4.5 Review

State-of-the-art evidence in the treatment of systemic sclerosis

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Article Rheumatology

Outcomes in patients with systemic sclerosis undergoing early vs delayed intervention with potential disease-modifying therapies

Keina Yomono et al.

Summary: This study aimed to investigate the benefits of early therapeutic intervention in patients with early SSc. The results showed that the early intervention group had a lower proportion of stable pulmonary function, a higher reduction in active disease, and significantly lower rates of clinical worsening compared to the delayed intervention group.

RHEUMATOLOGY (2022)

Article Immunology

Immunosuppressive Therapy After Autologous Hematopoietic Stem Cell Transplantation in Systemic Sclerosis Patients-High Efficacy of Rituximab

Michael Gernert et al.

Summary: This study investigated the use of immunosuppressive medication (IS) after autologous hematopoietic stem cell transplantation (aHSCT) in systemic sclerosis (SSc) patients. The results showed that approximately 60% of SSc patients required IS after aHSCT for disease control. Rituximab was found to be an effective treatment option. Long-term data suggested that aHSCT is safe.

FRONTIERS IN IMMUNOLOGY (2022)

Article Pharmacology & Pharmacy

Current advances in the treatment of systemic sclerosis

Heather Bukiri et al.

Summary: Systemic sclerosis is a rare autoimmune disease with unknown cause. The lack of disease modifying therapies has contributed to its high mortality. Recent randomized controlled trials have provided valuable insights into the pathogenesis and potential treatments for systemic sclerosis, leading to the approval of novel therapies for interstitial lung disease associated with systemic sclerosis.

CURRENT OPINION IN PHARMACOLOGY (2022)

Meeting Abstract Rheumatology

PROGRESSIVE INTERSTITIAL LUNG DISEASE IS FREQUENT ALSO IN LATE DISEASE STAGES IN SYSTEMIC SCLEROSIS PATIENTS FROM EUSTAR

A. M. Hoffmann-Vold et al.

ANNALS OF THE RHEUMATIC DISEASES (2022)

Article Rheumatology

Impact of lung function decline on time to hospitalisation events in systemic sclerosis-associated interstitial lung disease (SSc-ILD): a joint model analysis

Michael Kreuter et al.

Summary: This study investigated the relationship between decline in forced vital capacity (FVC) and hospitalisation endpoints in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD). The results showed a significant association between FVC decline and the risk of all-cause and SSc-related hospitalisations or death. Slowing FVC decline may prevent hospitalisations in patients with SSc-ILD. The findings also suggest that FVC decline may serve as a surrogate endpoint for clinically relevant hospitalisation-associated endpoints.

ARTHRITIS RESEARCH & THERAPY (2022)

Article Hematology

Autologous stem cell transplantation for progressive systemic sclerosis: a prospective non-interventional study from the European Society for Blood and Marrow Transplantation Autoimmune Disease Working Party

Joerg Henes et al.

Summary: This study confirms the efficacy and safety of autologous stem cell transplantation in the treatment of severe systemic sclerosis. It also identifies some prognostic factors that can affect treatment outcomes. Careful cardio-pulmonary assessment before transplantation, reduced cyclophosphamide doses, and CD34(+)-cell selection may improve treatment outcomes.

HAEMATOLOGICA (2021)

Review Rheumatology

The effects of oral treatment for systemic sclerosis related pulmonary arterial hypertension: A systematic review and meta-analysis

Yunxia Lei et al.

Summary: Oral therapies have shown benefits for patients with pulmonary arterial hypertension related to systemic sclerosis, and combination therapy may be more effective in improving exercise capacity and hemodynamic parameters.

MODERN RHEUMATOLOGY (2021)

Article Biophysics

Cardiac safe hematopoietic stem cell transplantation for systemic sclerosis with poor cardiac function: a pilot safety study that decreases neutropenic interval to 5 days

Richard K. Burt et al.

Summary: The fludarabine-based regimen was relatively safe with a TRM of 2.4% and a neutropenic interval of only 5.2 days in systemic sclerosis patients with a high-risk cardiac phenotype. The addition of rituximab decreased 1-year relapse rate, risk of late secondary autoimmune diseases, and upper-respiratory tract infections.

