scholarly journals Correction: Development and validation of the Scleroderma Clinical Trials Consortium Damage Index (SCTC-DI): a novel instrument to quantify organ damage in systemic sclerosis

2019 ◽  
Vol 78 (8) ◽  
pp. e88-e88
Keyword(s):  
Clinical Trials ◽  
Systemic Sclerosis ◽  
Damage Index ◽  
Organ Damage ◽  
Development And Validation

scholarly journals Development and validation of the Scleroderma Clinical Trials Consortium Damage Index (SCTC-DI): a novel instrument to quantify organ damage in systemic sclerosis

2019 ◽  
Vol 78 (6) ◽  
pp. 807-816 ◽  
Author(s):  
Nava Ferdowsi ◽  
Molla Huq ◽  
Wendy Stevens ◽  
Marie Hudson ◽  
Mianbo Wang ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Systemic Sclerosis ◽  
Short Form ◽  
Damage Index ◽  
Clinical Importance ◽  
Organ Damage ◽  
Physical Component Summary Score ◽  
Summary Score ◽  
Data Set ◽  
Mortality And Morbidity

ObjectiveWe sought to develop the first Damage Index (DI) in systemic sclerosis (SSc).MethodsThe conceptual definition of ‘damage’ in SSc was determined through consensus by a working group of the Scleroderma Clinical Trials Consortium (SCTC). Systematic literature review and consultation with patient partners and non-rheumatologist experts produced a list of potential items for inclusion in the DI. These steps were used to reduce the items: (1) Expert members of the SCTC (n=331) were invited to rate the appropriateness of each item for inclusion, using a web-based survey. Items with >60% consensus were retained; (2) Using a prospectively acquired Australian cohort data set of 1568 patients, the univariable relationships between the remaining items and the endpoints of mortality and morbidity (Physical Component Summary score of the Short Form 36) were analysed, and items with p<0.10 were retained; (3) using multivariable regression analysis, coefficients were used to determine a weighted score for each item. The DI was externally validated in a Canadian cohort.ResultsNinety-three (28.1%) complete survey responses were analysed; 58 of 83 items were retained. The univariable relationships with death and/or morbidity endpoints were statistically significant for 22 items, with one additional item forced into the multivariable model by experts due to clinical importance, to create a 23-item weighted SCTC DI (SCTC-DI). The SCTC-DI was predictive of morbidity and mortality in the external cohort.ConclusionsThrough the combined use of consensus and data-driven methods, a 23-item SCTC-DI was developed and retrospectively validated.

scholarly journals OP0273 THE SCLERODERMA CLINICAL TRIALS CONSORTIUM DAMAGE INDEX (SCTC-DI) IN A SYSTEMIC SCLEROSIS COHORT WITH 10-YEARS FOLLOW-UP

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 166.2-166
Author(s):  
M. G. Lazzaroni ◽  
M. Breda ◽  
F. Franceschini ◽  
P. Airò
Keyword(s):  
Clinical Trials ◽  
Systemic Sclerosis ◽  
Multivariable Analysis ◽  
Damage Index ◽  
Organ Damage ◽  
Severe Damage ◽  
Time Points ◽  
Cutaneous Involvement ◽  
Male Sex

