowheads, and the radiolabelled free form of each probe is indicated with an asterisk.

Published
2021
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16. Additional file 1 of TBP and SNAP50 transcription factors bind specifically to the Pr77 promoter sequence from trypanosomatid non-LTR retrotransposons

Author

Mac��as, Francisco, Afonso-Lehmann, Raquel, Carreira, Patricia E., and Thomas, M. Carmen

Abstract

Additional file 1: Figure S1. Binding kinetics of rTBP to the dsPr77 sequence by EMSA. A 0.33 nM concentration of 32P-labelled dsPr77 was preincubated with increasing concentrations (0.32���6.35 ��M) of rTBP at 37 ��C for 30 min. Control reactions were performed without protein. Reactions were loaded on 6% native polyacrylamide gels, and quantification was carried out in a PhosphorImager. The results were obtained from three independent experiments, as shown in Fig. 4a (top panel). The average values corresponding to the bound dsDNA fraction were plotted against the protein concentration, as shown in Fig. 4a (bottom panel). The curve corresponds to the best fit of the Hill equation to the experimental data [R2 (coefficient of determination) = 0.97]. The equation used was as follows: $$y = \frac{{B_{\max } \cdot x^{{\alpha_{{\text{H}}} }} }}{{K_{{\text{d}}}^{{\alpha_{{\text{H}}} }} + x^{{\alpha_{{\text{H}}} }} }}$$ y = B max �� x �� H K d �� H + x �� H , where ���x��� is the protein concentration and ���y��� is the radiolabelled dsDNA-bound fraction. Kd, defined as the protein concentration at which 50% of the dsDNA is bound, is indicated.

Published
2021
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17. The burden of systemic sclerosis in Switzerland - the Swiss systemic sclerosis EUSTAR cohort

Author

Hernández, Jasmin, Jordan, Suzana; https://orcid.org/0000-0002-8114-8239, Dobrota, Rucsandra; https://orcid.org/0000-0001-9819-7574, Iudici, Michele, Hasler, Paul, Ribi, Camillo, Villiger, Peter, Vlachoyiannopoulos, Panayiotis, Vacca, Alessandra, Garzanova, Ludmila, Giollo, Alessandro, Rosato, Edoardo; https://orcid.org/0000-0002-7417-8093, Kötter, Ina, Carreira, Patricia E, Doria, Andrea, Henes, Jörg, Müller-Ladner, Ulf, Smith, Vanessa; https://orcid.org/0000-0001-6271-7945, Distler, Jörg H W; https://orcid.org/0000-0001-7408-9333, Gabrielli, Armando, Hoffman-Vold, Anna-Maria, Walker, Ulrich A; https://orcid.org/0000-0002-9183-550X, Distler, Oliver; https://orcid.org/0000-0002-0546-8310, The Eustar Collaborators, Hernández, Jasmin, Jordan, Suzana; https://orcid.org/0000-0002-8114-8239, Dobrota, Rucsandra; https://orcid.org/0000-0001-9819-7574, Iudici, Michele, Hasler, Paul, Ribi, Camillo, Villiger, Peter, Vlachoyiannopoulos, Panayiotis, Vacca, Alessandra, Garzanova, Ludmila, Giollo, Alessandro, Rosato, Edoardo; https://orcid.org/0000-0002-7417-8093, Kötter, Ina, Carreira, Patricia E, Doria, Andrea, Henes, Jörg, Müller-Ladner, Ulf, Smith, Vanessa; https://orcid.org/0000-0001-6271-7945, Distler, Jörg H W; https://orcid.org/0000-0001-7408-9333, Gabrielli, Armando, Hoffman-Vold, Anna-Maria, Walker, Ulrich A; https://orcid.org/0000-0002-9183-550X, Distler, Oliver; https://orcid.org/0000-0002-0546-8310, and The Eustar Collaborators

Abstract

OBJECTIVES: Characteristics of Swiss patients with systemic sclerosis have not been described so far. The aim of the current study was to identify unmet needs in comparison with other European countries that could inform specific interventions to improve the care of systemic sclerosis patients. METHODS: We analysed Swiss and other European systemic sclerosis patients registered in European Scleroderma Trials And Research (EUSTAR) and the Very Early Diagnosis Of Systemic Sclerosis (VEDOSS) cohort. Demographics, clinical profiles, organ involvement and survival of established, early/mild and very early / very mild systemic sclerosis patients were described and compared between the cohorts. RESULTS: We included 679 Swiss and 8793 European systemic sclerosis patients in the analysis. Over 95% of patients in both cohorts were Caucasian, disease subsets were similar, and no age difference was found. The Swiss cohort had more male patients (25% vs 16% European, p = 0.005) and higher prevalence of early/mild and very early / very mild patients (26.1 vs 8.5% European and 14.9% vs 6.7% European, respectively, both p <0.0001). Disease duration in established systemic sclerosis patients at first presentation was numerically shorter but not significant in the Swiss cohort: 5.0 years (1–12) Swiss vs 6.0 years (2–12) years European, p = 0.055). Despite the earlier referral of Swiss patients to systemic sclerosis expert centres, they showed evidence of more severe disease, particularly in the limited cutaneous systemic sclerosis subset, but no differences in overall survival on longitudinal follow-up were observed. CONCLUSION: This is the first report of the national Swiss EUSTAR cohort. It identifies earlier referral to systemic sclerosis expert centres, before major organ damage occurs, and when outcome can still be modified, as a priority to improve care of patients with systemic sclerosis.

Published
2021

20. 2013 Classification Criteria for Systemic Sclerosis: An American College of Rheumatology/European League Against Rheumatism Collaborative Initiative

Author

van den Hoogen, Frank, Khanna, Dinesh, Fransen, Jaap, Johnson, Sindhu R., Baron, Murray, Tyndall, Alan, Matucci-Cerinic, Marco, Naden, Raymond P., Medsger, Thomas A., Jr., Carreira, Patricia E., Riemekasten, Gabriela, Clements, Philip J., Denton, Christopher P., Distler, Oliver, Allanore, Yannick, Furst, Daniel E., Gabrielli, Armando, Mayes, Maureen D., van Laar, Jacob M., Seibold, James R., Czirjak, Laszlo, Steen, Virginia D., Inanc, Murat, Kowal-Bielecka, Otylia, Müller-Ladner, Ulf, Valentini, Gabriele, Veale, Douglas J., Vonk, Madelon C., Walker, Ulrich A., Chung, Lorinda, Collier, David H., Csuka, Mary Ellen, Fessler, Barri J., Guiducci, Serena, Herrick, Ariane, Hsu, Vivien M., Jimenez, Sergio, Kahaleh, Bashar, Merkel, Peter A., Sierakowski, Stanislav, Silver, Richard M., Simms, Robert W., Varga, John, and Pope, Janet E.

Published
2013
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21. Association of a rare variant of the TNFSF13B gene with susceptibility to Rheumatoid Arthritis and Systemic Lupus Erythematosus

Author

Junta de Andalucía, Redes Temáticas de Investigación Cooperativa en Salud (España), Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Carreira, Patricia E. [0000-0001-8279-3806], González-Serna, David, Ortiz-Fernández, Lourdes, Vargas, Sofía, García, Antonio, Raya, Enrique, Fernández-Gutiérrez, Benjamín, López-Longo, Francisco Javier, Balsa, Alejandro, González-Álvaro, Isidoro, Narváez, Javier, Gómez-Vaquero, C., Sabio, José Mario, García-Portales, Rosa, González-Escribano, María Francisca, Tolosa-Vilella, Carles, Carreira, Patricia E., Kiemeney, Lambertus A., Coenen, Marieke J. H., Witte, Torsten, Schneider, Matthias, González-Gay, M. A., Martín, Javier, Junta de Andalucía, Redes Temáticas de Investigación Cooperativa en Salud (España), Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Carreira, Patricia E. [0000-0001-8279-3806], González-Serna, David, Ortiz-Fernández, Lourdes, Vargas, Sofía, García, Antonio, Raya, Enrique, Fernández-Gutiérrez, Benjamín, López-Longo, Francisco Javier, Balsa, Alejandro, González-Álvaro, Isidoro, Narváez, Javier, Gómez-Vaquero, C., Sabio, José Mario, García-Portales, Rosa, González-Escribano, María Francisca, Tolosa-Vilella, Carles, Carreira, Patricia E., Kiemeney, Lambertus A., Coenen, Marieke J. H., Witte, Torsten, Schneider, Matthias, González-Gay, M. A., and Martín, Javier

Abstract

A rare variant (BAFF-var) of the tumor necrosis factor superfamily 13b (TNFSF13B) gene has been recently associated with multiple sclerosis (MS) and systemic lupus erythematosus (SLE). The aim of this study was to investigate the association between TNFSF13B BAFF-var and susceptibility to rheumatoid arthritis (RA) and replicate that association in SLE. 6,218 RA patients, 2,575 SLE patients and 4,403 healthy controls from three different countries were included in the study. TNFSF13B BAFF-var was genotyped using TaqMan allelic discrimination assay. PLINK software was used for statistical analyses. TNFSF13B BAFF-var was significantly associated with RA (p = 0.015, OR = 1.21, 95% CI = 1.03–1.41) in the Spanish cohort. A trend of association was observed in the Dutch (p = 0.115) and German (p = 0.228) RA cohorts. A meta-analysis of the three RA cohorts included in this study revealed a statistically significant association (p = 0.002, OR = 1.24, 95% CI = 1.10–1.38). In addition, TNFSF13B BAFF-var was significantly associated with SLE in the Spanish (p = 0.001, OR = 1.41, 95% CI = 1.14–1.74) and the German cohorts (p = 0.030, OR = 1.86, 95% CI = 1.05–3.28), with a statistically significant p-value obtained in the meta-analysis (p = 0.0002, OR = 1.46, 95% CI = 1.09–2.32). The results obtained confirm the known association of TNFSF13B BAFF-var with SLE and, for the first time, demonstrate that this variant contributes to susceptibility to RA.