BONE MARROW TRANSPLANTATION (2021)

Article Rheumatology

Progressive interstitial lung disease in patients with systemic sclerosis-associated interstitial lung disease in the EUSTAR database

Anna-Maria Hoffmann-Vold et al.

Summary: This study utilized data from the European Scleroderma Trials And Research (EUSTAR) database to analyze the disease course, progression patterns, and predictive factors for progressive interstitial lung disease (ILD) in patients with systemic sclerosis-associated ILD (SSc-ILD). The results showed that male sex, higher modified Rodnan skin score, and reflux/dysphagia symptoms were the strongest predictive factors for forced vital capacity (FVC) decline over a 5-year period in SSc-ILD patients.

ANNALS OF THE RHEUMATIC DISEASES (2021)

Article Rheumatology

STRATUS: A Phase II Study of Abituzumab in Patients With Systemic Sclerosis-associated Interstitial Lung Disease

Dinesh Khanna et al.

Summary: The study aimed to investigate the effects of abituzurnab in systemic sclerosis-associated interstitial lung disease (SSc-ILD), but was terminated prematurely due to slow enrollment, preventing a detailed analysis of efficacy.

JOURNAL OF RHEUMATOLOGY (2021)

Article Rheumatology

Association of Autologous Hematopoietic Stem Cell Transplantation in Systemic Sclerosis With Marked Improvement in Health-Related Quality of Life

Nancy Maltez et al.

Summary: A study comparing SSc patients who underwent autologous HSCT with those who received conventional care found that the HSCT group had higher HRQoL scores in physical aspects but no significant differences in mental aspects. This study provides robust data supporting the physical benefits of autologous HSCT in patients with SSc.

ARTHRITIS & RHEUMATOLOGY (2021)

Review Rheumatology

Scleroderma epidemiology update

Leonardo Martin Calderon et al.

Summary: Global epidemiological studies on systemic sclerosis (SSc) show regional variations in prevalence, with the highest rates found among indigenous peoples in Canada. Age and sex differences influence disease severity and presentation. Future research may focus on personalized patient care and identifying high-risk populations for clinical trials.

CURRENT OPINION IN RHEUMATOLOGY (2021)

Review Medicine, General & Internal

Pulmonary hypertension in connective tissue diseases, new evidence and challenges

Madelon C. Vonk et al.

Summary: Pulmonary arterial hypertension is a lethal complication of different connective tissue diseases but treatment advancements have mainly benefited patients with idiopathic pulmonary arterial hypertension, while those with connective tissue disease-associated pulmonary arterial hypertension still face challenges. Current research focuses on improving early diagnostic, screening, and treatment options.

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION (2021)

Article Medicine, General & Internal

Inhaled Treprostinil in Pulmonary Hypertension Due to Interstitial Lung Disease

Aaron Waxman et al.

Summary: In patients with pulmonary hypertension due to interstitial lung disease, inhaled treprostinil significantly improved exercise capacity and clinical outcomes compared to placebo in a 16-week trial. Adverse events such as cough, headache, dyspnea, dizziness, nausea, fatigue, and diarrhea were commonly reported.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

Article Respiratory System

Serum markers of pulmonary epithelial damage in systemic sclerosis-associated interstitial lung disease and disease progression

Carmel J. W. Stock et al.

Summary: The study results indicate that serum KL-6 predicts decline in lung function in systemic sclerosis-associated interstitial lung disease (SSc-ILD) patients, suggesting its clinical utility in risk stratification for progressive SSc-ILD. KL-6 is particularly useful for predicting decline in lung function in patients who require prognostic assessment for SSc-ILD progression.

RESPIROLOGY (2021)

Editorial Material Rheumatology

Rituximab for the treatment of systemic sclerosis-interstitial lung disease

Michael Hughes et al.

Summary: This editorial discusses the study by Goswami et al., which suggests that rituximab may have therapeutic effects on systemic sclerosis-related interstitial lung disease.

