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Objectives To explore prognostic and predictive markers of SSc-associated interstitial lung disease (SSc-ILD) outcomes in a phase 3 trial (focuSSced) and prognostic markers in a real-world cohort (SMART). Methods The focuSSced SSc-ILD subgroup included 68 of 106 placebo-treated and 68 of 104 tocilizumab-treated patients. The SMART cohort included 505 patients with SSc-ILD. Linear mixed-effect models were used to identify factors associated with change in forced vital capacity (FVC). Kaplan–Meier estimation and Cox regression were used for time-to-event analyses. Results In placebo-treated focuSSced patients, sex was a significant prognostic factor for FVC decline; males had increased risk for absolute decline ≥10% in percent-predicted FVC (ppFVC) and 0.22% faster weekly FVC decline than females (P   =  0.0001). FVC was 9.8% lower in patients with CRP >6 mg/ml vs those with CRP ≤6 mg/ml (P  = 0.0059). Tocilizumab reduced the risk for ≥10% decline in ppFVC in patients who were male, had earlier disease (<2 years duration), had IL-6 levels <10 pg/ml, or had anti-topoisomerase antibodies (ATA). In the SMART cohort, prognostic factors for ppFVC <70% were male sex, ATA, and low baseline FVC. Males had 3.3% lower FVC 1 year after disease onset (P  < 0.001) and 0.6% faster yearly decline (P  = 0.03) than females. Conclusion Prognostic markers in SSc-ILD were similar between focuSSced and SMART. Male sex and inflammatory markers were associated with lower FVC but IL-6 ≥10 pg/ml was not predictive of response to tocilizumab. Trial Registration ClinicalTrials.gov: NCT02453256. [ABSTRACT FROM AUTHOR]

Objective: Pulmonary hypertension (PH) is a serious complication of systemic sclerosis (SSc). In this study, we explored the prediction of short‐term risk for PH using serial pulmonary function tests (PFTs) and other disease features. Methods: SSc patients in whom disease onset occurred ≥10 years prior to data retrieval and for whom autoantibody specificity and PFT data were available were included in this study. Mixed‐effects modeling was used to describe changes in PFTs over time. Landmarking was utilized to include serial assessments and stratified Cox proportional hazards regression analysis with landmarks as strata was used to develop the PH prediction models. Results: We analyzed data from 1,247 SSc patients, 16.3% of whom were male and 35.8% of whom had diffuse cutaneous SSc. Anticentromere, antitopoisomerase, and anti–RNA polymerase antibodies were observed in 29.8%, 22.0%, and 11.4% of patients, respectively, and PH developed in 13.6% of patients. Over time, diffusing capacity for carbon monoxide (DLco) and carbon monoxide transfer coefficient (Kco) declined in all SSc patients (up to 1.5% per year) but demonstrated much greater annual decline (up to 4.5% and 4.8%, respectively) in the 5–7 years preceding PH diagnosis. Comparisons between multivariable models including either DLco, Kco, or forced vital capacity (FVC)/DLco ratio, demonstrated that both absolute values and change over the preceding year in those measurements were strongly associated with the risk of PH (hazard ratio [HR] 0.93 and 0.76 for Kco and its change; HR 0.90 and 0.96 for DLco and its change; and HR 1.08 and 2.01 for FVC/DLco ratio and its change; P < 0.001 for all). The Kco‐based model had the greatest discriminating ability (Harrell's C‐statistic 0.903). Conclusion: Our findings strongly support the importance of PFT trends over time in identifying patients at risk of developing PH. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to explore outcomes in a cohort of dcSSc patients fulfilling eligibility criteria for stem cell transplantation (SCT) studies but receiving standard immunosuppression. Methods From a large single-centre dcSSc cohort (n  = 636), patients were identified using the published SCT trials' inclusion criteria. Patients meeting the trials' exclusion criteria were excluded. Results Of the 227 eligible patients, 214 met the inclusion criteria for ASTIS (Autologous Stem Cell Transplantation International Scleroderma), 82 for SCOT (Scleroderma: Cyclophosphamide Or Transplantation) and 185 for the UPSIDE (UPfront autologous haematopoietic Stem cell transplantation vs Immunosuppressive medication in early DiffusE cutaneous systemic sclerosis) trial, and 66 were excluded based on age >65 years, low diffusing capacity of the lungs for carbon monoxide (DLco), pulmonary hypertension or creatinine clearance <40 ml/min. The mean follow-up time was 12 years (s. d. 7). Among the eligible patients, 103 (45.4%) died. Survival was 96% at 2 years, 88% at 5 years, 73% at 10 years and 43% at 20 years. Compared with this 'SCT-eligible' cohort, those patients who would have been excluded from SCT trials had a worse long-term survival (97% at 2 years, 77% at 5 years, 52% at 10 years and 15% at 20 years, log rank P  < 0.001). Excluded patients also had a significantly worse long-term event-free survival. Hazard of death was higher in patients with higher age at onset [hazard ratio (HR) 1.05, P  < 0.001], higher ESR at baseline (HR 1.01, P  = 0.025) and males (HR 2.12, P  = 0.008). Conclusion SCT inclusion criteria identify patients with poor outcome despite current best practice treatment. Patients meeting the inclusion criteria for SCT but who would have been excluded from the trials because of age, pulmonary hypertension, poor kidney function or DLco <40% had worse outcomes. [ABSTRACT FROM AUTHOR]