Published
2018

22. Smoking in Systemic Sclerosis: a Longitudinal European Scleroderma Trials and Research Group Study

Author

Jaeger, Veronika K, Valentini, Gabriele, Hachulla, Eric, Cozzi, Franco, Distler, Oliver, Airó, Paolo, Czirják, Laszlo, Allanore, Yannick, Siegert, Elise, Rosato, Edoardo, Matucci-Cerinic, Marco, Caimmi, Cristian, Henes, Jörg, Carreira, Patricia E, Smith, Vanessa, Del Galdo, Francesco, Denton, Christopher P, Ullman, Susanne, Langhe, Ellen De, Riccieri, Valeria, Alegre-Sancho, Juan J, Rednic, Simona, Müller-Ladner, Ulf, Walker, Ulrich A, Jaeger, Veronika K, Valentini, Gabriele, Hachulla, Eric, Cozzi, Franco, Distler, Oliver, Airó, Paolo, Czirják, Laszlo, Allanore, Yannick, Siegert, Elise, Rosato, Edoardo, Matucci-Cerinic, Marco, Caimmi, Cristian, Henes, Jörg, Carreira, Patricia E, Smith, Vanessa, Del Galdo, Francesco, Denton, Christopher P, Ullman, Susanne, Langhe, Ellen De, Riccieri, Valeria, Alegre-Sancho, Juan J, Rednic, Simona, Müller-Ladner, Ulf, and Walker, Ulrich A

Subjects
Systemic sclerosi, prevalence, organ manifestation, progression, smoking, respiratory tract diseases
Abstract

OBJECTIVE: Data on the role of tobacco exposure in systemic sclerosis (SSc; scleroderma) severity and progression are scarce. We aimed to assess the effects of smoking on the evolution of pulmonary and skin manifestations, based on the European Scleroderma Trials and Research group database. METHODS: Adult SSc patients with data on smoking history and a 12-24-month follow-up visit were included. Associations of severity and progression of organ involvement with smoking history and the Comprehensive Smoking Index were assessed using multivariable regression analyses. RESULTS: A total of 3,319 patients were included (mean age 57 years, 85% female); 66% were never smokers, 23% were ex-smokers, and 11% were current smokers. Current smokers had a lower percentage of antitopoisomerase autoantibodies than previous or never smokers (31% versus 40% and 45%, respectively). Never smokers had a higher baseline forced expiratory volume in 1 second/forced vital capacity (FEV1 /FVC) ratio than previous and current smokers (P < 0.001). The FEV1 /FVC ratio declined faster in current smokers than in never smokers (P = 0.05) or ex-smokers (P = 0.01). The baseline modified Rodnan skin thickness score (MRSS) and the MRSS decline were comparable across smoking groups. Although heavy smoking (>25 pack-years) increased the odds of digital ulcers by almost 50%, there was no robust adverse association of smoking with digital ulcer development. CONCLUSION: The known adverse effect of smoking on bronchial airways and alveoli is also observed in SSc patients; however, robust adverse effects of smoking on the progression of SSc-specific pulmonary or cutaneous manifestations were not observed. ispartof: Arthritis and Rheumatology vol:70 issue:11 pages:1829-1834 ispartof: location:United States status: published

Published
2018

23. Additional file 1 of Health Assessment Questionnaire-Disability Index (HAQ-DI) use in modelling disease progression in diffuse cutaneous systemic sclerosis: an analysis from the EUSTAR database

Author

Allanore, Yannick, Bozzi, Sylvie, Terlinden, Augustin, Doerte Huscher, Amand, Caroline, Soubrane, Christina, Siegert, Elise, Czirják, László, Carreira, Patricia E., Hachulla, Eric, Zanatta, Elisabetta, Mengtao Li, Airò, Paolo, Mendoza, Fabian A., Rosato, Edoardo, and Distler, Oliver

Subjects
musculoskeletal diseases
Abstract

Additional file 1: Fig. S1. Immunomodulator treatment received at baseline according to HAQ-DI score assessments. Table S1. Results of the multistate model calibration on longitudinal patient-level data (transition intensities between the HAQ-DI states in function of covariates). Table S2. Results of a survival model calibration on longitudinal patient-level data (transition intensities between the organ states in function of covariates). Table S3. Univariate and multivariable Cox regression analysis of the HAQ-DI domains influencing mortality risk in patients with ≥ 1 HAQ-DI measurement.

Published
2020
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24. Health Assessment Questionnaire-Disability Index (HAQ-DI) use in modelling disease progression in diffuse cutaneous systemic sclerosis: an analysis from the EUSTAR database.

Author

Allanore, Yannick, Bozzi, Sylvie, Terlinden, Augustin, Huscher, Doerte, Amand, Caroline, Soubrane, Christina, Siegert, Elise, Czirják, László, Carreira, Patricia E, Hachulla, Eric, Zanatta, Elisabetta, Li, Mengtao, Airò, Paolo, Mendoza, Fabian A, Rosato, Edoardo, Distler, Oliver, Allanore, Yannick, Bozzi, Sylvie, Terlinden, Augustin, Huscher, Doerte, Amand, Caroline, Soubrane, Christina, Siegert, Elise, Czirják, László, Carreira, Patricia E, Hachulla, Eric, Zanatta, Elisabetta, Li, Mengtao, Airò, Paolo, Mendoza, Fabian A, Rosato, Edoardo, and Distler, Oliver

Abstract

BACKGROUND: Patients with diffuse cutaneous systemic sclerosis (dcSSc) have a poor prognosis. The importance of monitoring subjective measures of functioning and disability, such as the Health Assessment Questionnaire-Disability Index (HAQ-DI), is important as dcSSc is rated by patients as worse than diabetes or hemodialysis for quality of life impairment. This European Scleroderma Trials and Research (EUSTAR) database analysis was undertaken to examine the importance of impaired functionality in dcSSc prognosis. The primary objectives were to identify predictors of death and HAQ-DI score progression over 1 year. HAQ-DI score, major advanced organ involvement, and death rate were also used to develop a comprehensive model to predict lifetime dcSSc progression. METHODS: This was an observational, longitudinal study in patients with dcSSc registered in EUSTAR. Death and HAQ-DI scores were, respectively, analyzed by Cox regression and linear regression analyses in relation to baseline covariates. A microsimulation Markov model was developed to estimate/predict natural progression of dcSSc over a patient's lifetime. RESULTS: The analysis included dcSSc patients with (N = 690) and without (N = 4132) HAQ-DI score assessments from the EUSTAR database. Baseline HAQ-DI score, corticosteroid treatment, and major advanced organ involvement were predictive of death on multivariable analysis; a 1-point increase in baseline HAQ-DI score multiplied the risk of death by 2.7 (p < 0.001) and multiple advanced major organ involvement multiplied the risk of death by 2.8 (p < 0.05). Multivariable analysis showed that baseline modified Rodnan Skin Score (mRSS) and baseline HAQ-DI score were associated with HAQ-DI score progression at 1 year (p < 0.05), but there was no association between baseline organ involvement and HAQ-DI score progression at 1 year. HAQ-DI score, major advanced organ involvement, and death were successfully used to model long-term disease progression in dcSSc. CO

Published
2020

25. Health Assessment Questionnaire-Disability Index (HAQ-DI) use in modelling disease progression in diffuse cutaneous systemic sclerosis: an analysis from the EUSTAR database

Author

Allanore, Yannick; https://orcid.org/0000-0002-6149-0002, Bozzi, Sylvie, Terlinden, Augustin, Huscher, Doerte, Amand, Caroline, Soubrane, Christina, Siegert, Elise; https://orcid.org/0000-0002-9594-0446, Czirják, László, Carreira, Patricia E, Hachulla, Eric; https://orcid.org/0000-0001-7432-847X, Zanatta, Elisabetta, Li, Mengtao; https://orcid.org/0000-0003-4252-2889, Airò, Paolo, Mendoza, Fabian A, Rosato, Edoardo; https://orcid.org/0000-0002-7417-8093, Distler, Oliver; https://orcid.org/0000-0002-0546-8310, EUSTAR Collaborators, Allanore, Yannick; https://orcid.org/0000-0002-6149-0002, Bozzi, Sylvie, Terlinden, Augustin, Huscher, Doerte, Amand, Caroline, Soubrane, Christina, Siegert, Elise; https://orcid.org/0000-0002-9594-0446, Czirják, László, Carreira, Patricia E, Hachulla, Eric; https://orcid.org/0000-0001-7432-847X, Zanatta, Elisabetta, Li, Mengtao; https://orcid.org/0000-0003-4252-2889, Airò, Paolo, Mendoza, Fabian A, Rosato, Edoardo; https://orcid.org/0000-0002-7417-8093, Distler, Oliver; https://orcid.org/0000-0002-0546-8310, and EUSTAR Collaborators

Abstract

BACKGROUND: Patients with diffuse cutaneous systemic sclerosis (dcSSc) have a poor prognosis. The importance of monitoring subjective measures of functioning and disability, such as the Health Assessment Questionnaire-Disability Index (HAQ-DI), is important as dcSSc is rated by patients as worse than diabetes or hemodialysis for quality of life impairment. This European Scleroderma Trials and Research (EUSTAR) database analysis was undertaken to examine the importance of impaired functionality in dcSSc prognosis. The primary objectives were to identify predictors of death and HAQ-DI score progression over 1 year. HAQ-DI score, major advanced organ involvement, and death rate were also used to develop a comprehensive model to predict lifetime dcSSc progression. METHODS: This was an observational, longitudinal study in patients with dcSSc registered in EUSTAR. Death and HAQ-DI scores were, respectively, analyzed by Cox regression and linear regression analyses in relation to baseline covariates. A microsimulation Markov model was developed to estimate/predict natural progression of dcSSc over a patient's lifetime. RESULTS: The analysis included dcSSc patients with (N = 690) and without (N = 4132) HAQ-DI score assessments from the EUSTAR database. Baseline HAQ-DI score, corticosteroid treatment, and major advanced organ involvement were predictive of death on multivariable analysis; a 1-point increase in baseline HAQ-DI score multiplied the risk of death by 2.7 (p < 0.001) and multiple advanced major organ involvement multiplied the risk of death by 2.8 (p < 0.05). Multivariable analysis showed that baseline modified Rodnan Skin Score (mRSS) and baseline HAQ-DI score were associated with HAQ-DI score progression at 1 year (p < 0.05), but there was no association between baseline organ involvement and HAQ-DI score progression at 1 year. HAQ-DI score, major advanced organ involvement, and death were successfully used to model long-term disease progression in dcSSc. CO

Published
2020

27. Estimated glomerular filtration rate is a marker of mortality in the European Scleroderma Trials and Research Group (EUSTAR) database.

Author

Gigante, Antonietta, Hoffmann-Vold, Anna-Maria, Fegatelli, Danilo Alunni, Gabrielli, Armando, Leodori, Giorgia, Coleiro, Bernard, Santis, Maria De, Dagna, Lorenzo, Alegre-Sancho, Juan Jose, Montecucco, Carlomaurizio, Carreira, Patricia E, Balbir-Gurman, Alexandra, Doria, Andrea, Riemekasten, Gabriela, Airò, Paolo, Distler, Jörg, Distler, Oliver, Rosato, Edoardo, and collaborators, the EUSTAR

Subjects
GLOMERULAR filtration rate, PATIENT aftercare, BLOOD pressure, PREDICTIVE tests, CONFIDENCE intervals, PULMONARY hypertension, MULTIVARIATE analysis, SYSTEMIC scleroderma, PULMONARY artery, RISK assessment, SEX distribution, DESCRIPTIVE statistics, MEDICAL appointments, DEATH, PROPORTIONAL hazards models, CREATININE, DISEASE complications
Abstract

Objectives The study aim was to evaluate the estimated glomerular filtration rate (eGFR), its association with clinical disease and its predictive ability with respect to mortality in SSc patients from the European Scleroderma Trials and Research Group (EUSTAR) database. Methods SSc patients from the EUSTAR database who had items required for the calculation of eGFR at a baseline visit and a second follow-up visit available were included. A cut-off eGFR value of 60 ml/min was chosen for all SSc patients, and 30 ml/min for those with scleroderma renal crisis (SRC). Cox regression and competing risk analysis were performed to evaluate the use of eGFR as a predictive factor of mortality. Results A total of 3650 SSc patients were included in this study. The median serum level of creatinine and the mean of eGFR were 0.8 mg/dl (interquartile range = 0.6–0.9) and 86.6 ± 23.7 ml/min, respectively. The eGFR was significantly lower in patients with pulmonary hypertension. Overall survival (OS) was significantly reduced in SSc patients with eGFR < 60 ml/min compared with patients with eGFR ≥ 60 ml/min [OS at 5 years 0.763 (95% CI: 0.700, 0.814) vs 0.903 (95% CI: 0.883, 0.919; P  < 0.001)]. In multivariable analysis, OS was associated with male gender (P  < 0.01), systolic pulmonary arterial pressure (sPAP) (P  < 0.001) and eGFR (P  < 0.001). The cumulative incidence of deaths due to SSc was associated with increased sPAP (P  < 0.001) and reduced eGFR (P  < 0.05). The OS at 5 years of 53 SRC patients was not significantly different between SSc patients with eGFR > 30 ml/min and those with eGFR <30 ml/min. Conclusion eGFR represents a predictive risk factor for overall survival in SSc. The eGFR, however, does not represent a risk factor for death in SRC. [ABSTRACT FROM AUTHOR]

