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

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.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.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 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.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

Racial differences in systemic sclerosis disease presentation: a European Scleroderma Trials and Research group study

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

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

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

Study aim was to evaluate estimated glomerular filtration rate (eGFR), its association with clinical disease and its predictive ability with mortality in systemic sclerosis (SSc) patients from the European Scleroderma Trials and Research Group (EUSTAR) database

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

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 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 catheterizatio

Digital ulcers predict a worse disease course in patients with systemic sclerosis

none120noneMihai, 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; Li, Mengtao; Rosato, EdoardoMihai, 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; DE SANTIS, MARIA LINA; 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; Li, Mengtao; Rosato, Edoard

Phenotype of limited cutaneous systemic sclerosis patients with positive anti-topoisomerase I antibodies: data from EUSTAR cohort

OBJECTIVES: To characterize patients with positive anti-topoisomerase I (ATA) in lcSSc. METHODS: SSc patients enrolled in the EUSTAR cohort with a disease duration of ≤3 years at database entry were considered. We assessed the risk of major organ involvement in the following groups: ATA-lcSSc vs ACA-lcSSc and vs ANA without specificity (ANA)-lcSSc, and ATA-lcSSc vs ATA-dcSSc. Cox regression models with time-dependent covariates were performed with the following outcomes: new-onset interstitial lung disease (ILD), ILD progression [forced vital capacity (FVC) decline ≥10% and ≥5% vs values at ILD diagnosis), primary myocardial involvement (PMI), pulmonary hypertension (PH), any organ involvement and all-cause mortality. RESULTS: We included 1252 patients [194 ATA-lcSSc (15.5%)], with 7.7 years (s.d. 3.5) of follow-up. ILD risk was higher in ATA-lcSSc vs ACA- and ANA-lcSSc and similar to ATA-dcSSc, although with less frequent restrictive lung disease. The risk of FVC decline ≥10% (35% of ATA-lcSSc) was lower in ATA-lcSSc than in ATA-dcSSc, whereas FVC decline ≥5% occurs similarly between ATA-lcSSc (58% of patients) and other SSc subsets, including ATA-dcSSc. The risk of PMI was similar in ATA-lcSSc and ANA-lcSSc but lower than in ACA-lcSSc; no difference in PH and mortality risk was observed among lcSSc subsets. The risk of any organ involvement, PMI and PH was lower and the mortality tended to be lower in ATA-lcSSc vs ATA-dcSSc. CONCLUSION: ATA-lcSSc patients have a high risk of ILD, albeit with a lower risk of progression compared with ATA-dcSSc, supporting careful screening for ILD in this subgroup

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

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. CONCLUSIONS: HAQ-DI score and major advanced organ involvement were comparable predictors of mortality risk in dcSSc. Baseline mRSS and baseline HAQ-DI score were predictive of HAQ-DI score progression at 1 year, indicating a correlation between these endpoints in monitoring disease progression. It is hoped that this EUSTAR analysis may change physician perception about the importance of the HAQ-DI score in dcSSc

A comparison between nailfold capillaroscopy patterns in adulthood in juvenile and adult-onset systemic sclerosis: a EUSTAR exploratory study

Objective: Qualitative capillaroscopy patterns in juvenile- and adult-onset systemic sclerosis (SSc) were studied in adulthood using data from the EULAR Scleroderma Trials and Research (EUSTAR) database. Methods: Data collected between June 2004 and April 2013 were examined with focus on capillaroscopy. In this retrospective exploratory study, series of patients with juvenile-onset SSc were matched with series of adult-onset SSc having the same gender and autoantibody profile. Results: 30 of 123 patientswith juvenile-onset and 2108 of 7133with adult-onset SSc had data on capillaroscopy. Juvenile-onset SSc showed scleroderma pattern more frequently than adult-onset SSc (93.3% and 88%). The OR was 2.44 and 95% CI 0.57–10.41. An active scleroderma pattern was present in 58% of juvenile- and 61% of adult-onset SSc. The OR was 0.91 and 95% CI 0.28–2.93. The late scleroderma pattern was present in 61% of juvenile- and 55.5% of adult-onset SSc. The OR was 1.06 and 95% CI 0.34–3.56. Conclusion: This is the first exploratory study on the comparison of capillaroscopy between juvenile- and adult-onset SSc in adulthood. Juvenile-onset SSc had an increase prevalence of scleroderma pattern, but a similar distribution of the three patterns was suggested. Further studies are needed to define this issue. © 2015 Elsevier Inc. All rights reserved