RHEUMATOLOGY (2021)

Article Critical Care Medicine

Safety and Efficacy of B-Cell Depletion with Rituximab for the Treatment of Systemic Sclerosis-associated Pulmonary Arterial Hypertension A Multicenter, Double-Blind, Randomized, Placebo-controlled Trial

Roham T. Zamanian et al.

Summary: The study suggested that B-cell depletion therapy may have potential efficacy and safety for SSc-PAH. Low levels of RF, IL-12, and IL-17 may serve as promising predictors of rituximab response. Despite initially showing no significant difference in the primary analysis, the rituximab group demonstrated a statistically significant improvement in 6MWD at Week 24 when considering data through Week 48.

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE (2021)

Article Rheumatology

Systemic Sclerosis and Associated Interstitial Lung Disease in Ontario, Canada: An Examination of Prevalence and Survival Over 10 Years

Janet E. Pope et al.

Summary: This study in Ontario, Canada, used administrative data to estimate the prevalence and survival rates of SSc and SSc-ILD. The results confirmed that the prevalence of SSc-ILD falls within the threshold for rare diseases in Canada and showed that survival rates are lower in SSc patients, especially when ILD is present.

JOURNAL OF RHEUMATOLOGY (2021)

Article Critical Care Medicine

Pirfenidone in patients with progressive fibrotic interstitial lung diseases other than idiopathic pulmonary fibrosis (RELIEF): a double-blind, randomised, placebo-controlled, phase 2b trial

Juergen Behr et al.

Summary: This multicentre, double-blind, randomised, placebo-controlled trial aimed to evaluate the efficacy and safety of pirfenidone in patients with progressive fibrotic interstitial lung diseases. Results after 48 weeks showed a significantly lower decline in FVC % predicted in the pirfenidone group compared to placebo, suggesting that adding pirfenidone to existing treatment might attenuate disease progression in these patients.

LANCET RESPIRATORY MEDICINE (2021)

Article Rheumatology

Tofacitinib in the treatment of skin and musculoskeletal involvement in patients with systemic sclerosis, evaluated by ultrasound

Rositsa Valerieva Karalilova et al.

Summary: SSc patients have a markedly activated JAK/STAT signaling pathway. TOF is more effective than MTX in reducing skin and musculoskeletal involvement in SSc, with satisfactory safety.

RHEUMATOLOGY INTERNATIONAL (2021)

Article Health Care Sciences & Services

Rituximab as a Treatment Option after Autologous Hematopoietic Stem Cell Transplantation in a Patient with Systemic Sclerosis

Paul Gressenberger et al.

Summary: Systemic sclerosis (SSc) is a difficult-to-treat autoimmune disease characterized by vascular damage and organ fibrosis. Autologous hematopoietic stem cell transplantation (AHSCT) may be considered for high-risk SSc patients, but the need for additional immunosuppressive therapies such as rituximab (RTX) post-AHSCT remains unclear. This report highlights the potential efficacy of RTX in SSc patients who do not respond well to AHSCT, with improved clinical symptoms and organ functions observed after RTX treatment.

JOURNAL OF PERSONALIZED MEDICINE (2021)

Article Rheumatology

Sine scleroderma, limited cutaneous, and diffused cutaneous systemic sclerosis survival and predictors of mortality

Sebastien De Almeida Chaves et al.

Summary: This study confirms the high mortality of SSc in the long-term follow-up of patients from two hospitals. Male sex, DLCO <70%, cardiac involvement, and CRP > 5mg/l were identified as independent predictors of mortality. Non-systemic sclerosis-related deaths, particularly cardiovascular events, are more common than SSc-related deaths.

ARTHRITIS RESEARCH & THERAPY (2021)

Review Respiratory System

Assessment of recent evidence for the management of patients with systemic sclerosis-associated interstitial lung disease: a systematic review

Anna-Maria Hoffmann-Vold et al.

Summary: This systematic review provides evidence-based recommendations for the treatment of SSc-associated ILD. Risk factors, diagnosis tools, and immunosuppressive therapy were highlighted, but long-term efficacy and safety remain limited. Future research should focus on exploring novel therapies and biomarkers in well-controlled clinical studies.