Published
2022
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28. 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

29. 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

30. 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

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

Author

Elhai, Muriel, Boubaya, Marouane, Distler, Oliver, Smith, Vanessa, Matucci-Cerinic, Marco, Alegre Sancho, Juan Jose, Truchetet, Marie-Elise, Braun-Moscovici, Yolanda, Iannone, Florenzo, Novikov, Pavel I., Lescoat, Alain, Siegert, Elise, Castellvi, Ivan, Airo, Paolo, Vettori, Serena, De Langhe, Ellen, Hachulla, Eric, Erler, Anne, Ananieva, Lidia, Krusche, Martin, Lopez-Longo, F. J., Distler, Joerg H. W., Hunzelmann, Nicolas, 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, Guiducci, Serena, Walker, Ulrich A., Kyburz, Diego, Lapadula, Giovanni, Maurer, Britta, Jordan, Suzana, Dobrota, Rucsandra, Becvar, Radim, Sierakowsky, Stanislaw, Bielecka, Otylia Kowal, Sulli, Alberto, Cutolo, Maurizio, Cuomo, Giovanna, Nicoara, Ileana, Kahan, Andre, Vlachoyiannopoulos, Panayiotis G., Montecucco, Carlo Maurizio, Caporali, Roberto, Stork, Jiri, Inanc, Murat, Carreira, Patricia E., Novak, Srdan, Czirjak, Laszlo, Varju, Cecilia, Kucharz, Eugene J., Kotulska, Anna, Kopec-Medrek, Magdalena, Widuchowska, Malgorzata, Cozzi, Franco, Rozman, Blaz, Mallia, Carmel, Coleiro, Bernard, Gabrielli, Armando, Farge, Dominique, Wu, Chen, Marjanovic, Zora, Faivre, Helene, Hij, Darin, Dhamadi, Roza, Wollheim, Frank, Scheja, Agneta, Wuttge, Dirk M., Andreasson, Kristofer, Martinovic, Duska, Balbir-Gurman, Alexandra, Trotta, F., Lo Monaco, Andrea, Pellerito, Raffaele, Mauriziano, Ospedale, Caramaschi, Paola, Morovic-Vergles, Jadranka, Black, Carol, Denton, Christopher, Damjanov, Nemanja, Henes, Jorg, Santamaria, Vera Ortiz, Heitmann, Stefan, Krasowska, Dorota, Hasler, Paul, Burkhardt, Harald, Himsel, Andrea, Bajocchi, Gianluigi, Da Silva, Jose Antonio Pereira, Salvador, Maria Joao, Stamenkovic, Bojana, Stankovic, Aleksandra, Selmi, Carlo Francesco, De Santis, Maria, Tikly, Mohammed, Denisov, Lev N., Herrick, Ariane, Mueller-Ladner, Ulf, Frerix, Marc, Tarner, Ingo, Scorza, Raffaella, Puppo, Francesco, Engelhart, Merete, Strauss, Gitte, Nielsen, Henrik, Damgaard, Kirsten, Szucs, Gabriela, Mendoza, Antonio Zea, de la Puente, Carlos, Giraldo, Sifuentes W. A., Midtvedt, Oyvind, Reiseter, Silje, Garen, Torhild, Launay, David, Valesini, Guido, Ionescu, Ruxandra Maria, Groseanu, Laura, Opris, Daniela, Cornateanu, Roxana Sfrent, Ionitescu, Razvan, Gherghe, Ana Maria, Soare, Alina, Gorga, Marilena, Bojinca, Mihai, Milicescu, Mihaela, Sunderkotter, Cord, Kuhn, Annegret, Sandorfi, Nora, Schett, Georg, Beyer, Christian, Meroni, Pierluigi, Ingegnoli, Francesca, Mouthon, Luc, De Keyser, Filip, Melsens, Karin, Cantatore, Francesco P., Corrado, Ada, Iversen, Line, von Muhlen, Carlos Alberto, Bohn, Jussara Marilu, Lonzetti, Lilian Scussel, Eyerich, Kilian, Hein, Rudiger, Knott, Elisabeth, Wiland, Piotr, Szmyrka-Kaczmarek, Magdalena, Sokolik, Renata, Morgiel, Ewa, Madej, Marta, Houssiau, Frederic A., Krummel-Lorenz, Brigitte, Saar, Petra, Aringer, Martin, Gunther, Claudia, Westhovens, Rene, Lenaerts, Jan, Anic, Branimir, Baresic, Marko, Mayer, Miroslav, Uprus, Maria, Otsa, Kati, Granel, Brigitte, Muller, Carolina de Souza, Radominski, Sebastiao C., Azevedo, Valderilio F., Jimenez, Sergio, Busquets, Joanna, Agachi, Svetlana, Groppa, Liliana, Chiaburu, Lealea, Russu, Eugen, Popa, Sergei, Zenone, Thierry, Pileckyte, Margarita, Mathieu, Alessandro, Vacca, Alessandra, Sampaio-Barros, Percival D., Yoshinari, Natalino H., Marangoni, Roberta G., Martin, Patricia, Fuocco, Luiza, Stebbings, Simon, Highton, John, Chapman, Peter, O'Donnell, John, Stamp, Lisa, Doube, Alan, Solanki, Kamal, Veale, Douglas, O'Rourke, Marie, Loyo, Esthela, Li, Mengtao, Mohamed, Walid Ahmed Abdel Atty, Amoroso, Antonio, Gigante, Antonietta, Oksel, Fahrettin, Yargucu, Figen, Tanaseanu, Cristina-Mihaela, Popescu, Monica, Dumitrascu, Alina, Tiglea, Isabela, Foti, Rosario, Chirieac, Rodica, Furst, Daniel, Villiger, Peter, Adler, Sabine, van Laar, Jacob, Kayser, Cristiane, Fathi, Nihal, Hassanien, Manal, Lefebvre, Paloma Garcia de la Pena, Rubio, Silvia Rodriguez, Exposito, Marta Valero, Chatelus, Emmanuel, Sibilia, Jean, Gottenberg, Jacques Eric, Chifflot, Helene, Litinsky, Ira, Emery, Paul, Buch, Maya, Del Galdo, Francesco, Venalis, Algirdas, Butrimiene, Irena, Venalis, Paulius, Rugiene, Rita, Karpec, Diana, Lasky, Joseph A., Cosentino, Vanesa, Kerzberg, Eduardo, Montoya, Fabiana, Bianchi, Washington, Carneiro, Sueli, Maretti, Giselle Baptista, Bianchi, Dante Valdetaro, Limonta, Massimiliano, Brucato, Antonio Luca, Lupi, Elide, Rosner, Itzhak, Rozenbaum, Michael, Slobodin, Gleb, Boulman, Nina, Rimar, Doron, Couto, Maura, Kahl, Sarah, Chen, Fei, McCloskey, Deborah, Malveaux, Halina, Spertini, Francois, Ribi, Camillo, Buss, Guillaume, Martin, Thierry, Guffroy, Aurelien, Poindron, Vincent, Chotchaeva, Fatima, Mukhin, Nikolay A., Moiseev, Sergey, Elhai, Muriel, Boubaya, Marouane, Distler, Oliver, Smith, Vanessa, Matucci-Cerinic, Marco, Alegre Sancho, Juan Jose, Truchetet, Marie-Elise, Braun-Moscovici, Yolanda, Iannone, Florenzo, Novikov, Pavel I., Lescoat, Alain, Siegert, Elise, Castellvi, Ivan, Airo, Paolo, Vettori, Serena, De Langhe, Ellen, Hachulla, Eric, Erler, Anne, Ananieva, Lidia, Krusche, Martin, Lopez-Longo, F. J., Distler, Joerg H. W., Hunzelmann, Nicolas, 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, Guiducci, Serena, Walker, Ulrich A., Kyburz, Diego, Lapadula, Giovanni, Maurer, Britta, Jordan, Suzana, Dobrota, Rucsandra, Becvar, Radim, Sierakowsky, Stanislaw, Bielecka, Otylia Kowal, Sulli, Alberto, Cutolo, Maurizio, Cuomo, Giovanna, Nicoara, Ileana, Kahan, Andre, Vlachoyiannopoulos, Panayiotis G., Montecucco, Carlo Maurizio, Caporali, Roberto, Stork, Jiri, Inanc, Murat, Carreira, Patricia E., Novak, Srdan, Czirjak, Laszlo, Varju, Cecilia, Kucharz, Eugene J., Kotulska, Anna, Kopec-Medrek, Magdalena, Widuchowska, Malgorzata, Cozzi, Franco, Rozman, Blaz, Mallia, Carmel, Coleiro, Bernard, Gabrielli, Armando, Farge, Dominique, Wu, Chen, Marjanovic, Zora, Faivre, Helene, Hij, Darin, Dhamadi, Roza, Wollheim, Frank, Scheja, Agneta, Wuttge, Dirk M., Andreasson, Kristofer, Martinovic, Duska, Balbir-Gurman, Alexandra, Trotta, F., Lo Monaco, Andrea, Pellerito, Raffaele, Mauriziano, Ospedale, Caramaschi, Paola, Morovic-Vergles, Jadranka, Black, Carol, Denton, Christopher, Damjanov, Nemanja, Henes, Jorg, Santamaria, Vera Ortiz, Heitmann, Stefan, Krasowska, Dorota, Hasler, Paul, Burkhardt, Harald, Himsel, Andrea, Bajocchi, Gianluigi, Da Silva, Jose Antonio Pereira, Salvador, Maria Joao, Stamenkovic, Bojana, Stankovic, Aleksandra, Selmi, Carlo Francesco, De Santis, Maria, Tikly, Mohammed, Denisov, Lev N., Herrick, Ariane, Mueller-Ladner, Ulf, Frerix, Marc, Tarner, Ingo, Scorza, Raffaella, Puppo, Francesco, Engelhart, Merete, Strauss, Gitte, Nielsen, Henrik, Damgaard, Kirsten, Szucs, Gabriela, Mendoza, Antonio Zea, de la Puente, Carlos, Giraldo, Sifuentes W. A., Midtvedt, Oyvind, Reiseter, Silje, Garen, Torhild, Launay, David, Valesini, Guido, Ionescu, Ruxandra Maria, Groseanu, Laura, Opris, Daniela, Cornateanu, Roxana Sfrent, Ionitescu, Razvan, Gherghe, Ana Maria, Soare, Alina, Gorga, Marilena, Bojinca, Mihai, Milicescu, Mihaela, Sunderkotter, Cord, Kuhn, Annegret, Sandorfi, Nora, Schett, Georg, Beyer, Christian, Meroni, Pierluigi, Ingegnoli, Francesca, Mouthon, Luc, De Keyser, Filip, Melsens, Karin, Cantatore, Francesco P., Corrado, Ada, Iversen, Line, von Muhlen, Carlos Alberto, Bohn, Jussara Marilu, Lonzetti, Lilian Scussel, Eyerich, Kilian, Hein, Rudiger, Knott, Elisabeth, Wiland, Piotr, Szmyrka-Kaczmarek, Magdalena, Sokolik, Renata, Morgiel, Ewa, Madej, Marta, Houssiau, Frederic A., Krummel-Lorenz, Brigitte, Saar, Petra, Aringer, Martin, Gunther, Claudia, Westhovens, Rene, Lenaerts, Jan, Anic, Branimir, Baresic, Marko, Mayer, Miroslav, Uprus, Maria, Otsa, Kati, Granel, Brigitte, Muller, Carolina de Souza, Radominski, Sebastiao C., Azevedo, Valderilio F., Jimenez, Sergio, Busquets, Joanna, Agachi, Svetlana, Groppa, Liliana, Chiaburu, Lealea, Russu, Eugen, Popa, Sergei, Zenone, Thierry, Pileckyte, Margarita, Mathieu, Alessandro, Vacca, Alessandra, Sampaio-Barros, Percival D., Yoshinari, Natalino H., Marangoni, Roberta G., Martin, Patricia, Fuocco, Luiza, Stebbings, Simon, Highton, John, Chapman, Peter, O'Donnell, John, Stamp, Lisa, Doube, Alan, Solanki, Kamal, Veale, Douglas, O'Rourke, Marie, Loyo, Esthela, Li, Mengtao, Mohamed, Walid Ahmed Abdel Atty, Amoroso, Antonio, Gigante, Antonietta, Oksel, Fahrettin, Yargucu, Figen, Tanaseanu, Cristina-Mihaela, Popescu, Monica, Dumitrascu, Alina, Tiglea, Isabela, Foti, Rosario, Chirieac, Rodica, Furst, Daniel, Villiger, Peter, Adler, Sabine, van Laar, Jacob, Kayser, Cristiane, Fathi, Nihal, Hassanien, Manal, Lefebvre, Paloma Garcia de la Pena, Rubio, Silvia Rodriguez, Exposito, Marta Valero, Chatelus, Emmanuel, Sibilia, Jean, Gottenberg, Jacques Eric, Chifflot, Helene, Litinsky, Ira, Emery, Paul, Buch, Maya, Del Galdo, Francesco, Venalis, Algirdas, Butrimiene, Irena, Venalis, Paulius, Rugiene, Rita, Karpec, Diana, Lasky, Joseph A., Cosentino, Vanesa, Kerzberg, Eduardo, Montoya, Fabiana, Bianchi, Washington, Carneiro, Sueli, Maretti, Giselle Baptista, Bianchi, Dante Valdetaro, Limonta, Massimiliano, Brucato, Antonio Luca, Lupi, Elide, Rosner, Itzhak, Rozenbaum, Michael, Slobodin, Gleb, Boulman, Nina, Rimar, Doron, Couto, Maura, Kahl, Sarah, Chen, Fei, McCloskey, Deborah, Malveaux, Halina, Spertini, Francois, Ribi, Camillo, Buss, Guillaume, Martin, Thierry, Guffroy, Aurelien, Poindron, Vincent, Chotchaeva, Fatima, Mukhin, Nikolay A., and Moiseev, Sergey

