Effect of Nintedanib on Progression of Systemic Sclerosis-Associated Interstitial Lung Disease Over 100 Weeks: Data From a Randomized Controlled Trial.

Objective: In the SENSCIS trial, participants with systemic sclerosis-associated interstitial lung disease (SSc-ILD) were randomized to receive nintedanib or placebo until the last participant reached week 52 but for 100 weeks or less. Nintedanib reduced the rate of decline in forced vital capacity (FVC) (ml/year) over 52 weeks by 44% (41 ml [95% confidence interval (95% CI): 2.9-79.

Decline in forced vital capacity in subjects with systemic sclerosis-associated interstitial lung disease in the SENSCIS trial compared with healthy reference subjects.

Background: The forced vital capacity (FVC) of healthy individuals depends on their age, sex, ethnicity and height. Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is characterised by loss of FVC. We compared FVC values in the subjects with SSc-ILD in the SENSCIS trial of nintedanib versus placebo with values from hypothetical matched healthy references.

A phase 2 randomized, double-blinded, placebo-controlled, multicenter trial evaluating the efficacy and safety of raloxifene for patients with mild to moderate COVID-19.

Background: Current available therapeutic options for Coronavirus Disease-2019 (COVID-19) are primarily focused on treating hospitalized patients, and there is a lack of oral therapeutic options to treat mild to moderate outpatient COVID-19 and prevent clinical progression. Raloxifene was found as a promising molecule to treat COVID-19 due to its activity to modulate the replication of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and act as an immunomodulator to decrease proinflammatory cytokines.

Methods: This was a phase 2 multicenter, randomized, placebo-controlled trial to evaluate the efficacy and safety of raloxifene in adult patients with mild to moderate COVID-19 between October 2020 to June 2021 in five centers located in Italy.

Translational engagement of lysophosphatidic acid receptor 1 in skin fibrosis: from dermal fibroblasts of patients with scleroderma to tight skin 1 mouse.

Background And Purpose: Genetic deletion and pharmacological studies suggest a role for lysophosphatidic acid (LPA ) receptor in fibrosis. We investigated the therapeutic potential in systemic sclerosis (SSc) of a new orally active selective LPA receptor antagonist using dermal fibroblasts from patients and an animal model of skin fibrosis.

Experimental Approach: Dermal fibroblast and skin biopsies from systemic sclerosis patients were used.

T-Cell Proapoptotic and Antifibrotic Activity Against Autologous Skin Fibroblasts Is Associated With IL-17A Axis Upregulation in Systemic Sclerosis.

Systemic sclerosis (SSc) T cells can induce apoptosis of autologous skin fibroblasts . Th17 cells have been reported to increase in SSc patients, and interleukin-17A (IL-17A) has a profibrotic function. We used a system based on T-cell-autologous fibroblast co-cultures to further investigate a possible role of IL-17A in SSc.

Prediction of organ involvement and survival in systemic sclerosis patients in the first 5 years from diagnosis.

Background: Organ involvement often occurs in early systemic sclerosis and has been related to premature death. Identifying patients at diagnosis at risk of developing early organ involvement would be useful to optimize screening and management strategies.

Objective: To develop prediction models for the 5-year development of interstitial lung disease, pulmonary arterial hypertension and death.

Outcomes of limited cutaneous systemic sclerosis patients: Results on more than 12,000 patients from the EUSTAR database.

Objectives: Limited cutaneous systemic sclerosis (LcSSc) is the most common subset of SSc but it has been overlooked in the past years. At a time at which clinical trials focus on diffuse cutaneous SSc (DcSSc) we aimed at clarifying the outcomes of LcSSc and at evaluating whether potential drug positioned in DcSSc may also be used in LcSSc.

Methods: The EUSTAR database was used to investigate skin, lung and peripheral vasculopathy outcomes in LcSSc.

Incidence and risk factors for gangrene in patients with systemic sclerosis from the EUSTAR cohort.

Objective: In patients with SSc, peripheral vasculopathy can promote critical ischaemia and gangrene. The aim of this study was to investigate the prevalence, incidence and risk factors for gangrene in the EUSTAR cohort.

Methods: We included patients from the EUSTAR database fulfilling the ACR 1980 or the ACR/EULAR 2013 classification criteria for SSc, with at least one visit recording data on gangrene.

Performance of a new quantitative computed tomography index for interstitial lung disease assessment in systemic sclerosis.

Quantitative high resolution computed tomography (HRCT) may objectively assess systemic sclerosis (SSc)-interstitial lung disease (ILD) extent, using three basic densitometric measures: mean lung attenuation (MLA), skewness, and kurtosis. This prospective study aimed to develop a composite index - computerized integrated index (CII) - that accounted for MLA, skewness, and kurtosis by means of Principal Component Analysis over HRCTs of 83 consecutive SSc subjects, thus eliminating redundancies. Correlations among CII, cardiopulmonary function and immune-inflammatory biomarkers (e.

Phenotypes Determined by Cluster Analysis and Their Survival in the Prospective European Scleroderma Trials and Research Cohort of Patients With Systemic Sclerosis.

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.

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

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.

Anti-carbamylated protein antibodies and skin involvement in patients with systemic sclerosis: An intriguing association.

Carbamylation is a post-translational modification that mostly affects proteins with low turnover, such as dermal proteins. Carbamylated proteins accumulate in skin in an age-dependent manner, contributing to tissue alterations. As dermis is affected by systemic sclerosis (SSc) and anti-carbamylated protein antibodies (anti-CarP Ab) are found in SSc patients, we sought to evaluate the specificity of anti-CarP Ab and their relationship with clinical parameters reflecting skin involvement in SSc.

