ERS/EULAR clinical practice guidelines for connective tissue diseases associated interstitial lung disease.

Background: Interstitial lung disease (ILD) is a frequent manifestation of connective tissue diseases (CTDs) and is associated with high morbidity and mortality. Clinical practice guidelines to standardise screening, diagnosis, treatment and follow-up for CTD-ILD are of high importance for optimised patient care.

Methods: A European Respiratory Society and European Alliance of Associations for Rheumatology task force committee, composed of pulmonologists, rheumatologists, pathologists, radiologists, methodologists and patient representatives, developed recommendations based on PICO (Patients, Intervention, Comparison, Outcomes) questions with grading of the evidence according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) methodology and complementary narrative questions agreed on by both societies.

ERS/EULAR clinical practice guidelines for connective tissue disease-associated interstitial lung diseaseDeveloped by the task force for connective tissue disease-associated interstitial lung disease of the European Respiratory Society (ERS) and the European Alliance of Associations for Rheumatology (EULAR)Endorsed by the European Reference Network on rare respiratory diseases (ERN-LUNG).

Background: Interstitial lung disease (ILD) is a frequent manifestation of connective tissue diseases (CTDs) and is associated with high morbidity and mortality. Clinical practice guidelines to standardise screening, diagnosis, treatment and follow-up for CTD-ILD are of high importance for optimised patient care.

Methods: A European Respiratory Society and European Alliance of Associations for Rheumatology task force committee, composed of pulmonologists, rheumatologists, pathologists, radiologists, methodologists and patient representatives, developed recommendations based on PICO (Patients, Intervention, Comparison, Outcomes) questions with grading of the evidence according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) methodology and complementary narrative questions agreed on by both societies.

Deep hierarchical subtyping of multi-organ systemic sclerosis trajectories - a EUSTAR study.

Systemic 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.

Effectiveness and safety of rituximab across the four phenotypes of IgG4-related disease: a European multi-center cohort study of 115 patients.

Objective: Assess relative effectiveness and safety of rituximab (RTX) across the four phenotypes of IgG4-related disease (IgG4-RD).

Methods: We included phenotypically defined adult IgG4-RD patients treated with RTX +/- glucocorticoids (GC) who had evaluable data at 6 months on the composite primary outcome, which included: (i) treatment response (>= 2-point decline in responder index (RI)); (ii) absence of flare; and (iii) GC dose <= 7.5 mg prednisolone.

A screening tool to detect interstitial lung disease in systemic sclerosis: the ILD-RISC Score.

Objective: As a screening tool for the presence of systemic sclerosis-associated interstitial lung disease (SSc-ILD) on high-resolution computed tomography (HRCT) is missing, we aimed to develop the ILD-RISC score, a risk algorithm to guide physicians in ordering HRCTs, with specific focus on follow-up visits.

Methods: The nominal group technique was used to select items for the multivariable logistic regression with backward selection. The ILD-RISC score was developed from baseline visits of the derivation cohort.

Emphysema elevates the DETECT scores: impact on pulmonary hypertension screening and diagnosis in systemic sclerosis.

Objectives: Combined pulmonary fibrosis and emphysema (CPFE) predicts unfavourable outcomes in systemic sclerosis (SSc). CPFE and emphysema are associated with pulmonary function tests (PFTs) abnormalities. As screening algorithms for pulmonary hypertension include PFTs, we aimed to assess whether CPFE and emphysema affect the performance of the DETECT algorithm to select patients for right heart catheterization (RHC).

The serum levels of specific autoantibodies in systemic sclerosis predict a more severe skin involvement.

Background: Systemic sclerosis is a severe autoimmune disease characterized by fibrosis of the skin and internal organs. Systemic sclerosis is associated with the presence of three specific autoantibodies: anti-topoisomerase I, anti-centromere, and anti-RNA polymerase III autoantibodies, which have also been identified as prognostic factors. However, it remains unknown whether the prognosis also varies based on their serum levels.

The diagnostic utility of lung ultrasound in the assessment of interstitial lung disease associated with rheumatoid arthritis.

Background: To investigate the diagnostic accuracy of lung ultrasound (LUS) for interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA).

Methods: This retrospective study included patients over 18 years with RA evaluated at the Department of Rheumatology and Immunology of Shantou Central Hospital. All patients underwent chest high-resolution computed tomography (HRCT) and LUS within one month.

'Am I doing this right?' Physician perceptions of the global assessment in clinical trials of systemic sclerosis.