Abstract

Objective To assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice. Methods We 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. Results 254 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], p<0.0001). Patients treated concomitantly with mycophenolate mofetil had a trend for better outcomes as compared with patients receiving rituximab alone (delta FVC: 5.22 [0.83-9.62]; p=0.019 as compared with controls vs 3 [0.66-5.35]; p=0.012). Conclusion Rituximab 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

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

Author

Herrick, Ariane, Peytrignet, Sebastien, Lunt, Mark, Pan, Xiaoyan, Dinsdale, Graham, Brown, Edith, Czirják, László, Distler, Jörg H.W., Distler, Oliver, Fligelstone, Kim, Gregory, William J, Ochiel, Rachel, Vonk, Madelon C, Ancuta, Codrina, Ong, Voon H, Farge, Dominique, Hudson, Marie, Matucci-Cerinic, Marco, Balbir-Gurman, Alexandra, Midtvedt, Øyvind, Jobanputra, Paresh, Jordan, Alison C, Stevens, Wendy, Moinzadeh, Pia, Hall, Frances C, Agard, Christian, Anderson, Marina E, Diot, Elisabeth, Madhok, Rajan, Akil, Mohammed, Buch, Maya, Chung, Lorinda, Damjanov, Nemanja, Gunawardena, Harsha, Lanyon, Peter, Ahmad, Yasmeen, Chakravarty, Kuntal, Jacobsen, Soren, MacGregor, Alexander J, McHugh, Neil, Müller-Ladner, Ulf, Riemekasten, Gabriela, Becker, Michael, Roddy, Janet, Carreira, Patricia E, Hachulla, Eric, Hamilton, Jennifer, Inanç, Murat, McLaren, John S, van Laar, Jacob M., Pathare, Sanjay, Proudman, Susannah, Rudin, Anna, Sahhar, Joanne, Coppere, Brigitte, Serratrice, Christine, Sheeran, Tom, Veale, Douglas J, Grange, Claire, Trad, Georges-Selim, and Denton, Christopher P.

Published
2018

36. Brief Report: Smoking in Systemic Sclerosis: A Longitudinal European Scleroderma Trials and Research Group Study

Author

Jaeger, Veronika K, Valentini, Gabriele, Hachulla, Eric, Cozzi, Franco, Distler, Oliver, Airó, Paolo, Czirják, Laszlo, Allanore, Yannick, Siegert, Elise, Rosato, Edoardo, Matucci-Cerinic, Marco, Caimmi, Cristian, Henes, Jörg, Carreira, Patricia E, Smith, Vanessa, Del Galdo, Francesco, Denton, Christopher P, Ullman, Susanne, De Langhe, Ellen, Riccieri, Valeria, Alegre-Sancho, Juan J, Rednic, Simona, Müller-Ladner, Ulf, Walker, Ulrich A, EUSTAR co-authors, and Chizzolini, Carlo

Subjects
Male, Vital capacity, systemic sclerosis, Vital Capacity, Severity of Illness Index, Scleroderma, 0302 clinical medicine, Forced Expiratory Volume, Immunology and Allergy, DNA Topoisomerases/immunology, Longitudinal Studies, skin and connective tissue diseases, Lung, Skin, ddc:616, Smokers, integumentary system, Smoking, Middle Aged, Disease Progression, Female, Autoantibodies/immunology, Adult, medicine.medical_specialty, Skin/pathology, Immunology, 03 medical and health sciences, FEV1/FVC ratio, Rheumatology, Internal medicine, Severity of illness, medicine, Humans, Adverse effect, Systemic sclerosis, organ manifestations, prevalence, progression, smoking, Autoantibodies, Aged, 030203 arthritis & rheumatology, Scleroderma, Systemic, Heavy smoking, Group study, business.industry, Systemic/immunology/pathology/physiopathology, Lung/physiopathology, Non-Smokers, medicine.disease, respiratory tract diseases, Institutional repository, stomatognathic diseases, Logistic Models, 030228 respiratory system, Linear Models, business, Ex-Smokers, Smoking/immunology/pathology/physiopathology, DNA Topoisomerases
Abstract

ObjectiveMethodsData on the role of tobacco exposure in systemic sclerosis (SSc; scleroderma) severity and progression are scarce. We aimed to assess the effects of smoking on the evolution of pulmonary and skin manifestations, based on the European Scleroderma Trials and Research group database. Adult SSc patients with data on smoking history and a 12-24-month follow-up visit were included. Associations of severity and progression of organ involvement with smoking history and the Comprehensive Smoking Index were assessed using multivariable regression analyses. ResultsConclusionA total of 3,319 patients were included (mean age 57 years, 85% female); 66% were never smokers, 23% were ex-smokers, and 11% were current smokers. Current smokers had a lower percentage of antitopoisomerase autoantibodies than previous or never smokers (31% versus 40% and 45%, respectively). Never smokers had a higher baseline forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio than previous and current smokers (P < 0.001). The FEV1/FVC ratio declined faster in current smokers than in never smokers (P = 0.05) or ex-smokers (P = 0.01). The baseline modified Rodnan skin thickness score (MRSS) and the MRSS decline were comparable across smoking groups. Although heavy smoking (>25 pack-years) increased the odds of digital ulcers by almost 50%, there was no robust adverse association of smoking with digital ulcer development. The known adverse effect of smoking on bronchial airways and alveoli is also observed in SSc patients; however, robust adverse effects of smoking on the progression of SSc-specific pulmonary or cutaneous manifestations were not observed.

Published
2018

37. LINE-1 Evasion of Epigenetic Repression in Humans

Author

Sanchez-Luque, Francisco J., primary, Kempen, Marie-Jeanne H.C., additional, Gerdes, Patricia, additional, Vargas-Landin, Dulce B., additional, Richardson, Sandra R., additional, Troskie, Robin-Lee, additional, Jesuadian, J. Samuel, additional, Cheetham, Seth W., additional, Carreira, Patricia E., additional, Salvador-Palomeque, Carmen, additional, García-Cañadas, Marta, additional, Muñoz-Lopez, Martin, additional, Sanchez, Laura, additional, Lundberg, Mischa, additional, Macia, Angela, additional, Heras, Sara R., additional, Brennan, Paul M., additional, Lister, Ryan, additional, Garcia-Perez, Jose L., additional, Ewing, Adam D., additional, and Faulkner, Geoffrey J., additional

Published
2019
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38. Digital ulcers predict a worse disease course in patients with systemic sclerosis

Author

Mihai, Carina, Landewé, Robert, Van Der Heijde, Désirée, Walker, Ulrich A., Constantin, Paul I., Gherghe, Ana Maria, Ionescu, Ruxandra, Rednic, Simona, Allanore, Yannick, Avouac, Jéroˆme, Czirják, László, Hachulla, Eric, Riemekasten, Gabriela, Cozzi, Franco, Airò, Paolo, Cutolo, Maurizio, Mueller Ladner, Ulf, Matucci Cerinic, Marco, Launay, David, Dobrota, Rucsandra, Sfrent Cornateanu, Roxana, Zingarelli, Stefania, Pigatto, Erika, Cuomo, Giovanna, Caramaschi, Paola, Ananieva, Lidia, Ullman, Susanne, Iversen, Line, Gurman, Alexandra Balbir, Braun Moscovici, Yolanda, Carreira, Patricia E., Joven, Beatriz E., Minier, Tünde, Guiducci, Serena, Bellando Randone, Silvia, Pellerito, Raffaele, Hunzelmann, Nicolas, Tarner, Ingo H., Radominski, Sebastião Cezar, De Souza Müller, Carolina, Iannone, Florenzo, Henes, Jörg, Bancel, Dominique Farge, Damjanov, Nemanja, Ostojic, Predrag, Pozzi, Maria Rosa, Hesselstrand, Roger, Denton, Christopher, Krasowska, Dorota, Tikly, Mohammed, Riccieri, Valeria, Cantatore, Francesco Paolo, Corrado, Ada, Da Silva, José Antonio Pereira, Salvador, Maria João, Tyndall, Alan, Gabrielli, Armando, Distler, Oliver, Jordan, Suzan, Heitmann, Stefan, Burkhardt, Harald, Himsel, Andrea, Rozman, Blaz, Smith, Vanessa, Keyser, Filip De, Kalitena, Dusanka Martinovic, Radic, Mislav, Filipescu, Ileana, Petcu, Ana, Vlachoyiannopoulos, Panayiotis, Kucharz, Eugene J., Widuchowska, Malgorzata, Kopec Medrek, Magdalena, Kotulska, Anna, Szücs, Gabriella, Stankovic, Aleksandra, Stamenkovic, Bojana, Selmi, Carlo Francesco, Santis, Maria De, Marasini, Bianca, Coleiro, Bernard, Santamaria, Vera Ortiz, Westhovens, René, Becvár, Radim, Novak, Srdan, Engelhart, Merete, Meroni, Pierluigi, Ingegnoli, Francesca, Zeni, Silvana, Sulli, Alberto, Distler, Jörg, Yavuz, Sule, Montecucco, Carlomaurizio, Eyerich, Kilian, Krummel Lorenz, Brigitte, Zenone, Thierry, Midtvedt, Øyvind, Chizzolini, Carlo, Seidel, Matthias, Oleszowsky, Mara, Üprus, Maria, Opriş, Daniela, Groseanu, Laura, Bielecka, Otylia Kowal, Antonio, Zea Mendoza, Szechinski, Jacek, Morovic Vergles, Jadranka, Scorza, Raffaella, Puppo, Francesco, Mathieu, Alessandro, Anic, Branimir, Stork, Jiri, Stebbings, Simon, Inanc, Murat, Hasler, Paul, Von Mühlen, Carlos Alberto, Aringer, Martin, Popa, Sergei, Mengtao, Li, Rosato, Edoardo, University of Zurich, and Mihai, Carina

