34 research outputs found
The effect of hydroxychloroquine on activities of daily living and hand function in systemic sclerosis: results from an analysis of the EUSTAR cohort
No full textBackground: To evaluate the use of hydroxychloroquine (HCQ) and its impact on the Health Assessment Questionnaire disability index(HAQ-DI) and the Cochin Hand Function Status(CHFS) in a large Systemic Sclerosis (SSc) cohort. Methods: SSc patients from the European Scleroderma Trials and Research (EUSTAR) database treated with HCQ for at least 6 months were evaluated and compared to a matched group of SSc patients not using HCQ. Demographic and clinical data, concomitant drugs, HAQ-DI and CHFS (at least 2 evaluations) were recorded and were the outcome variables of interest. Statistical analysis was performed using propensity score matching for age, gender, disease duration, corticosteroids, immunosuppressives, vasoactive drugs in a 3:1 control: HCQ ratio. Standard descriptive statistics and Student’s t-test and Chi-square test were used to assess the propensity-matched groups. Results: Out of 17,805 SSc patients evaluated, 468 (2.6%) used HCQ and constituted the HCQ group. Among them, 50 (10.7%) had at least a baseline and follow-up HAQ-DI evaluation and 44 (9.4%) had at least a baseline and follow-up CHFS evaluation. Propensity matching assured that patients were matched for female gender (HCQ vs. control 92.0% vs. 85.3%), mean age (49.8 vs. 50.0 years) disease duration (8.3 vs. 9.1 years), limited disease (55.3 vs. 62.6%) as well as background medications (all P > 0.1). We did not find any significant differences among the two groups in the change of HAQ-DI or CHFS, over up to 365 days (all P > 0.05). Conclusions: Results from the EUSTAR registry showed that HCQ was used by 2.6% of SSc patients. HCQ use did not improve the HAQ-DI, or CHFS when comparing HCQ users to non-HCQ users
Brief Report: Smoking in Systemic Sclerosis: A Longitudinal European Scleroderma Trials and Research Group Study
No full textObjective: 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 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
Progressive interstitial lung disease in patients with systemic sclerosis-associated interstitial lung disease in the EUSTAR database
No full textObjectives To identify overall disease course, progression patterns and risk factors predictive for progressive interstitial lung disease (ILD) in patients with systemic sclerosis-associated ILD (SSc-ILD), using data from the European Scleroderma Trials And Research (EUSTAR) database over long-term follow-up. Methods Eligible patients with SSc-ILD were registered in the EUSTAR database and had measurements of forced vital capacity (FVC) at baseline and after 12±3 months. Long-term progressive ILD and progression patterns were assessed in patients with multiple FVC measurements. Potential predictors of ILD progression were analysed using multivariable mixed-effect models. Results 826 patients with SSc-ILD were included. Over 12±3 months, 219 (27%) showed progressive ILD: either moderate (FVC decline 5% to 10%) or significant (FVC decline >10%). A total of 535 (65%) patients had multiple FVC measurements available over mean 5-year follow-up. In each 12-month period, 23% to 27% of SSc-ILD patients showed progressive ILD, but only a minority of patients showed progression in consecutive periods. Most patients with progressive ILD (58%) had a pattern of slow lung function decline, with more periods of stability/improvement than decline, whereas only 8% showed rapid, continuously declining FVC; 178 (33%) experienced no episode of FVC decline. The strongest predictive factors for FVC decline over 5 years were male sex, higher modified Rodnan skin score and reflux/dysphagia symptoms. Conclusion SSc-ILD shows a heterogeneous and variable disease course, and thus monitoring all patients closely is important. Novel treatment concepts, with treatment initiation before FVC decline occurs, should aim for prevention of progression to avoid irreversible organ damage
Glucocorticoids prescribing practices in systemic sclerosis: an analysis of the EUSTAR database
No full textTo estimate the long-term exposure to glucocorticoids (GC), the factors associated with, and the variations in prescribing practices over time and across recruiting countries
Effectiveness and safety of tocilizumab in patients with systemic sclerosis: a propensity score matched controlled observational study of the EUSTAR cohort
No full textObjectives Tocilizumab showed trends for improving skin fibrosis and prevented progression of lung fibrosis in systemic sclerosis (SSc) in randomised controlled clinical trials. We aimed to assess safety and effectiveness of tocilizumab in a real-life setting using the European Scleroderma Trial and Research (EUSTAR) database. Methods Patients with SSc fulfilling the American College of Rheumatology (ACR)/EULAR 2013 classification criteria, with baseline and follow-up visits at 12±3 months, receiving tocilizumab or standard of care as the control group, were selected. Propensity score matching was applied. Primary endpoints were the modified Rodnan skin score (mRSS) and FVC at 12±3 months compared between the groups. Secondary endpoints were the percentage of progressive/regressive patients for skin and lung at 12±3 months. Results Ninety-three patients with SSc treated with tocilizumab and 3180 patients with SSc with standard of care fulfilled the inclusion criteria. Comparison between groups did not show significant differences, but favoured tocilizumab across all predefined primary and secondary endpoints: mRSS was lower in the tocilizumab group (difference -1.0, 95% CI -3.7 to 1.8, p=0.48). Similarly, FVC % predicted was higher in the tocilizumab group (difference 1.5 (-6.1 to 9.1), p=0.70). The percentage of progressive/regressive patients favoured tocilizumab over controls. These results were robust regarding the sensitivity analyses. Safety analysis confirmed previously reported adverse event profiles. Conclusion Although this large, observational, controlled, real-life EUSTAR study did not show significant effectiveness of tocilizumab on skin and lung fibrosis, the consistency of direction of all predefined endpoints generates hypothesis for potential effectiveness in a broader SSc population
Translational research in rheumatoid arthritis: Exploiting melanocortin receptors
No full textThe copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the authorRheumatoid arthritis (RA) is a chronic inflammatory disease affecting 1% of the population. The aetiology of rheumatoid arthritis is unknown, although there are multiple postulated theories. In 1950, Philip Hench won the Nobel prize for treating patients with rheumatoid arthritis with cortisone. He also treated 6 patients with adrenocorticotropic hormone (ACTH) with good results. ACTH is a melanocortin. The melanocortin system describes the five melanocortin receptors, their ligands, agonists and antagonists and the accessory proteins. The aim of this study was to explore the melanocortin receptors in rheumatoid arthritis synovium.