Background:Systemic Sclerosis (SSc) is characterized by increased mortality and organ damage accrual. A composite SSc Damage Index was recently developed by the Scleroderma Clinical Trials Consortium (SCTC-DI) and was demonstrated as a predictor of mortality both in the Australian derivation cohort and in the Canadian validation cohort.Objectives:To evaluate in a single centre cohort of SSc patients with 10-years follow-up: (1) the evolution of organ damage over time; (2) factors associated with the development and accrual of organ damage.Methods:A retrospective analysis was performed on patients prospectively followed in our centre from 1989 to 2019. Organ damage was evaluated with SCTC-DI (0-55 scale; moderate damage >5, severe damage>12) and comorbidities with Charlson Comorbidity Index (CCI, which includes the age of the patient). Patients were included when a follow-up of at least 10 years was available together with SCTC-DI at the diagnosis (baseline, T0), 1 year (T1), 5 years (T5) and 10 years (T10) after the diagnosis. Univariable and multivariable analysis (logistic regression) were performed when appropriated.Results:253 SSc patients were included (female 93%; Caucasians: 99%; median age at diagnosis: 52 years (IQR: 43-60); diffuse cutaneous subset: 15%; anti-centromere (ACA)+ 55%; anti-Topoisomerase 1 + 20%; anti-RNA polymerase III+: 4%; ever smokers: 28%). Median interval between the first SSc symptom other than Raynaud’s phenomenon and the diagnosis was 1 year. SCTC-DI progressively increased from diagnosis to T10 (p<0.0001; Kruskal-Wallis test).Moderate damage (score:6-12) was observed in 22 patients at T0 (8.7%), in 30 at T1 (11.9%), in 45 at T5 (17.7%) and in 73 at T10 (28.9%). None of the patients had severe damage (score:13-55) at T0 and T1, while it was present in 6 at T5 (2.4%) and in 13 at T10 (5.1%).At T0 no difference in SCTC-DI scores was observed when comparing different subgroups according to gender (female vs. male), disease subsets (diffuse vs. limited) and autoantibodies (ACA- vs. ACA+). At T1, SCTC-DI score was higher in patients with diffuse vs. limited cutaneous subset, and ACA- vs ACA+ (p<0.0001 for both).Multivariable analysis demonstrated that a moderate or severe organ damage (SCTC-DI score >5) at 5 years was positively associated with diffuse cutaneous involvement (p:0.009, OR 4.55, 1.46-14.1), SCTC-DI at T0 (p:0.015, OR 1.34, 1.06-1.70) and at T1 (p:<0.0001, OR 1.65, 1.30-2.07), and negatively associated with ACA+ (p:0.024, OR 0.32, 0.12-0.86), while CCI and male sex showed no association. At 10 years SCTC-DI>5 was associated with diffuse cutaneous involvement (p:0.013, OR 4.30, 1.36-13.7), SCTC-DI at T5 (p:<0.0001, OR 1.67, 1.38-2.01), while SCTC-DI at T0, CCI, male sex and ACA+ had no association.Among 253 patients, 90 (36%) died after >10 years of follow-up. In non-survivors, as compared to survivors, SCTC-DI score was significantly higher at the baseline (T0) and during the entire follow-up (p<0.0001 for every timepoint).Conclusion:At the end of 10-years follow-up (T10), 35% of patients in our cohort had moderate or severe organ damage (SCTC-DI score>5). Diffuse cutaneous involvement was associated with higher SCTC-DI scores at different time points (T5 and T10). Organ damage, quantified by SCTC-DI at different time points, was confirmed as a factor associated with mortality in patients who reached more than 10 years of follow-up.References:[1]Ferdowsi N, et al. Ann Rheum Dis. 2019;78:807-16.Disclosure of Interests:None declared

scholarly journals Systemic Sclerosis Pathogenesis and Emerging Therapies, beyond the Fibroblast

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Andrea Sierra-Sepúlveda ◽  
Alexia Esquinca-González ◽  
Sergio A. Benavides-Suárez ◽  
Diego E. Sordo-Lima ◽  
Adrián E. Caballero-Islas ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Immune System ◽  
Systemic Sclerosis ◽  
Autoimmune Disease ◽  
State Of The Art ◽  
Therapeutic Targets ◽  
Organ Damage ◽  
The State ◽  
Pathogenic Mechanism ◽  
Emerging Therapies

Systemic sclerosis (SSc) is a complex rheumatologic autoimmune disease in which inflammation, fibrosis, and vasculopathy share several pathogenic pathways that lead to skin and internal organ damage. Recent findings regarding the participation and interaction of the innate and acquired immune system have led to a better understanding of the pathogenesis of the disease and to the identification of new therapeutic targets, many of which have been tested in preclinical and clinical trials with varying results. In this manuscript, we review the state of the art of the pathogenesis of this disease and discuss the main therapeutic targets related to each pathogenic mechanism that have been discovered so far.

scholarly journals Predictors of disease worsening defined by progression of organ damage in diffuse systemic sclerosis: a European Scleroderma Trials and Research (EUSTAR) analysis

2019 ◽  
Vol 78 (9) ◽  
pp. 1242-1248 ◽  
Author(s):  
Mike Becker ◽  
Nicole Graf ◽  
Rafael Sauter ◽  
Yannick Allanore ◽  
John Curram ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Systemic Sclerosis ◽  
Disease Progression ◽  
Muscle Weakness ◽  
Lung Fibrosis ◽  
Heart Function ◽  
Strong Association ◽  
Organ Damage ◽  
Inclusion Criteria ◽  
Patients At Risk

ObjectivesMortality 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.MethodsInclusion 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.ResultsOf 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.ConclusionsThe use of the predictive factors presented here could enable cohort enrichment with patients at risk for overall disease worsening in SSc clinical trials.