Subjects
Genetics and Molecular Biology (all), Lung Diseases, Male, 0301 basic medicine, Databases, Factual, Epidemiology, 2745 Rheumatology, Vital Capacity, Disease, Biochemistry, Scleroderma, Systemic autoimmune disease, High morbidity, 0302 clinical medicine, Cardiovascular Disease, Immunology and Allergy, Medicine (all), 10051 Rheumatology Clinic and Institute of Physical Medicine, Systemic Sclerosis, Adult, Aged, Cardiovascular Diseases, Disease Progression, Female, Hand Dermatoses, Humans, Hypertension, Pulmonary, Kidney Diseases, Middle Aged, Multivariate Analysis, Prognosis, Proportional Hazards Models, Pulmonary Diffusing Capacity, Retrospective Studies, Scleroderma, Systemic, Skin Ulcer, Stroke Volume, Fingers, Rheumatology, Immunology, Biochemistry, Genetics and Molecular Biology (all), Orvostudományok, Pulmonary, Hypertension, 2723 Immunology and Allergy, medicine.medical_specialty, 610 Medicine & health, Klinikai orvostudományok, General Biochemistry, Genetics and Molecular Biology, Disease course, Databases, 03 medical and health sciences, 1300 General Biochemistry, Genetics and Molecular Biology, Internal medicine, Cox proportional hazards regression, medicine, In patient, Factual, 030203 arthritis & rheumatology, 2403 Immunology, business.industry, Systemic, medicine.disease, 030104 developmental biology, Physical therapy, business
Abstract

ObjectiveSystemic sclerosis (SSc) is a systemic autoimmune disease with high morbidity and significant mortality. There is a great need of predictors that would allow risk stratification of patients with SSc and ultimately initiation of treatment early enough to ensure optimal clinical results. In this study, we evaluated whether a history of digital ulcers (HDU) at presentation may be a predictor of vascular outcomes and of overall clinical worsening and death in patients with SSc.MethodsPatients from the EULAR Scleroderma Trials and Research (EUSTAR) database, satisfying at inclusion the 1980 American College of Rheumatology classification criteria for SSc, who had a follow-up of at least 3 years since baseline or who have died, were included in the analysis. HDU at presentation as a predictor of disease worsening or death was evaluated by Cox proportional hazards regression analysis.Results3196 patients matched the inclusion criteria (male sex 13.2%, 33.4% diffuse subset). At presentation, 1092/3196 patients had an HDU (34.1%). In multivariable analysis adjusting for age, gender and all parameters considered potentially significant, HDU was predictive for the presence of active digital ulcers (DUs) at prospective visits (HR (95% CI)): 2.41 (1.91 to 3.03), pConclusionsIn patients with SSc, HDU at presentation predicts the occurrence of DUs at follow-up and is associated with cardiovascular worsening and decreased survival.

Published
2015

39. Incidences and risk factors of organ manifestations in the early course of systemic sclerosis: A longitudinal EUSTAR study

Author

Jaeger, Veronika K., Wirz, Elina G., Allanore, Yannick, Rossbach, Philipp, Riemekasten, Gabriela, Hachulla, Eric, Distler, Oliver, Airò, Paolo, Carreira, Patricia E., Gurman, Alexandra Balbir, Tikly, Mohammed, Vettori, Serena, Damjanov, Nemanja, Müller Ladner, Ulf, Distler, Jörg H. W., Mangtao, Li, Walker, Ulrich A., Ananieva, Lidia, Heitmann, Stefan, Rednic, Simona, Riccieri, Valeria, Szmyrka Kaczmarek, Magdalena, Farge, Dominique, Lapadula, Giovanni, Matucci Cerinic, Marco, Guiducci, Serena, Hunzelmann, Nicolas, Ricci, Massimo, Mihai, Carina, Veale, Douglas, Hesselstrand, Roger, Mariok, Eduardo, Smith, Vanessa, Tarner, Ingo H., Kucharz, Eugene J., Czirják, László, Martinovic, Duska, Solanki, Kamal, Ancuta, Codrina Mihaela, Sibilia, Jean, Paola, Caramaschi, Hassanien, Manal, Kahl, Sarah, Wigley, Frederick, Vanthuyne, Marie, Opris, Daniela, Radominski, Sebastião C., Monaco, Andrea Lo, Corrado, Ada, Koehm, Michaela, Codullo, Veronica, Radim, Bevcar, Loyo, Esthela, Üprus, Maria, Pellerito, Raffaele, Zenone, Thierry, Gabrielli, Armando, Kowal Bielecka, Otylia, Rozman, Blaz, Scorza, Raffaella, Saketkoo, Lesley Ann, Midtvedt, Oyvind, Von Mühlen, Carlos Alberto, Henes, Jörg, Branimir, Ani, Hasler, Paul, Yavuz, Sule, Adler, Sabine, Krummel Lorenz, Brigitte, Posa, Magdalena, Engelhart, Merete, Denton, Christopher, Krasowska, Dorota, Lefebvre, Paloma Garcia De La Peña, Cozzi, Franco, Mouthon, Luc, Rosato, Edoardo, Selmi, Carlo, Sancho, Juan José Alegre, Mallia, Carmel, Limonta, Massimiliano, Seidel, Matthias, Foti, Rosario, Stamp, Lisa, Ullman, Susanne, Stebbings, Simon, Santamaria, Vera Ortiz, Del Galdo, Francesco, De Langhe, Ellen, Mathieu, Alessandro, Sunderkötter, Cord, Eyerich, Kilian, Stamenkovic, Bojana, Novak, Srdan, Sampaio Barros, Percival D., Kayser, Cristiane, Litinsky, Ira, Couto, Maura, Jaeger, Veronika K., Wirz, Elina G., Allanore, Yannick, Rossbach, Philipp, Riemekasten, Gabriela, Hachulla, Eric, Distler, Oliver, Airã², Paolo, Carreira, Patricia E., Gurman, Alexandra Balbir, Tikly, Mohammed, Vettori, Serena, Damjanov, Nemanja, Mã¼ller ladner, Ulf, Distler, Jã¶rg H. W., Li, Mangtao, Walker, Ulrich A., Ananieva, Lidia, Heitmann, Stefan, Rednic, Simona, Riccieri, Valeria, Szmyrka kaczmarek, Magdalena, Farge, Dominique, Lapadula, Giovanni, Matucci cerinic, Marco, Guiducci, Serena, Hunzelmann, Nicola, Ricci, Massimo, Mihai, Carina, Veale, Dougla, Hesselstrand, Roger, Mariok, Eduardo, Smith, Vanessa, Tarner, Ingo H., Kucharz, Eugene J., Czirjã¡k, Lã¡szlã³, Martinovic, Duska, Solanki, Kamal, Ancuta, Codrina Mihaela, Sibilia, Jean, Paola, Caramaschi, Hassanien, Manal, Kahl, Sarah, Wigley, Frederick, Vanthuyne, Marie, Opris, Daniela, Radominski, Sebastiã£o C., Monaco, Andrea Lo, Corrado, Ada, Koehm, Michaela, Codullo, Veronica, Radim, Bevcar, Loyo, Esthela, Ãœprus, Maria, Pellerito, Raffaele, Zenone, Thierry, Gabrielli, Armando, Kowal bielecka, Otylia, Rozman, Blaz, Scorza, Raffaella, Saketkoo, Lesley Ann, Midtvedt, Oyvind, Von Mã¼hlen, Carlos Alberto, Henes, Jã¶rg, Branimir, Ani, Hasler, Paul, Yavuz, Sule, Adler, Sabine, Krummel lorenz, Brigitte, Posa, Magdalena, Engelhart, Merete, Denton, Christopher, Krasowska, Dorota, Lefebvre, Paloma Garcia De La Peã±a, Cozzi, Franco, Mouthon, Luc, Rosato, Edoardo, Selmi, Carlo, Sancho, Juan Josã© Alegre, Mallia, Carmel, Limonta, Massimiliano, Seidel, Matthia, Foti, Rosario, Stamp, Lisa, Ullman, Susanne, Stebbings, Simon, Santamaria, Vera Ortiz, Del Galdo, Francesco, De Langhe, Ellen, Mathieu, Alessandro, Sunderkã¶tter, Cord, Eyerich, Kilian, Stamenkovic, Bojana, Novak, Srdan, Sampaio barros, Percival D., Kayser, Cristiane, Litinsky, Ira, Couto, Maura, and University of Zurich

Subjects
Male, Genetics and Molecular Biology (all), Pulmonology, Blood Pressure, Vascular Medicine, Biochemistry, Scleroderma, Diagnostic Radiology, 0302 clinical medicine, Retrospective Studie, Longitudinal Studies, lcsh:Science, integumentary system, Incidence, Arteries, Systolic Pressure, 3. Good health, Echocardiography, Cohort, Regression Analysis, Human, medicine.medical_specialty, Imaging Techniques, Gastrointestinal Disease, Immunology, 1100 General Agricultural and Biological Sciences, Skin Diseases, 03 medical and health sciences, FEV1/FVC ratio, Rheumatology, 1300 General Biochemistry, Genetics and Molecular Biology, Humans, Autoantibodies, Retrospective Studies, Aged, 1000 Multidisciplinary, Biochemistry, Genetics and Molecular Biology (all), Proportional hazards model, lcsh:R, Biology and Life Sciences, Proteins, medicine.disease, Agricultural and Biological Sciences (all), Blood Vessels, lcsh:Q, Clinical Medicine, Ejection Fraction, Lung Diseases, Kidney Disease, Physiology, Gastrointestinal Diseases, lcsh:Medicine, Longitudinal Studie, Kaplan-Meier Estimate, Medicine (all), Lung Disease, Pericardial effusion, Risk Factors, Medizinische Fakultät, Immune Physiology, Ultrasound Imaging, Medicine and Health Sciences, 030212 general & internal medicine, Pulmonary Arteries, Connective Tissue Diseases, Immune System Proteins, Pulmonary Hypertension, Multidisciplinary, Ejection fraction, Radiology and Imaging, Incidence (epidemiology), 10051 Rheumatology Clinic and Institute of Physical Medicine, Middle Aged, Autoantibodie, Heart Disease, Kidney Diseases, Female, Anatomy, Research Article, Adult, Heart Diseases, Cardiology, 610 Medicine & health, Research and Analysis Methods, Antibodies, Regression Analysi, Autoimmune Diseases, Diagnostic Medicine, Internal medicine, medicine, ddc:610, 030203 arthritis & rheumatology, Scleroderma, Systemic, business.industry, Risk Factor, Skin Disease, Raynaud Disease, Retrospective cohort study, Surgery, Cardiovascular Anatomy, Clinical Immunology, business
Abstract