Objectives: Physician global assessments (PhyGAs) are commonly performed in randomised controlled trials (RCTs) in systemic sclerosis (SSc). However, there is no single PhyGA applied across RCTs. We performed an exploratory qualitative study to explore perceptions of the PhyGA, its role in RCTs and how physicians perform their own assessment.

Lung function and skin fibrosis changes as predictors of survival in SSc-associated interstitial lung disease: a EUSTAR study.

Objectives: This study assessed how changes in lung function, skin fibrosis and digital ulceration (DU) burden predict mortality in patients with SSc-associated interstitial lung disease (SSc-ILD), the leading cause of death in SSc.

Methods: Adult SSc-ILD patients from the European Scleroderma Trials and Research (EUSTAR) database enrolled since January 2009 with a date of diagnosis, a follow-up visit for change evaluation within 12 months plus a further visit, or mortality information were eligible. Twelve-month changes in lung function (per cent predicted forced vital capacity [FVC%pred] and diffusing capacity of the lungs for carbon monoxide [DLCO%pred]), modified Rodnan skin score (mRSS) and change in DU burden were assessed for associations with survival, using multivariable Cox regression analyses adjusted for age, sex, smoking status and immunosuppressive therapy.

Nerandomilast in Patients with Progressive Pulmonary Fibrosis.

Background: Nerandomilast (BI 1015550) is an orally administered preferential inhibitor of phosphodiesterase 4B with antifibrotic and immunomodulatory properties. Nerandomilast has been shown to slow the progression of idiopathic pulmonary fibrosis, but an assessment of its effects in other types of progressive pulmonary fibrosis is needed.

Methods: In a phase 3, double-blind trial, we randomly assigned patients with progressive pulmonary fibrosis in a 1:1:1 ratio to receive nerandomilast at a dose of 18 mg twice daily, nerandomilast at a dose of 9 mg twice daily, or placebo, with stratification according to background therapy (nintedanib vs.

Predicting the risk of subsequent progression in patients with systemic sclerosis-associated interstitial lung disease with progression: a multicentre observational cohort study.

Background: In patients with systemic sclerosis, it is common practice to treat interstitial lung disease (ILD) in patients in whom progression has already occurred. We sought to clarify whether observed progression of systemic sclerosis-associated ILD confers risk for subsequent progression.

Methods: In this multicentre observational cohort study, based on an analysis of prospectively collected data, we included patients with systemic sclerosis-associated ILD aged 18 years or older at diagnosis, who fulfilled the 2013 American College of Rheumatology-European Association of Alliances in Rheumatology systemic sclerosis classification criteria.

Validation of a semi-quantitative method to assess interstitial lung disease severity and progression in systemic sclerosis by standard and low-dose HRCT scans.

Background: While the presence of distinct imaging abnormalities by high-resolution CT (HRCT) defines interstitial lung disease (ILD), there is a relative lack of validated methods to quantify these abnormalities in clinical practice, limiting ILD severity and progression assessments. We aimed to validate a semi-quantitative method for lung fibrosis assessment in patients with systemic sclerosis associated ILD (SSc-ILD) by standard and low-dose HRCT, considering lung structure and function as integral components of ILD evaluation.

Methods: SSc patients from Oslo and Zurich with HRCT images, pulmonary function tests, including forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO) and the 6-minute walk test with oxygen (O) desaturation were enrolled.

Evaluation of Systemic Sclerosis Primary Heart Involvement and Chronic Heart Failure in the European Scleroderma Trials and Research Cohort.

Background: Systemic sclerosis (SSc) primary heart involvement (SSc-pHI) is one of the leading causes of mortality in SSc. We aimed to evaluate risk factors for SSc-pHI and its progression and the outcomes in the EUSTAR (European Scleroderma Trials and Research) cohort.

Methods: SSc-pHI was defined according to the World Scleroderma Foundation/Heart Failure Association definition.

How to build a framework to establish a patient research partner network in rheumatology research: a report of a 2-year implementation project.

Background: Patient research partners (PRPs) are people living with a relevant disease who actively contribute to research. Their contribution is beneficial for any research project. Although the inclusion of PRPs in rheumatology research is increasingly recommended, its practical implementation, particularly in translational research, remains limited .

Faecal microbiota transplantation in patients with systemic sclerosis and lower gastrointestinal tract symptoms in Norway (ReSScue): a phase 2, randomised, double-blind, placebo-controlled trial.

Background: Gastrointestinal tract involvement is highly prevalent in systemic sclerosis, with few treatment options. We assessed the efficacy and safety of faecal microbiota transplantation using standardised anaerobic cultivated human intestinal microbiome (ACHIM) as a novel treatment option for patients with systemic sclerosis and symptomatic lower gastrointestinal tract involvement.