Early Accrual of Organ Damage in Systemic Sclerosis: Rationale for Development of a Disease Damage Index

2017 ◽  
Vol 2 (2) ◽  
pp. 127-134 ◽  
Author(s):  
Tien Tay ◽  
Molla Huq ◽  
Nava Ferdowsi ◽  
Wendy Stevens ◽  
Joanne Sahhar ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Damage Index ◽  
Organ Damage ◽  
Disease Damage

scholarly journals POS0324 SMOKING HISTORY AND SCLERODERMA CLINICAL TRIALS CONSORTIUM DAMAGE INDEX (SCTC-DI) AS INDEPENDENT PREDICTORS OF MORTALITY IN SYSTEMIC SCLEROSIS IN A SINGLE-CENTRE ITALIAN COHORT

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 389.1-389
Author(s):  
M. Breda ◽  
M. G. Lazzaroni ◽  
F. Franceschini ◽  
P. Airò
Keyword(s):  
Clinical Trials ◽  
Cox Regression ◽  
Damage Index ◽  
Organ Damage ◽  
Smoking History ◽  
Single Centre ◽  
Cox Regression Analysis ◽  
Predictors Of Mortality ◽  
Italian Cohort

Background:Systemic Sclerosis (SSc) is characterized by increased mortality and organ damage accrual. A composite SSc Damage Index was recently developed by the Scleroderma Clinical Trials Consortium (SCTC-DI) and was demonstrated as a predictor of mortality both in the Australian derivation cohort and in the Canadian validation cohort (1). Several independent predictors of mortality in SSc have been reported, but only limited data are available on the role of smoking.Objectives:To evaluate smoking history and SCTC-DI as independent predictors of mortality in SSc in a single centre Italian cohort.Methods:A retrospective analysis was performed on patients prospectively followed in our centre from 1989 to 2019, with at least 2 evaluations and/or cause of death available. Organ damage was evaluated through the SCTC-DI (0-55 scale; severe damage>12), while comorbidities through the Charlson Comorbidity Index (CCI). Survival analysis was performed with Kaplan-Meier curves and with Log-rank test to compare different subsets. Cox-regression analysis was performed to identify baseline independent predictors of mortality.Results:648 SSc patients were 99% Caucasian, 90% female and had a median age at diagnosis of 55.5 years (IQR: 45.0-65.6); 19% had diffuse cutaneous involvement. ACA was positive in 52%; anti-TopoI in 22% and anti-RNA Polymerase III in 5%.Median SCTC-DI at diagnosis was 2 (0-4) (n=560); ever smokers were 27%. During the follow-up 240 patients died after a median period of 10.2 years (4.9-16.8). The cause of death was related to SSc in 41% (n=65; most frequent causes pulmonary arterial hypertension (n=35) and interstitial lung disease (n=30)) and to other diseases in 40% (n=95; most frequent cause cancer (n=40)), while was indeterminate in 19%.Overall survival at 5, 10, 15, 20 years was 87.8% (SE 1.3%), 75.6% (1.9), 63.8% (2.3), 47.7% (2.8), respectively and was higher in females vs. males (p<0.0001) and in ACA+ vs ACA- (p=0.005), but did not differ between cutaneous subsets. 111 patients were lost at follow-up (17%).In the Cox-regression analysis smoking history and severe organ damage at diagnosis (score>12) were identified as independent predictors of death, while age at diagnosis, female gender, diffuse cutaneous subsets, ACA positivity and CCI were not (Table 1).Conclusion:Smoking history and severe organ damage were independent predictors of death in a large Italian single centre SSc cohort. SCTC-DI was confirmed as a useful tool to predict mortality at every timepointReferences:[1]Ferdowsi N, et al. Ann Rheum Dis. 2019;78:807-16.Disclosure of Interests:None declared

scholarly journals FRI0226 OPTICAL COHERENCE TOMOGRAPHY OF THE SKIN DETECTS SCLERODERMA CHANGES IN CLINICALLY UNAFFECTED SKIN: AN OPPORTUNITY FOR EARLY DETECTION OF SYSTEMIC SCLEROSIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 696.2-696
Author(s):  
G. Abignano ◽  
D. Temiz Karadağ ◽  
O. Gundogdu ◽  
G. Lettieri ◽  
M. C. Padula ◽  
...  
Keyword(s):  
At Risk ◽  
Clinical Trials ◽  
Optical Coherence Tomography ◽  
Systemic Sclerosis ◽  
Early Detection ◽  
Classification Criteria ◽  
Healthy Controls ◽  
Optical Coherence ◽  
Risk Patients ◽  
Unaffected Skin