Objective Systemic sclerosis (SSc) is a rare and clinically heterogeneous autoimmune disorder characterised by fibrosis and microvascular obliteration of the skin and internal organs. Organ involvement mostly manifests after a variable period of the onset of Raynaud's phenomenon (RP). We aimed to map the incidence and predictors of pulmonary, cardiac, gastrointestinal (GI) and renal involvement in the early course of SSc. Methods In the EUSTAR cohort, patients with early SSc were identified as those who had a visit within the first year after RP onset. Incident SSc organ manifestations and their risk factors were assessed using Kaplan-Meier methods and Cox regression analysis. Results Of the 695 SSc patients who had a baseline visit within 1 year after RP onset, the incident non-RP manifestations (in order of frequency) were: skin sclerosis (75%) GI symptoms (71%), impaired diffusing capacity for monoxide40mmHg (14%), and renal crisis (3%). In the heart, incidence rates were highest for diastolic dysfunction, followed by conduction blocks and pericardial effusion. While the main baseline risk factor for a short timespan to develop FVC impairment was diffuse skin involvement, for PAPsys>40mmHg it was higher patient age. The main risk factors for incident cardiac manifestations were anti-topoisomerase autoantibody positivity and older age. Male sex, anti-RNA-polymerase-III positivity, and older age were risk factors associated with incident renal crisis. Conclusion In SSc patients presenting early after RP onset, approximately half of all incident organ manifestations occur within 2 years and have a simultaneous rather than a sequential onset. These findings have implications for the design of new diagnostic and therapeutic strategies aimed to ‘widen' the still very narrow ‘window of opportunity'. They may also enable physicians to counsel and manage patients presenting early in the course of SSc more accurately.

Published
2016

40. Disability, fatigue, pain and their associates in early diffuse cutaneous systemic sclerosis:the European Scleroderma Observational Study

Author

Peytrignet, Sébastien, Denton, Christopher P, Lunt, Mark, Hesselstrand, Roger, Mouthon, Luc, Silman, Alan, Pan, Xiaoyan, Brown, Edith, Czirják, László, Distler, Jörg H W, Distler, Oliver, Fligelstone, Kim, Gregory, William J, Ochiel, Rachel, Vonk, Madelon, Ancuta, Codrina, Ong, Voon H, Farge, Dominique, Hudson, Marie, Matucci-Cerinic, Marco, Balbir-Gurman, Alexandra, Midtvedt, Øyvind, Jordan, Alison C, Stevens, Wendy, Moinzadeh, Pia, Hall, Frances C, Agard, Christian, Anderson, Marina E, Diot, Elisabeth, Madhok, Rajan, Akil, Mohammed, Buch, Maya H, Chung, Lorinda, Damjanov, Nemanja, Gunawardena, Harsha, Lanyon, Peter, Ahmad, Yasmeen, Chakravarty, Kuntal, Jacobsen, Søren, MacGregor, Alexander J, McHugh, Neil, Müller-Ladner, Ulf, Riemekasten, Gabriela, Becker, Michael, Roddy, Janet, Carreira, Patricia E, Fauchais, Anne Laure, Hachulla, Eric, Hamilton, Jennifer, Inanç, Murat, McLaren, John S, van Laar, Jacob M, Pathare, Sanjay, Proudman, Susanna, Rudin, Anna, Sahhar, Joanne, Coppere, Brigitte, Serratrice, Christine, Sheeran, Tom, Veale, Douglas J, Grange, Claire, Trad, Georges-Selim, Herrick, Ariane L, Peytrignet, Sébastien, Denton, Christopher P, Lunt, Mark, Hesselstrand, Roger, Mouthon, Luc, Silman, Alan, Pan, Xiaoyan, Brown, Edith, Czirják, László, Distler, Jörg H W, Distler, Oliver, Fligelstone, Kim, Gregory, William J, Ochiel, Rachel, Vonk, Madelon, Ancuta, Codrina, Ong, Voon H, Farge, Dominique, Hudson, Marie, Matucci-Cerinic, Marco, Balbir-Gurman, Alexandra, Midtvedt, Øyvind, Jordan, Alison C, Stevens, Wendy, Moinzadeh, Pia, Hall, Frances C, Agard, Christian, Anderson, Marina E, Diot, Elisabeth, Madhok, Rajan, Akil, Mohammed, Buch, Maya H, Chung, Lorinda, Damjanov, Nemanja, Gunawardena, Harsha, Lanyon, Peter, Ahmad, Yasmeen, Chakravarty, Kuntal, Jacobsen, Søren, MacGregor, Alexander J, McHugh, Neil, Müller-Ladner, Ulf, Riemekasten, Gabriela, Becker, Michael, Roddy, Janet, Carreira, Patricia E, Fauchais, Anne Laure, Hachulla, Eric, Hamilton, Jennifer, Inanç, Murat, McLaren, John S, van Laar, Jacob M, Pathare, Sanjay, Proudman, Susanna, Rudin, Anna, Sahhar, Joanne, Coppere, Brigitte, Serratrice, Christine, Sheeran, Tom, Veale, Douglas J, Grange, Claire, Trad, Georges-Selim, and Herrick, Ariane L

Abstract

Objectives: Our aim was to describe the burden of early dcSSc in terms of disability, fatigue and pain in the European Scleroderma Observational Study cohort, and to explore associated clinical features.Methods: Patients completed questionnaires at study entry, 12 and 24 months, including the HAQ disability index (HAQ-DI), the Cochin Hand Function Scale (CHFS), the Functional Assessment of Chronic Illness Therapy-fatigue and the Short Form 36 (SF36). Associates examined included the modified Rodnan skin score (mRSS), current digital ulcers and internal organ involvement. Correlations between 12-month changes were also examined.Results: The 326 patients recruited (median disease duration 11.9 months) displayed high levels of disability [mean (s.d.) HAQ-DI 1.1 (0.83)], with 'grip' and 'activity' being most affected. Of the 18 activities assessed in the CHFS, those involving fine finger movements were most affected. High HAQ-DI and CHFS scores were both associated with high mRSS (ρ = 0.34, P < 0.0001 and ρ = 0.35, P < 0.0001, respectively). HAQ-DI was higher in patients with digital ulcers (P = 0.004), pulmonary fibrosis (P = 0.005), cardiac (P = 0.005) and muscle involvement (P = 0.002). As anticipated, HAQ-DI, CHFS, the Functional Assessment of Chronic Illness Therapy and SF36 scores were all highly correlated, in particular the HAQ-DI with the CHFS (ρ = 0.84, P < 0.0001). Worsening HAQ-DI over 12 months was strongly associated with increasing mRSS (ρ = 0.40, P < 0.0001), decreasing hand function (ρ = 0.57, P < 0.0001) and increasing fatigue (ρ = -0.53, P < 0.0001).Conclusion: The European Scleroderma Observational Study highlights the burden of disability in early dcSSc, with high levels of disability and fatigue, associating with the degree of skin thickening (mRSS). Impaired hand function is a major contributor to overall disability.

Published
2018

41. Disability, fatigue, pain and their associates in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study

Author

Peytrignet, Sebastien, Denton, Christopher P., Lunt, Mark, Hesselstrand, Roger, Mouthon, Luc, Silman, Alan, Pan, Xiaoyan, Brown, Edith, Czirjak, Laszlo, Distler, Jorg H. W., Distler, Oliver, Fligelstone, Kim, Gregory, William J., Ochiel, Rachel, Vonk, Madelon, Ancuta, Codrina, Ong, Voon H., Farge, Dominique, Hudson, Marie, Matucci-Cerinic, Marco, Balbir-Gurman, Alexandra, Midtvedt, Oyvind, Jordan, Alison C., Stevens, Wendy, Moinzadeh, Pia, Hall, Frances C., Agard, Christian, Anderson, Marina E., Diot, Elisabeth, Madhok, Rajan, Akil, Mohammed, Buch, Maya H., Chung, Lorinda, Damjanov, Nemanja, Gunawardena, Harsha, Lanyon, Peter, Ahmad, Yasmeen, Chakravarty, Kuntal, Jacobsen, Soren, MacGregor, Alexander J., McHugh, Neil, Muller-Ladner, Ulf, Riemekasten, Gabriela, Becker, Michael, Roddy, Janet, Carreira, Patricia E., Fauchais, Anne Laure, Hachulla, Eric, Hamilton, Jennifer, Inanc, Murat, McLaren, John S., van Laar, Jacob M., Pathare, Sanjay, Proudman, Susanna, Rudin, Anna, Sahhar, Joanne, Coppere, Brigitte, Serratrice, Christine, Sheeran, Tom, Veale, Douglas J., Grange, Claire, Trad, Georges-Selim, Herrick, Ariane L., Peytrignet, Sebastien, Denton, Christopher P., Lunt, Mark, Hesselstrand, Roger, Mouthon, Luc, Silman, Alan, Pan, Xiaoyan, Brown, Edith, Czirjak, Laszlo, Distler, Jorg H. W., Distler, Oliver, Fligelstone, Kim, Gregory, William J., Ochiel, Rachel, Vonk, Madelon, Ancuta, Codrina, Ong, Voon H., Farge, Dominique, Hudson, Marie, Matucci-Cerinic, Marco, Balbir-Gurman, Alexandra, Midtvedt, Oyvind, Jordan, Alison C., Stevens, Wendy, Moinzadeh, Pia, Hall, Frances C., Agard, Christian, Anderson, Marina E., Diot, Elisabeth, Madhok, Rajan, Akil, Mohammed, Buch, Maya H., Chung, Lorinda, Damjanov, Nemanja, Gunawardena, Harsha, Lanyon, Peter, Ahmad, Yasmeen, Chakravarty, Kuntal, Jacobsen, Soren, MacGregor, Alexander J., McHugh, Neil, Muller-Ladner, Ulf, Riemekasten, Gabriela, Becker, Michael, Roddy, Janet, Carreira, Patricia E., Fauchais, Anne Laure, Hachulla, Eric, Hamilton, Jennifer, Inanc, Murat, McLaren, John S., van Laar, Jacob M., Pathare, Sanjay, Proudman, Susanna, Rudin, Anna, Sahhar, Joanne, Coppere, Brigitte, Serratrice, Christine, Sheeran, Tom, Veale, Douglas J., Grange, Claire, Trad, Georges-Selim, and Herrick, Ariane L.

Abstract

Objectives. Our aim was to describe the burden of early dcSSc in terms of disability, fatigue and pain in the European Scleroderma Observational Study cohort, and to explore associated clinical features. Methods. Patients completed questionnaires at study entry, 12 and 24 months, including the HAQ disability index (HAQ-DI), the Cochin Hand Function Scale (CHFS), the Functional Assessment of Chronic Illness Therapy-fatigue and the Short Form 36 (SF36). Associates examined included the modified Rodnan skin score (mRSS), current digital ulcers and internal organ involvement. Correlations between 12-month changes were also examined. Results. The 326 patients recruited (median disease duration 11.9 months) displayed high levels of disability [mean (s.d.) HAQ-DI 1.1 (0.83)], with 'grip' and 'activity' being most affected. Of the 18 activities assessed in the CHFS, those involving fine finger movements were most affected. High HAQ-DI and CHFS scores were both associated with high mRSS (rho = 0.34, P < 0.0001 and rho = 0.35, P < 0.0001, respectively). HAQ-DI was higher in patients with digital ulcers (P = 0.004), pulmonary fibrosis (P = 0.005), cardiac (P = 0.005) and muscle involvement (P = 0.002). As anticipated, HAQ-DI, CHFS, the Functional Assessment of Chronic Illness Therapy and SF36 scores were all highly correlated, in particular the HAQ-DI with the CHFS (rho = 0.84, P < 0.0001). Worsening HAQ-DI over 12 months was strongly associated with increasing mRSS (rho = 0.40, P < 0.0001), decreasing hand function (rho = 0.57, P < 0.0001) and increasing fatigue (rho = -0.53, P < 0.0001). Conclusion.The European Scleroderma Observational Study highlights the burden of disability in early dcSSc, with high levels of disability and fatigue, associating with the degree of skin thickening (mRSS). Impaired hand function is a major contributor to overall disability.

