Background Autologous haematopoietic stem cell transplantation (HSCT) improves survival in systemic sclerosis (SSc) with poor prognosis, but is hampered by treatment-related mortality (TRM). Objective To evaluate event-free survival (EFS), TRM, response to treatment, disease progression and patient characteristics associated with events. Methods All patients treated with HSCT for SSc in The Netherlands until 2017 (n=92) were included. Data on skin involvement (modified Rodnan skin score (mRSS), pulmonary function (forced vital capacity (FVC) and diffusion capacity of the lungs for carbon monoxide (DLCO)), extent of interstitial lung disease on high-resolution CT using Goh scores and left ventricular ejection fraction (LVEF) were collected at baseline, 1, 2 and 5 years. Occurrence of events, defined as death or major organ failure, were collected until 2019. As control, a comparison between patients treated with cyclophosphamide (CYC) and patients with HSCT who participated in the Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial was performed. Results Median follow-up was 4.6 years. EFS estimates at 5, 10 and 15 years were 78%, 76% and 66%, respectively. Twenty deaths occurred. Mean FVC, DLCO, mRSS and Goh scores all improved significantly. Disease progression occurred in 22 patients. Frequency of TRM decreased over time and occurred more often in males. Events were independently associated with male sex, LVEF <50% and older age. In ASTIS, patients treated with HSCT (n=23) 7 events occurred versus 13 in the CYC group (n=22). Conclusion Our data confirm long-term efficacy of HSCT in improving survival, skin and lung involvement in SSc. Male sex, lower LVEF and older age at baseline were identified as risk factors for events.

Immune mediated inflammatory diseases (IMIDs) have similarities in pathophysiology and treatment. Not much is known, however, about health-related quality of life (HR-QoL) in IMIDs. We assessed and compared HR-QoL, using the validated EuroQoL 5-dimensions 5-levels questionnaire, in an observational cohort comprising 530 patients (67.5% female, mean age 49 years (95% CI 35.9-50.9), mean disease duration 31.0 months (95% CI 27.2-34.8)), with the following IMIDs: connective tissue diseases (32.6%), uveitis (20.8%), inflammatory arthritis (17.7%), psoriasis (15.5%), vasculitis (6.2%), primary antiphospholipid syndrome (4.2%), and autoinflammatory diseases (2.8%). Patients used either no anti-inflammatory therapy (31.5%), monotherapy (28.7%), or a combination of anti-inflammatory drugs (39.8%). The mean HR-QoL utility score was 0.75 (95% CI 0.72-0.78). Multinominal logistic regression analysis showed a statistically significant association between a very low HR-QoL (utility score (<0.70)) and female sex, rheumatological IMID or psoriasis, smoking or having smoked in the past, and current biological disease modifying anti-rheumatic drugs use.

Introduction Systemic sclerosis (SSc) is a chronic, autoimmune connective tissue disease associated with high morbidity and mortality, especially in diffuse cutaneous SSc (dcSSc). Currently, there are several treatments available in early dcSSc that aim to change the disease course, including immunosuppressive agents and autologous haematopoietic stem cell transplantation (HSCT). HSCT has been adopted in international guidelines and is offered in current clinical care. However, optimal timing and patient selection for HSCT are still unclear. In particular, it is unclear whether HSCT should be positioned as upfront therapy or rescue treatment for patients refractory to immunosuppressive therapy. We hypothesise that upfront HSCT is superior and results in lower toxicity and lower long-term medical costs. Therefore, we propose this randomised trial aiming to determine the optimal treatment strategy for early dcSSc by comparing two strategies used in standard care: (1) upfront autologous HSCT versus (2) immunosuppressive therapy (intravenous cyclophosphamide pulse therapy followed by mycophenolate mofetil) with rescue HSCT in case of treatment failure. Methods and analysis The UPSIDE (UPfront autologous hematopoietic Stem cell transplantation vs Immunosuppressive medication in early DiffusE cutaneous systemic sclerosis) study is a multicentre, randomised, open-label, controlled trial. In total, 120 patients with early dcSSc will be randomised. The primary outcome is event-free survival at 2 years after randomisation. Secondary outcomes include serious adverse events, functional status and health-related quality of life. We will also evaluate changes in nailfold capillaroscopy pattern, pulmonary function, cardiac MR and high-resolution CT of the chest. Follow-up visits will be scheduled 3-monthly for 2 years and annually in the following 3 years. Ethics and dissemination The study was approved by the Dutch Central Committee on Research Concerning Human Subjects (NL72607.041.20). The results will be disseminated through patient associations and conventional scientific channels. Trial registration numbers NCT04464434; NL 8720.