Methods
HA-tagged stable cell lines were created for MC1R, MC3R and MC5R. Multiple antibodies were tested for their utility using Western Blot, immunohistochemistry and flow cytometry. Samples of synovium from 28 patients with RA were tested using RTPCR for the presence of MC1R and MC3R. Gene expression was correlated with clinical characteristics, cytokine (RTPCR) expression and immunohistochemical score.
Results
The stable cell lines expressed MC1R, MC3R and MC5R respectively. Of the antibodies tested none were found to be of utility in detecting MC1R or MC3R .The MC1R RQ values in rheumatoid synovium appear to split into two groups, high and low. The medians of the two groups are significantly different (p=0.0005). There is almost a 5 cycle, or 64 fold, difference in gene expression between the medians of the two groups (1.59 v 6.23). Of note no MC3R positive samples were CD138 high (i.e. no MC3R positive samples had a significant plasma cell infiltrate) (p=0.006). Categorical analysis using Fishers Exact test revealed an association between MC1R high samples and CD68 lining high scores, (i.e. MC1R high samples also had a high macrophage score in the lining of the sample) (p=0.02). MC1R low samples were associated with not being on combination therapy,
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this did not quite reach significance (p=0.07). Linear regression analysis confirmed these associations for MC1R. PCA analysis did not show any grouping of samples according to any of the variables tested, likely due to sample size.
Conclusion
MC1R and MC3R are found in human synovium. Current commercial antibodies are not of utility in detecting MC1R or MC3R. Synovial samples can be split into high and low MC1R gene expression groups. MC3R was either present or absent. High expression of MC1R was associated with a high macrophage score and MC3R expression was associated with a low plasma cell score. MC1R and MC3R expression in RA synovium could be used as biomarkers of disease state or severity as well as a target for therapy
Deep hierarchical subtyping of multi-organ systemic sclerosis trajectories - a EUSTAR study
No full textSystemic sclerosis (SSc) is a chronic autoimmune disease with multi-organ involvement. Historically, SSc classification has focused on the type of skin involvement (limited versus diffuse); however, a growing evidence of organ-specific variability suggests the presence of more than two distinct subtypes. We propose a semi-supervised generative deep learning framework leveraging expert-driven definitions of organ-specific involvement and severity. We model SSc disease trajectories in the European Scleroderma Trials and Research (EUSTAR) database, containing 14,000 patients across 67,000 medical visits, and identify clinically meaningful subtypes to enhance patient stratification and prognosis. We systematically evaluate the model’s predictive accuracy, robustness to missing data, and clinical interpretability. We identified five patient clusters, separating patients based on the degree of organ involvement. Notably, a subset with limited skin involvement still showed high risks of lung and heart complications, underscoring the importance of data-driven methods and multi-organ models to complement established insights from clinical practice
A comparison between nailfold capillaroscopy patterns in adulthood in juvenile and adult-onset systemic sclerosis: A EUSTAR exploratory study
No full textObjective: 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
Does regression of skin thickening predict improvement of internal organ involvement and survival in patients with diffuse cutaneous systemic sclerosis? A EUSTAR analysis
No full textInternational audienc
Sex influence on outcomes of patients with systemic sclerosis-associated interstitial lung disease: an EUSTAR database analysis
No full textObjective: Interstitial lung disease (ILD) is the leading cause of morbidity/mortality in systemic sclerosis (SSc). We aimed to study investigate the impact of sex on SSc-ILD. Methods: EUSTAR SSc patients with radiological-confirmed ILD and available %predicted forced vital capacity(%pFVC) were included. Demographics and disease features were recorded. Change in %pFVC over 12±6 months (cohort 1) was classified into stable (≤4%), mild (5-9%) and large progression (≥10%). In those with 2-year longitudinal %pFVC (cohort 2), %pFVC change at each 12±6 months interval was calculated. Logistic regression analyses (OR and 95%CI) and Cox proportional hazards models adjusted for age and %pFVC were applied. Results: 1136 male and 5253 female SSc-ILD patients were identified. Males were significantly younger, had a shorter disease duration, higher prevalence of CRP elevation, were had frequently a diffuse cutaneous involvement. In cohort 1(1655 females and 390 males), a higher percentage of males had stable ILD (74.4% versus 69.4%, p = 0.056). In multivariable analysis, disease duration and %pFVC(OR 0.99,0.98-0.99; 0.97,0.95-0.99) in males and age, %pFVC and anti-centromere(OR 1.02,1.00-1.04; 0.97,0.96-0.98; 0.39,0.245-0.63) in females were associated with large progression. The 1-year mortality rate was higher in males (5.1% versus 2.5%, p = 0.013). In cohort 2(849 females and 209 males), a higher percentage of females showed periods of large progression (11.7% versus 7.7%, p = 0.023), the percentage of patients with 0, 1 or 2 periods of worsening was not different. The overall death rate was 30.9% for males and 20.4% in females (p < 0.001). At survival analysis, male sex was a predictor of mortality (OR 1.95, 1.66-2.28). Conclusions: Male SSc-ILD patients have a poorer prognosis and sex-specific predictors exist in SSc-ILD