Published
2018

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

Author

Herrick, Ariane L., Peytrignet, Sebastien, Lunt, Mark, Pan, Xiaoyan, Hesselstrand, Roger, Mouthon, Luc, Silman, Alan J., Dinsdale, Graham, Brown, Edith, Czirjak, Laszlo, Distler, Joerg H. W., Distler, Oliver, Fligelstone, Kim, Gregory, William J., Ochiel, Rachel, Vonk, Madelon C., Ancuta, Codrina, Ong, Voon H., Farge, Dominique, Hudson, Marie, Matucci-Cerinic, Marco, Balbir-Gurman, Alexandra, Midtvedt, Oyvind, Jobanputra, Paresh, Jordan, Alison C., Stevens, Wendy, Moinzadeh, Pia, Hall, Frances C., Agard, Christian, Anderson, Marina E., Diot, Elisabeth, Madhok, Rajan, Akil, Mohammed, Buch, Maya H., Chung, Lorinda, Damjanov, Nemanja S., Gunawardena, Harsha, Lanyon, Peter, Ahmad, Yasmeen, Chakravarty, Kuntal, Jacobsen, Soren, MacGregor, Alexander J., McHugh, Neil, Mueller-Ladner, Ulf, Riemekasten, Gabriela, Becker, Michael, Roddy, Janet, Carreira, Patricia E., Fauchais, Anne Laure, Hachulla, Eric, Hamilton, Jennifer, Inanc, Murat, McLaren, John S., van Laar, Jacob M., Pathare, Sanjay, Proudman, Susanna M., Rudin, Anna, Sahhar, Joanne, Coppere, Brigitte, Serratrice, Christine, Sheeran, Tom, Veale, Douglas J., Grange, Claire, Trad, Georges-Selim, Denton, Christopher P., Herrick, Ariane L., Peytrignet, Sebastien, Lunt, Mark, Pan, Xiaoyan, Hesselstrand, Roger, Mouthon, Luc, Silman, Alan J., Dinsdale, Graham, Brown, Edith, Czirjak, Laszlo, Distler, Joerg H. W., Distler, Oliver, Fligelstone, Kim, Gregory, William J., Ochiel, Rachel, Vonk, Madelon C., Ancuta, Codrina, Ong, Voon H., Farge, Dominique, Hudson, Marie, Matucci-Cerinic, Marco, Balbir-Gurman, Alexandra, Midtvedt, Oyvind, Jobanputra, Paresh, Jordan, Alison C., Stevens, Wendy, Moinzadeh, Pia, Hall, Frances C., Agard, Christian, Anderson, Marina E., Diot, Elisabeth, Madhok, Rajan, Akil, Mohammed, Buch, Maya H., Chung, Lorinda, Damjanov, Nemanja S., Gunawardena, Harsha, Lanyon, Peter, Ahmad, Yasmeen, Chakravarty, Kuntal, Jacobsen, Soren, MacGregor, Alexander J., McHugh, Neil, Mueller-Ladner, Ulf, Riemekasten, Gabriela, Becker, Michael, Roddy, Janet, Carreira, Patricia E., Fauchais, Anne Laure, Hachulla, Eric, Hamilton, Jennifer, Inanc, Murat, McLaren, John S., van Laar, Jacob M., Pathare, Sanjay, Proudman, Susanna M., Rudin, Anna, Sahhar, Joanne, Coppere, Brigitte, Serratrice, Christine, Sheeran, Tom, Veale, Douglas J., Grange, Claire, Trad, Georges-Selim, and Denton, Christopher P.

Abstract

Objectives Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs). Methods The modified Rodnan skin score (mRSS) was recorded every 3months 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.

Published
2018

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

Author

Herrick, Ariane L, Peytrignet, Sebastien, Lunt, Mark, Pan, Xiaoyan, Hesselstrand, Roger, Mouthon, Luc, Silman, Alan J, Dinsdale, Graham, Brown, Edith, Czirják, László, Distler, Jörg H W, Distler, Oliver, Fligelstone, Kim, Gregory, William J, Ochiel, Rachel, Vonk, Madelon C, Ancuţa, Codrina, Ong, Voon H, Farge, Dominique, Hudson, Marie, Matucci-Cerinic, Marco, Balbir-Gurman, Alexandra, Midtvedt, Øyvind, Jobanputra, Paresh, Jordan, Alison C, Stevens, Wendy, Moinzadeh, Pia, Hall, Frances C, Agard, Christian, Anderson, Marina E, Diot, Elisabeth, Madhok, Rajan, Akil, Mohammed, Buch, Maya H, Chung, Lorinda, Damjanov, Nemanja S, Gunawardena, Harsha, Lanyon, Peter, Ahmad, Yasmeen, Chakravarty, Kuntal, Jacobsen, Søren, MacGregor, Alexander J, McHugh, Neil, Müller-Ladner, Ulf, Riemekasten, Gabriela, Becker, Michael, Roddy, Janet, Carreira, Patricia E, Fauchais, Anne Laure, Hachulla, Eric, Hamilton, Jennifer, İnanç, Murat, McLaren, John S, van Laar, Jacob M, Pathare, Sanjay, Proudman, Susanna M, Rudin, Anna, Sahhar, Joanne, Coppere, Brigitte, Serratrice, Christine, Sheeran, Tom, Veale, Douglas J, Grange, Claire, Trad, Georges-Selim, Denton, Christopher P, Herrick, Ariane L, Peytrignet, Sebastien, Lunt, Mark, Pan, Xiaoyan, Hesselstrand, Roger, Mouthon, Luc, Silman, Alan J, Dinsdale, Graham, Brown, Edith, Czirják, László, Distler, Jörg H W, Distler, Oliver, Fligelstone, Kim, Gregory, William J, Ochiel, Rachel, Vonk, Madelon C, Ancuţa, Codrina, Ong, Voon H, Farge, Dominique, Hudson, Marie, Matucci-Cerinic, Marco, Balbir-Gurman, Alexandra, Midtvedt, Øyvind, Jobanputra, Paresh, Jordan, Alison C, Stevens, Wendy, Moinzadeh, Pia, Hall, Frances C, Agard, Christian, Anderson, Marina E, Diot, Elisabeth, Madhok, Rajan, Akil, Mohammed, Buch, Maya H, Chung, Lorinda, Damjanov, Nemanja S, Gunawardena, Harsha, Lanyon, Peter, Ahmad, Yasmeen, Chakravarty, Kuntal, Jacobsen, Søren, MacGregor, Alexander J, McHugh, Neil, Müller-Ladner, Ulf, Riemekasten, Gabriela, Becker, Michael, Roddy, Janet, Carreira, Patricia E, Fauchais, Anne Laure, Hachulla, Eric, Hamilton, Jennifer, İnanç, Murat, McLaren, John S, van Laar, Jacob M, Pathare, Sanjay, Proudman, Susanna M, Rudin, Anna, Sahhar, Joanne, Coppere, Brigitte, Serratrice, Christine, Sheeran, Tom, Veale, Douglas J, Grange, Claire, Trad, Georges-Selim, and Denton, Christopher P

Abstract

OBJECTIVES: Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs).METHODS: The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. 'Progressors' were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV).RESULTS: 66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%.CONCLUSIONS: Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years.TRIAL REGISTRATION NUMBER: NCT02339441.

Published
2018

44. ACE inhibitors in SSc patients display a risk factor for scleroderma renal crisis—a EUSTAR analysis.

Author

Bütikofer, Lukas, Varisco, Pierre A., Distler, O., Kowal-Bielecka, O., Allanore, Y., Riemekasten, G., Villiger, P. M., Adler, S., on behalf of EUSTAR collaborators, Avouac, Jérôme, Walker, Ulrich A., Guiducci, Serena, Riemekasten, Gabriele, Airò, Paolo, Hachulla, Eric, Valentini, Gabriele, Carreira, Patricia E., Cozzi, Franco, Gurman, Alexandra Balbir, and Braun-Moscovici, Yolanda

Published
2020
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45. L1 Retrotransposon Heterogeneity in Ovarian Tumor Cell Evolution

Author

Nguyen, Thu H.M., primary, Carreira, Patricia E., additional, Sanchez-Luque, Francisco J., additional, Schauer, Stephanie N., additional, Fagg, Allister C., additional, Richardson, Sandra R., additional, Davies, Claire M., additional, Jesuadian, J. Samuel, additional, Kempen, Marie-Jeanne H.C., additional, Troskie, Robin-Lee, additional, James, Cini, additional, Beaven, Elizabeth A., additional, Wallis, Tristan P., additional, Coward, Jermaine I.G., additional, Chetty, Naven P., additional, Crandon, Alexander J., additional, Venter, Deon J., additional, Armes, Jane E., additional, Perrin, Lewis C., additional, Hooper, John D., additional, Ewing, Adam D., additional, Upton, Kyle R., additional, and Faulkner, Geoffrey J., additional

Published
2018
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46. L1 retrotransposition is a common feature of mammalian hepatocarcinogenesis

Author

Schauer, Stephanie N., primary, Carreira, Patricia E., additional, Shukla, Ruchi, additional, Gerhardt, Daniel J., additional, Gerdes, Patricia, additional, Sanchez-Luque, Francisco J., additional, Nicoli, Paola, additional, Kindlova, Michaela, additional, Ghisletti, Serena, additional, Santos, Alexandre Dos, additional, Rapoud, Delphine, additional, Samuel, Didier, additional, Faivre, Jamila, additional, Ewing, Adam D., additional, Richardson, Sandra R., additional, and Faulkner, Geoffrey J., additional

Published
2018
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47. Disability, fatigue, pain and their associates in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study

Author

Peytrignet, Sébastien, primary, Denton, Christopher P, additional, Lunt, Mark, additional, Hesselstrand, Roger, additional, Mouthon, Luc, additional, Silman, Alan, additional, Pan, Xiaoyan, additional, Brown, Edith, additional, Czirják, László, additional, Distler, Jörg H W, additional, Distler, Oliver, additional, Fligelstone, Kim, additional, Gregory, William J, additional, Ochiel, Rachel, additional, Vonk, Madelon, additional, Ancuţa, Codrina, additional, Ong, Voon H, additional, Farge, Dominique, additional, Hudson, Marie, additional, Matucci-Cerinic, Marco, additional, Balbir-Gurman, Alexandra, additional, Midtvedt, Øyvind, additional, Jordan, Alison C, additional, Stevens, Wendy, additional, Moinzadeh, Pia, additional, Hall, Frances C, additional, Agard, Christian, additional, Anderson, Marina E, additional, Diot, Elisabeth, additional, Madhok, Rajan, additional, Akil, Mohammed, additional, Buch, Maya H, additional, Chung, Lorinda, additional, Damjanov, Nemanja, additional, Gunawardena, Harsha, additional, Lanyon, Peter, additional, Ahmad, Yasmeen, additional, Chakravarty, Kuntal, additional, Jacobsen, Søren, additional, MacGregor, Alexander J, additional, McHugh, Neil, additional, Müller-Ladner, Ulf, additional, Riemekasten, Gabriela, additional, Becker, Michael, additional, Roddy, Janet, additional, Carreira, Patricia E, additional, Fauchais, Anne Laure, additional, Hachulla, Eric, additional, Hamilton, Jennifer, additional, İnanç, Murat, additional, McLaren, John S, additional, van Laar, Jacob M, additional, Pathare, Sanjay, additional, Proudman, Susanna, additional, Rudin, Anna, additional, Sahhar, Joanne, additional, Coppere, Brigitte, additional, Serratrice, Christine, additional, Sheeran, Tom, additional, Veale, Douglas J, additional, Grange, Claire, additional, Trad, Georges-Selim, additional, and Herrick, Ariane L, additional