Hemodynamic changes after acute fluid loading in patients with systemic sclerosis without pulmonary hypertension.

A fluid challenge with a rapid infusion of saline helps to discriminate between pre- and post-capillary pulmonary hypertension (PH) and allows unmasking hidden post-capillary PH. Systemic sclerosis (SSc) patients may present with biventricular systolic and diastolic dysfunction. The aim of this study was to evaluate the hemodynamic changes of the pulmonary circulation in SSc patients without PH after a fluid challenge.

Guidelines for biomarkers in autoimmune rheumatic diseases - evidence based analysis.

Autoimmune rheumatic diseases are characterised by an abnormal immune system response, complement activation, cytokines dysregulation and inflammation. In last years, despite many progresses in managing these patients, it has been shown that clinical remission is reached in less than 50% of patients and a personalised and tailored therapeutic approach is still lacking resulting in a significant gap between guidelines and real-world practice. In this context, the need for biomarkers facilitating early diagnosis and profiling those individuals at the highest risk for a poor outcome has become of crucial interest.

Gender differences in early systemic sclerosis patients: a report from the EULAR scleroderma trials and research group (EUSTAR) database.

Objectives: To describe differences in clinical presentation between men and women in a large group of patients with early (<3 years' duration) systemic sclerosis (SSc) according to disease subsets.

Methods: A cross-sectional analysis of the prospective EULAR Scleroderma Trial and Research database (EUSTAR) was performed. Patients fulfilling preliminary ACR 1980 classification criteria for SSc, with less than 3 years from the first non-Raynaud's symptom at first entry, were selected.

Esophageal high-resolution impedance manometry alterations in asymptomatic patients with systemic sclerosis: prevalence, associations with disease features, and prognostic value.

This study aims to investigate pre-clinical esophageal involvement in systemic sclerosis (SSc) by high-resolution impedance manometry (HRiM), its associations with disease features including lung involvement, and its predictivity of esophageal symptoms overtime. Charts of 45 asymptomatic (no heartburn/regurgitation/dysphagia) SSc patients (96% females; mean age 46 years) with at least one follow-up (FU) visit and complete clinical, serological, functional, and radiological assessment, including high-resolution computed tomography (HRCT) of the chest and lung function tests, that had undergone esophageal HRiM were retrospectively evaluated. Esophagogastric junction-contractile integral (EGJ-CI) and esophageal body motility, as evaluated by mean distal contractile integral (DCI), were assessed.

Mapping and predicting mortality from systemic sclerosis.

Objectives: To determine the causes of death and risk factors in systemic sclerosis (SSc).

Methods: Between 2000 and 2011, we examined the death certificates of all French patients with SSc to determine causes of death. Then we examined causes of death and developed a score associated with all-cause mortality from the international European Scleroderma Trials and Research (EUSTAR) database.

International consensus: What else can we do to improve diagnosis and therapeutic strategies in patients affected by autoimmune rheumatic diseases (rheumatoid arthritis, spondyloarthritides, systemic sclerosis, systemic lupus erythematosus, antiphospholipid syndrome and Sjogren's syndrome)?: The unmet needs and the clinical grey zone in autoimmune disease management.

Autoimmune diseases are a complex set of diseases characterized by immune system activation and, although many progresses have been done in the last 15years, several unmet needs in the management of these patients may be still identified. Recently, a panel of international Experts, divided in different working groups according to their clinical and scientific expertise, were asked to identify, debate and formulate a list of key unmet needs within the field of rheumatology, serving as a roadmap for research as well as support for clinicians. After a systematic review of the literature, the results and the discussions from each working group were summarised in different statements.

Clinical determinants of elevated systolic pulmonary artery pressure measured by transthoracic Doppler echocardiography in early systemic sclerosis.

Objectives: To explore the prevalence and clinical associations of elevated systolic pulmonary artery pressure (sPAP), measured by Transthoracic Doppler-echocardiography (TTE) in patients with early systemic sclerosis (SSc).

Methods: A cross-sectional analysis of the prospective EULAR Scleroderma Trial and Research (EUSTAR) database was performed. SSc patients with <3 years from the first non-Raynaud's phenomenon (RP) symptom at baseline EUSTAR visit, were selected.

The cumulative number of micro-haemorrhages and micro-thromboses in nailfold videocapillaroscopy is a good indicator of disease activity in systemic sclerosis: a validation study of the NEMO score.

Background: Some abnormalities in nailfold videocapillaroscopy (NVC), such as the presence of micro-haemorrhages (MHEs), micro-thromboses (MTs), giant capillaries (GCs) and reduction in the number of capillaries (nCs), suggest a disease activity (DA) phase in systemic sclerosis (SSc). In a previous paper, we showed that the number of micro-haemorrhages and micro-thromboses (the so-called NEMO score) was the NVC feature more closely associated with DA. The present study was aimed at validating the NEMO score as a measure of DA in patients with SSc.

Functional disability and its predictors in systemic sclerosis: a study from the DeSScipher project within the EUSTAR group.

Objectives: The multisystem manifestations of SSc can greatly impact patients' quality of life. The aim of this study was to identify factors associated with disability in SSc.

Methods: SSc patients from the prospective DeSScipher cohort who had completed the scleroderma health assessment questionnaire (SHAQ), a disability score that combines the health assessment questionnaire and five visual analogue scales, were included in this analysis.