ERJ OPEN RESEARCH (2021)

Review Rheumatology

Rituximab in the treatment of systemic sclerosis-related interstitial lung disease: a systematic review and meta-analysis

Rudra P. Goswami et al.

Summary: Treatment with RTX in SSc-ILD resulted in a significant improvement in both FVC and DLCO during the first year of treatment, with lower rates of infection compared to controls.

RHEUMATOLOGY (2021)

Review Rheumatology

Raynaud phenomenon and digital ulcers in systemic sclerosis

Michael Hughes et al.

NATURE REVIEWS RHEUMATOLOGY (2020)

Article Critical Care Medicine

Systemic sclerosis-associated interstitial lung disease

Apostolos Perelas et al.

LANCET RESPIRATORY MEDICINE (2020)

Article Critical Care Medicine

Tocilizumab in systemic sclerosis: a randomised, double-blind, placebo-controlled, phase 3 trial

Dinesh Khanna et al.

LANCET RESPIRATORY MEDICINE (2020)

Review Respiratory System

The need for a holistic approach for SSc-ILD - achievements and ambiguity in a devastating disease

Anna-Maria Hoffmann-Vold et al.

RESPIRATORY RESEARCH (2020)

Review Rheumatology

Management of systemic sclerosis-associated interstitial lung disease

David Roofeh et al.

CURRENT OPINION IN RHEUMATOLOGY (2019)

Article Medicine, General & Internal

Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease

Oliver Distler et al.

NEW ENGLAND JOURNAL OF MEDICINE (2019)

Article Rheumatology

Novel Imaging Approaches in Systemic Sclerosis-Associated Interstitial Lung Disease

Sydney B. Montesi et al.

CURRENT RHEUMATOLOGY REPORTS (2019)

Review Medicine, Research & Experimental

Endothelin receptor antagonism during preeclampsia: a matter of timing?

Emilie Hitzerd et al.

CLINICAL SCIENCE (2019)

Review Respiratory System

Screening for pulmonary arterial hypertension in systemic sclerosis

Jason Weatherald et al.

EUROPEAN RESPIRATORY REVIEW (2019)

Article Medicine, General & Internal

Nintedanib in Progressive Fibrosing Interstitial Lung Diseases

K. R. Flaherty et al.

NEW ENGLAND JOURNAL OF MEDICINE (2019)

Article Respiratory System

Haemodynamic definitions and updated clinical classification of pulmonary hypertension

Gerald Simonneau et al.

EUROPEAN RESPIRATORY JOURNAL (2019)

Article Respiratory System

Risk stratification and medical therapy of pulmonary arterial hypertension

Nazzareno Galie et al.

EUROPEAN RESPIRATORY JOURNAL (2019)

Review Rheumatology

Management of Raynaud's phenomenon in systemic sclerosis-a practical approach

Andreu Fernandez-Codina et al.

JOURNAL OF SCLERODERMA AND RELATED DISORDERS (2019)

Review Hematology

Autologous Hematopoietic Stern Cell Transplantation for Systemic Sclerosis: A Systematic Review and Meta-Analysis

Roni Shouval et al.

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION (2018)

Article Rheumatology

Venous Thromboembolism in Systemic Sclerosis: Prevalence, Risk Factors, and Effect on Survival

Sindhu R. Johnson et al.

JOURNAL OF RHEUMATOLOGY (2018)

Article Medicine, General & Internal

Myeloablative Autologous Stem-Cell Transplantation for Severe Scleroderma

K. M. Sullivan et al.

NEW ENGLAND JOURNAL OF MEDICINE (2018)

Article Rheumatology

Treatment Algorithms for Systemic Sclerosis According to Experts

Andreu Fernandez-Codina et al.

ARTHRITIS & RHEUMATOLOGY (2018)

Review Rheumatology

Update of EULAR recommendations for the treatment of systemic sclerosis

Otylia Kowal-Bielecka et al.

ANNALS OF THE RHEUMATIC DISEASES (2017)

Review Rheumatology

Digital ulcers in systemic sclerosis

Michael Hughes et al.