Published
2017
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48. Treatment outcome in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study (ESOS)

Author

Herrick, Ariane L., Pan, Xiaoyan, Peytrignet, Sebastien, Lunt, Mark, Hesselstrand, Roger, Mouthon, Luc, Silman, Alan, Brown, Edith, Czirjak, Laszlo, Distler, Joerg H. W., Distler, Oliver, Fligelstone, Kim, Gregory, William J., Ochiel, Rachel, Vonk, Madelon, Ancuta, Codrina, Ong, Voon H., Farge, Dominique, Hudson, Marie, Matucci-Cerinic, Marco, Balbir-Gurman, Alexandra, Midtvedt, Oyvind, Jordan, Alison C., Jobanputra, Paresh, Stevens, Wendy, Moinzadeh, Pia, Hall, Frances C., Agard, Christian, Anderson, Marina E., Diot, Elisabeth, Madhok, Rajan, Akil, Mohammed, Buch, Maya H., Chung, Lorinda, Damjanov, Nemanja, Gunawardena, Harsha, Lanyon, Peter, Ahmad, Yasmeen, Chakravarty, Kuntal, Jacobsen, Soren, MacGregor, Alexander J., McHugh, Neil, Mueller-Ladner, Ulf, Riemekasten, Gabriela, Becker, Michael, Roddy, Janet, Carreira, Patricia E., Fauchais, Anne Laure, Hachulla, Eric, Hamilton, Jennifer, Inanc, Murat, McLaren, John S., van Laar, Jacob M., Pathare, Sanjay, Proudman, Susannah, Rudin, Anna, Sahhar, Joanne, Coppere, Brigitte, Serratrice, Christine, Sheeran, Tom, Veale, Douglas J., Grange, Claire, Trad, Georges-Selim, Denton, Christopher P., Herrick, Ariane L., Pan, Xiaoyan, Peytrignet, Sebastien, Lunt, Mark, Hesselstrand, Roger, Mouthon, Luc, Silman, Alan, Brown, Edith, Czirjak, Laszlo, Distler, Joerg H. W., Distler, Oliver, Fligelstone, Kim, Gregory, William J., Ochiel, Rachel, Vonk, Madelon, Ancuta, Codrina, Ong, Voon H., Farge, Dominique, Hudson, Marie, Matucci-Cerinic, Marco, Balbir-Gurman, Alexandra, Midtvedt, Oyvind, Jordan, Alison C., Jobanputra, Paresh, Stevens, Wendy, Moinzadeh, Pia, Hall, Frances C., Agard, Christian, Anderson, Marina E., Diot, Elisabeth, Madhok, Rajan, Akil, Mohammed, Buch, Maya H., Chung, Lorinda, Damjanov, Nemanja, Gunawardena, Harsha, Lanyon, Peter, Ahmad, Yasmeen, Chakravarty, Kuntal, Jacobsen, Soren, MacGregor, Alexander J., McHugh, Neil, Mueller-Ladner, Ulf, Riemekasten, Gabriela, Becker, Michael, Roddy, Janet, Carreira, Patricia E., Fauchais, Anne Laure, Hachulla, Eric, Hamilton, Jennifer, Inanc, Murat, McLaren, John S., van Laar, Jacob M., Pathare, Sanjay, Proudman, Susannah, Rudin, Anna, Sahhar, Joanne, Coppere, Brigitte, Serratrice, Christine, Sheeran, Tom, Veale, Douglas J., Grange, Claire, Trad, Georges-Selim, and Denton, Christopher P.

Abstract

Objectives The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches. Methods This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival. Results Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: -4.0 (-5.2 to -2.7) units for methotrexate, -4.1 (-5.3 to -2.9) for MMF, -3.3 (-4.9 to -1.7) for cyclophosphamide and -2.2 (-4.0 to -0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months. Conclusions These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed.

Published
2017

49. Value of systolic pulmonary arterial pressure as a prognostic factor of death in the systemic sclerosis EUSTAR population

Author

Hachulla, Eric, Clerson, Pierre, Airò, Paolo, Cuomo, Giovanna, Allanore, Yannick, Caramaschi, Paola, Rosato, Edoardo, Carreira, Patricia E., Riccieri, Valeria, Sarraco, Marta, Denton, Christopher P., Riemekasten, Gabriela, Pozzi, Maria Rosa, Zeni, Silvana, Mihai, Carmen Marina, Ullman, Susanne, Distler, Oliver, Rednic, Simona, Smith, Vanessa, Walker, Ulrich A., Matucci-Cerinic, Marco, Müller-Ladner, Ulf, Launay, David, Hachulla, Eric, Clerson, Pierre, Airò, Paolo, Cuomo, Giovanna, Allanore, Yannick, Caramaschi, Paola, Rosato, Edoardo, Carreira, Patricia E., Riccieri, Valeria, Sarraco, Marta, Denton, Christopher P., Riemekasten, Gabriela, Pozzi, Maria Rosa, Zeni, Silvana, Mihai, Carmen Marina, Ullman, Susanne, Distler, Oliver, Rednic, Simona, Smith, Vanessa, Walker, Ulrich A., Matucci-Cerinic, Marco, Müller-Ladner, Ulf, and Launay, David

Abstract

Objective. The aim of this study was to assess the prognostic value of systolic pulmonary artery pressure (sPAP) estimated by echocardiography in the multinational European League Against Rheumatism Scleroderma Trial and Research (EUSTAR) cohort. Methods. Data for patients with echocardiography documented between 1 January 2005 and 31 December 2011 were extracted from the EUSTAR database. Stepwise forward multivariable statistical Cox pulmonary hypertension analysis was used to examine the independent effect on survival of selected variables. Results. Based on our selection criteria, 1476 patients were included in the analysis; 87% of patients were female, with a mean age of 56.3 years (s.d. 13.5) and 31% had diffuse SSc. The mean duration of follow-up was 2.0 years (s.d. 1.2, median 1.9). Taking index sPAP of <30 mmHg as reference, the hazard ratio (HR) for death was 1.67 (95% CI 0.92, 2.96) if the index sPAP was between 30 and 36 mmHg, 2.37 (95% CI 1.14, 4.93) for sPAP between 36 and 40 mmHg, 3.72 (95% CI 1.61, 8.60) for sPAP between 40 and 50 mmHg and 9.75 (95% CI 4.98, 19.09) if sPAP was >50 mmHg. In a multivariable Cox model, sPAP and the diffusing capacity for carbon monoxide (DLCO) were independently associated with the risk of death [HR 1.833 (95% CI 1.035, 3.247) and HR 0.973 (95% CI 0.955, 0.991), respectively]. sPAP was an independent risk factor for death with a HR of 3.02 (95% CI 1.91, 4.78) for sPAP ≥36 mmHg. Conclusion. An estimated sPAP >36 mmHg at baseline echocardiography was significantly and independently associated with reduced survival, regardless of the presence of pulmonary hypertension based on right heart catheterization

Published
2017

50. Treatment outcome in early diffuse cutaneous systemic sclerosis:the European Scleroderma Observational Study (ESOS)

Author

Herrick, Ariane L, Pan, Xiaoyan, Peytrignet, Sébastien, Lunt, Mark, Hesselstrand, Roger, Mouthon, Luc, Silman, Alan, Brown, Edith, Czirják, László, Distler, Jörg H W, Distler, Oliver, Fligelstone, Kim, Gregory, William J, Ochiel, Rachel, Vonk, Madelon, Ancuţa, Codrina, Ong, Voon H, Farge, Dominique, Hudson, Marie, Matucci-Cerinic, Marco, Balbir-Gurman, Alexandra, Midtvedt, Øyvind, Jordan, Alison C, Jobanputra, Paresh, Stevens, Wendy, Moinzadeh, Pia, Hall, Frances C, Agard, Christian, Anderson, Marina E, Diot, Elisabeth, Madhok, Rajan, Akil, Mohammed, Buch, Maya H, Chung, Lorinda, Damjanov, Nemanja, Gunawardena, Harsha, Lanyon, Peter, Ahmad, Yasmeen, Chakravarty, Kuntal, Jacobsen, Søren, MacGregor, Alexander J, McHugh, Neil, Müller-Ladner, Ulf, Riemekasten, Gabriela, Becker, Michael, Roddy, Janet, Carreira, Patricia E, Fauchais, Anne Laure, Hachulla, Eric, Hamilton, Jennifer, Inanc, Murat, McLaren, John S, van Laar, Jacob M, Pathare, Sanjay, Proudman, Susannah, Rudin, Anna, Sahhar, Joanne, Coppere, Brigitte, Serratrice, Christine, Sheeran, Tom, Veale, Douglas J, Grange, Claire, Trad, Georges-Selim, Denton, Christopher P, Herrick, Ariane L, Pan, Xiaoyan, Peytrignet, Sébastien, Lunt, Mark, Hesselstrand, Roger, Mouthon, Luc, Silman, Alan, Brown, Edith, Czirják, László, Distler, Jörg H W, Distler, Oliver, Fligelstone, Kim, Gregory, William J, Ochiel, Rachel, Vonk, Madelon, Ancuţa, Codrina, Ong, Voon H, Farge, Dominique, Hudson, Marie, Matucci-Cerinic, Marco, Balbir-Gurman, Alexandra, Midtvedt, Øyvind, Jordan, Alison C, Jobanputra, Paresh, Stevens, Wendy, Moinzadeh, Pia, Hall, Frances C, Agard, Christian, Anderson, Marina E, Diot, Elisabeth, Madhok, Rajan, Akil, Mohammed, Buch, Maya H, Chung, Lorinda, Damjanov, Nemanja, Gunawardena, Harsha, Lanyon, Peter, Ahmad, Yasmeen, Chakravarty, Kuntal, Jacobsen, Søren, MacGregor, Alexander J, McHugh, Neil, Müller-Ladner, Ulf, Riemekasten, Gabriela, Becker, Michael, Roddy, Janet, Carreira, Patricia E, Fauchais, Anne Laure, Hachulla, Eric, Hamilton, Jennifer, Inanc, Murat, McLaren, John S, van Laar, Jacob M, Pathare, Sanjay, Proudman, Susannah, Rudin, Anna, Sahhar, Joanne, Coppere, Brigitte, Serratrice, Christine, Sheeran, Tom, Veale, Douglas J, Grange, Claire, Trad, Georges-Selim, and Denton, Christopher P

Abstract

OBJECTIVES: The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches.METHODS: This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival.RESULTS: Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: -4.0 (-5.2 to -2.7) units for methotrexate, -4.1 (-5.3 to -2.9) for MMF, -3.3 (-4.9 to -1.7) for cyclophosphamide and -2.2 (-4.0 to -0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months.CONCLUSIONS: These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed.TRIAL REGISTRATION NUMBER: NCT02339441.

Published
2017

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