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. Data from 5741 patients with SSc in the EUSTAR cohort were analyzed. Additional cardiovascular data were collected from a subcohort of 838 patients with SSc. Lasso regression was used for risk factor analyses. Kaplan–Meier estimator was used for survival analyses. Progression of SSc‐pHI was evaluated by a study definition developed by rheumatology and cardiology experts. Results: Risk factors for the presence of SSc‐pHI comprised skeletal muscle atrophy (odds ratio [OR], 2.00 [95% CI, 1.00–2.68]), age (OR, 1.91 [95% CI, 1.73–2.03]), male sex (OR, 1.77 [95% CI, 1.42–2.05]), swollen joints (OR, 1.70 [95% CI, 1.47–1.98]), skeletal muscle weakness (OR, 1.38 [95% CI, 1.00–1.85]), and tendon friction rubs (OR, 1.46 [95% CI, 1.00–1.77]) (n=3276). Telangiectasia (OR, 2.10 [95% CI, 1.38–2.72]), intestinal symptoms (OR, 1.70 [95% CI, 1.04–2.42]), age (OR, 1.47 [95% CI, 1.21–1.62]), and antitopoisomerase I antibodies (OR, 1.37 [95% CI, 1.00–1.77]) were associated with an increased risk for new onset of SSc‐pHI (n=1000). Survival rate was significantly lower in patients with SSc‐pHI than in those without ( P value <0.0001, n=3768). Patients with SSc‐pHI had a lower survival rate than patients with interstitial lung disease (n=3365). Swollen joints were associated with an increased risk of progressive SSc‐pHI (OR, 2.49 [95% CI, 1.79–3.52]) (n=595). Tendon friction rubs (OR, 1.21 [95% CI, 0.94–1.90]) increased the risk of heart failure with preserved ejection fraction in patients with SSc‐pHI. Conclusions: We defined progressive SSc‐pHI and identified risk factors for new onset and progression of SSc‐pHI and for SSc‐pHI‐associated heart failure with preserved ejection fraction in the largest cohort with SSc. These findings may guide patient stratification for diagnostic workup and therapy.

Systemic sclerosis (SSc) is a chronic autoimmune disease with multiorgan involvement.

Immune-mediated rheumatologic and musculoskeletal diseases (RMDs) comprise a heterogeneous group of systemic conditions that affect the connective tissues of the musculoskeletal system and internal organs. Immune-mediated RMDs are driven by chronic autoimmune responses and typically require continuous or repeated administration of immunosuppressive or biologic disease-modifying drugs. Although generally effective, these therapies can cause both short- and long-term side effects and may fail to control the disease with risk of irreversible tissue damage. For such patients, haematopoietic stem cell transplantation (HSCT) has been successfully employed over the past 30 years, but this procedure requires caution due to significant side effects. To address these aspects, updated recommendations for the use of HSCT in RMDs have been developed in collaboration with an international expert panel from the European Society for Blood and Marrow Transplantation (EBMT). The panel reviewed all available evidence regarding HSCT application since 2004. Based on this review, EBMT expert-based consensus recommendations were formulated to guide best practices and ensure high-quality patient care. These recommendations include detailed indications, contraindications, and cautionary notes specific to each RMD, along with comprehensive protocols for diagnostic work-up. They are intended to support clinicians, scientists, patients, and caregivers in the field of RMDs.