Methods: In this phase 2, randomised, double-blind, placebo-controlled trial done at four university hospitals in Norway, we enrolled adults aged 18-85 years with systemic sclerosis and moderate-to-severe lower gastrointestinal tract symptoms (bloating or diarrhoea).

Post hoc comparison of the effectiveness of tocilizumab, rituximab, mycophenolate mofetil, and cyclophosphamide in patients with SSc-ILD from the EUSTAR database.

Objectives: Tocilizumab (TCZ), rituximab (RTX), mycophenolate mofetil (MMF), and cyclophosphamide (CYC) are the immunosuppressants (IS) most frequently used for systemic sclerosis-associated interstitial lung disease (SSc-ILD). This post hoc study aimed to compare their effectiveness in patients with SSc-ILD from the European Scleroderma Trials and Research (EUSTAR) database.

Methods: We included radiologically confirmed SSc-ILD patients with treatment records for TCZ, RTX, MMF, or CYC.

A comparative analysis of risk stratification tools in SSc-associated pulmonary arterial hypertension: a EUSTAR analysis.

Objectives: The 2022 European Society of Cardiology and European Respiratory Society (ESC/ERS) guidelines for pulmonary arterial hypertension (PAH) recommend risk stratification to optimize management. However, the performance of generic PAH risk stratification tools in patients with SSc-associated PAH remains unclear. Our objective was to identify the most accurate approach for risk stratification at SSc-PAH diagnosis.

EULAR recommendations for the treatment of systemic sclerosis: 2023 update.

Objectives: To update the 2017 European Alliance of Associations for Rheumatology (EULAR) recommendations for treatment of systemic sclerosis (SSc), incorporating new evidence and therapies.

Methods: An international task force was convened in line with EULAR standard operating procedures. A nominal group technique exercise was performed in two rounds to define questions underpinning a subsequent systematic literature review.

Gastroesophageal reflux disease is associated with a more severe interstitial lung disease in systemic sclerosis in the EUSTAR cohort.

Objectives: Gastroesophageal reflux disease (GERD) is frequent in systemic sclerosis (SSc) and could predict progression of interstitial lung disease (ILD). We aimed to analyse (1) the prevalence of GERD among SSc-ILD patients, (2) its association with disease characteristics and (3) predictive factors for ILD progression in SSc-ILD patients with GERD.

Methods: SSc patients from the EUSTAR database with ILD were included.

Rationale for phosphodiesterase-4 inhibition as a treatment strategy for interstitial lung diseases associated with rheumatic diseases.

Interstitial lung disease (ILD) associated with rheumatoid arthritis or with connective tissue diseases such as systemic sclerosis can be collectively named systemic autoimmune rheumatic disease-associated ILDs (SARD-ILDs) or rheumatic musculoskeletal disorder-associated ILDs. SARD-ILDs result in substantial morbidity and mortality, and there is a high medical need for effective therapies that target both fibrotic and inflammatory pathways in SARD-ILD. Phosphodiesterase 4 (PDE4) hydrolyses cyclic AMP, which regulates multiple pathways involved in inflammatory processes.

A Phase II study of avenciguat, a novel soluble guanylate cyclase activator, in patients with systemic sclerosis: Study design and rationale of the VITALISScE™ study.

Introduction: Systemic sclerosis is a rare autoimmune connective tissue disease characterised by (1) microvasculopathy; (2) immune dysregulation; and (3) progressive fibrosis of the skin and internal organs. Soluble guanylate cyclase plays an important role in maintaining vascular and immunological homeostasis and preventing organ fibrosis. Pharmacological modulation of soluble guanylate cyclase with soluble guanylate cyclase stimulators has shown anti-inflammatory and antifibrotic effects in animal models of systemic sclerosis, with a trend towards clinical efficacy in a Phase II study (RISE-SSc).

A versatile role for lung ultrasound in systemic autoimmune rheumatic diseases related pulmonary involvement: a narrative review.

Systemic autoimmune rheumatic diseases (SARDs) related pulmonary disease is highly prevalent, with variable clinical presentation and behavior, and thus is associated with poor outcomes and negatively impacts quality of life. Chest high resolution computed tomography (HRCT) is still considered a fundamental imaging tool in the screening, diagnosis, and follow-up of pulmonary disease in patients with SARDs. However, radiation exposure, economic burden, as well as lack of point-of-care CT equipment limits its application in some clinical situation.