Objectives To assess the prevalence and burden of SSc-related gastrointestinal dysfunction (SSc-GI) and to evaluate associations with demographic, clinical and serological characteristics. Methods Patients completed the UCLA SCTC GIT 2.0 questionnaire for SSc-GI disease to assess the burden of GI disease across multiple functional and psychological domains. Questionnaire scores were assessed using non-parametric and quantile regression analyses. Results Our cohort included 526 patients with SSc, with a typical distribution of disease-associated autoantibodies (ACA, ARA, ATA, PM-Scl, U1RNP, U3RNP). We demonstrated associations between hallmark antibodies and the domain-specific burden of GI disease. In particular, ACA, ARA and ENA-negative demonstrated increased SSc-GI disease burden, while PM-Scl conferred relative protection. In a distributional analysis, associations with autoantibodies were particularly marked in those with the highest burden of GI disease. Conclusion There is a significant burden of SSc-GI disease in patients with SSc; reflux and bloating symptoms are most prominent. SSc hallmark antibodies may predict increased risk of SSc-GI disease, in particular ACA and ARA, while PM-Scl may be protective. [ABSTRACT FROM AUTHOR]

Objective To investigate the association between proton pump inhibitor (PPI) use and the presence and severity of calcinosis in SSc. Methods We analysed data from two SSc cohorts from a single centre. Cohort 1 included 199 patients reviewed over 10 years, for whom retrospective data on PPI use and calcinosis were available. Cohort 2 was recruited prospectively and included 215 consecutive patients, who underwent clinical assessment. Outcomes of interest were presence of current calcinosis (CC) or calcinosis at any time (CAT). Results The cohort 1 data analysis showed that among patients on standard dose PPI 20% had calcinosis, while in those on high doses of PPI calcinosis was present in 39% (P  = 0.003). Analysis of the data from cohort 2 confirmed these findings, demonstrating that the odds of CAT increased significantly with longer PPI exposure [odds ratio (OR) 1.04, 95% CI: 1.02, 1.06; P  < 0.001], longer disease duration (OR 1.08, 95% CI: 1.05, 1.12; P  < 0.001) and greater age (OR 1.03, CI: 1.01, 1.05; P  = 0.010). Multivariable logistic regression showed that higher exposure to PPI remained a significant predictor of calcinosis, with PPI exposure >10 years increasing the risk of CAT >6-fold, compared with no PPI (OR 6.37, 95% CI: 1.92, 21.17; P  = 0.003) after adjusting for disease duration and antibodies. Conclusion We confirm a significant association between high PPI exposure with severity of calcinosis in SSc. Given the clinical impact of calcinosis and reflux in SSc, PPI exposure as a potentially modifiable risk factor for calcinosis requires further evaluation. [ABSTRACT FROM AUTHOR]

Objectives: Systemic sclerosis (SSc)-interstitial lung disease (ILD) is one of the leading causes of mortality in SSc. Data from randomised controlled trials (RCTs) supports rituximab and tocilizumab monotherapy but there is limited data regarding their use for those who fail standard immunomodulatory therapies., Methods: SSc patients treated with rituximab or tocilizumab were retrospectively identified in a single centre cohort. Linear mixed effect models were used to analyse before and after treatment lung function trajectory and identify patient characteristics associated with treatment response., Results: 127 patients were included for analysis. 51 of 94 (51.4%) and 13 of 33 (39.4%) of the rituximab and tocilizumab cohorts respectively were receiving concurrent mycophenolate mofetil. Pre-treatment decline in absolute change %FVC/year and %DLCO/year respectively, was similar in both cohorts (-3.2% and -4.0% rituximab and -3.2% and -3.6% tocilizumab). Both treatments resulted in lung function stabilisation (%FVC/year and %DLCO/year: 1.2% and +0.2% rituximab cohort, 1.0% and 1.0% tocilizumab cohort). Anti-topoisomerase antibody (ATA) positive patients had a significant response on %FVC/year to tocilizumab compared with ATA negative patients. Gender had a significant impact on %FVC/year response to rituximab, with males responding to a greater degree than females. Age, ILD extent and skin subset had no impact on treatment response., Conclusion: Combination rituximab or tocilizumab with background immunosuppressive therapy is associated with stabilisation in lung function trajectory among those who remain refractory to standard immunosuppressives. Specific patient characteristics have an impact on lung function response. Improved FVC response among ATA patients receiving tocilizumab validate data from RCTs., (© The Author(s) 2025. Published by Oxford University Press on behalf of the British Society for Rheumatology.)