Background:The Very Early Diagnosis Of Systemic Sclerosis (VEDOSS) study has shown that 82% of patients with Raynaud’s Phenomenon, specific ANA positivity and scleroderma pattern at nail fold videocapillaroscopy will fulfil classification criteria within 5 years. This is suggesting that there is a subclinical window of opportunity to diagnose systemic sclerosis (SSc) before clinical manifestations occur. In this scenario, a non-invasive tool to diagnose SSc in clinically unaffected skin might improve the early detection of disease in at risk-patients. Optical coherence tomography (OCT) of the skin has been shown to be a sensitive and accurate biomarker of skin fibrosis in SSc.Objectives:Here we aimed to assess the ability of skin OCT to “detect” SSc in clinically unaffected skin from a multicentre cohort.Methods:Dorsal forearm skin of SSc patients and matched-healthy controls (HC) was evaluated using VivoSight scanner (Michelson Diagnostics). Mean A-scans (mean OCT signal plotted against depth-in-tissue) were derived as previously described. Minimum Optical Density (MinOD), Maximum OD (MaxOD) and OD at 300 micron-depth (OD300) were calculated. Clinical involvement was assessed by an operator blinded to OCT findings using the mRSS. Receiver-operating characteristic (ROC) curve analysis was carried out for MinOD, MaxOD, and OD300 to evaluate their ability to discriminate between SSc and HC. Statistical analysis was performed using GraphPad Prism software V.7.0.Results:One hundred seventy four OCT images were collected from 87 subjects [43 SSc (39 Female, mean age 49.7±9.1 years) and 44 gender/age-matched healthy controls (HC) (36 Female, mean age 50.2±8.3 years)] in two different SSc centres. All patients fulfilled classification criteria for SSc. OCT measures demonstrated discriminative ability in SSc skin detection with any clinical skin involvement (0-3 at site of analysis) with an AUC of 0.73 (MinOD, 95%CI 0.64-0.81), 0.77 (MaxOD, 95%CI 0.7-0.85) and 0.82 (OD300, 95%CI 0.76-0.89); p<0.0001 for all as previously indicated. Most importantly, all three measures showed comparable performance in detecting scleroderma also in clinically unaffected skin (mRss=0 at site of analysis), with an AUC of 0.7 (95%CI 0.6-0.81, p=0.001), 0.72 (95%CI 0.61-0.83, p=0.0003) and 0.72 (95%CI 0.61-0.83, p=0.0003) for MinOD, MaxOD and OD300 respectively.Conclusion:Virtual biopsy by OCT recognises clinically unaffected skin of SSc patients from the HC skin. This is consistent with gene array data showing that scleroderma specific signatures are consistent in affected and clinically unaffected skin. These results inform future studies on at risk patients with clinically unaffected skin which may define a role for OCT in detecting subclinical SSc.Disclosure of Interests:Giuseppina Abignano: None declared, Duygu Temiz Karadağ: None declared, Ozcan Gundogdu: None declared, Giovanni Lettieri: None declared, Maria Carmela Padula: None declared, Angela Padula: None declared, Paul Emery Grant/research support from: AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche (all paid to employer), Consultant of: AbbVie (consultant, clinical trials, advisor), Bristol-Myers Squibb (consultant, clinical trials, advisor), Lilly (clinical trials, advisor), Merck Sharp & Dohme (consultant, clinical trials, advisor), Novartis (consultant, clinical trials, advisor), Pfizer (consultant, clinical trials, advisor), Roche (consultant, clinical trials, advisor), Samsung (clinical trials, advisor), Sandoz (clinical trials, advisor), UCB (consultant, clinical trials, advisor), Salvatore D’Angelo: None declared, Francesco Del Galdo: None declared

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