RHEUMATOLOGY (2017)

Article Rheumatology

Mapping and predicting mortality from systemic sclerosis

Muriel Elhai et al.

ANNALS OF THE RHEUMATIC DISEASES (2017)

Review Rheumatology

Standardization of the modified Rodnan skin score for use in clinical trials of systemic sclerosis

Dinesh Khanna et al.

JOURNAL OF SCLERODERMA AND RELATED DISORDERS (2017)

Editorial Material Rheumatology

BSR and BHPR guideline for the treatment of systemic sclerosis

Christopher P. Denton et al.

RHEUMATOLOGY (2016)

Article Respiratory System

Lung Transplant in Patients with Scleroderma Compared with Pulmonary Fibrosis Short- and Long-Term Outcomes

Maria M. Crespo et al.

ANNALS OF THE AMERICAN THORACIC SOCIETY (2016)

Article Medicine, General & Internal

Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension

N. Galie et al.

NEW ENGLAND JOURNAL OF MEDICINE (2015)

Article Rheumatology

Survival of Adults With Systemic Sclerosis Following Lung Transplantation A Nationwide Cohort Study

Elana J. Bernstein et al.

ARTHRITIS & RHEUMATOLOGY (2015)

Article Medicine, General & Internal

Autologous Hematopoietic Stem Cell Transplantation vs Intravenous Pulse Cyclophosphamide in Diffuse Cutaneous Systemic Sclerosis A Randomized Clinical Trial

Jacob M. van Laar et al.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2014)

Article Surgery

Fat Grafting to the Hand in Patients with Raynaud Phenomenon: A Novel Therapeutic Modality

Jonathan Bank et al.

PLASTIC AND RECONSTRUCTIVE SURGERY (2014)

Article Rheumatology

Prediction of Pulmonary Complications and Long-Term Survival in Systemic Sclerosis

Svetlana I. Nihtyanova et al.

ARTHRITIS & RHEUMATOLOGY (2014)

Article Rheumatology

Systemic sclerosis sine scleroderma: distinct features in a large Brazilian cohort

Roberta Goncalves Marangoni et al.

RHEUMATOLOGY (2013)

Article Rheumatology

Meta-Analysis of Healing and Prevention of Digital Ulcers in Systemic Sclerosis

Theresa Tingey et al.

ARTHRITIS CARE & RESEARCH (2013)

Review Immunology

Interstitial lung disease in systemic sclerosis

Guillaume Bussone et al.

AUTOIMMUNITY REVIEWS (2011)

Review Rheumatology

Systemic Sclerosis: Bilateral Improvement of Raynaud's Phenomenon with Unilateral Digital Sympathectomy

Amy Wasserman et al.

SEMINARS IN ARTHRITIS AND RHEUMATISM (2010)

Article Critical Care Medicine

Interstitial lung disease in systemic sclerosis - A simple staging system

Nicole S. L. Goh et al.

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE (2008)

Article Rheumatology

Changes in causes of death in systemic sclerosis, 1972-2002

Virginia D. Steen et al.

ANNALS OF THE RHEUMATIC DISEASES (2007)

Article Respiratory System

Anticoagulation in pulmonary arterial hypertension: a qualitative systematic review

S. R. Johnson et al.

EUROPEAN RESPIRATORY JOURNAL (2006)

Article Critical Care Medicine

Thrombotic arteriopathy and anticoagulation in pulmonary hypertension

Sindhu R. Johnson et al.

Article Medicine, General & Internal

Cyclophosphamide versus placebo in scleroderma lung disease

Donald P. Tashkin et al.

NEW ENGLAND JOURNAL OF MEDICINE (2006)

Article Pharmacology & Pharmacy

Bosentan decreases the plasma concentration of sildenafil when coprescribed in pulmonary hypertension

GA Paul et al.

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY (2005)

Article Rheumatology

Comparison between iloprost and alprostadil in the treatment of Raynaud's phenomenon

B Marasini et al.

SCANDINAVIAN JOURNAL OF RHEUMATOLOGY (2004)