2026-06-27 | High-intensity immunosuppression versus modern standard care in poor-prognosis diffuse cutaneous systemic sclerosis: A propensity-matched study.
Purpose: The 2023 EULAR update recommends autologous hematopoietic stem-cell transplantation preceded by high-intensity immunosuppression (HI-IS/HSCT) for selected poor-prognosis early diffuse cutaneous systemic sclerosis (dcSSc). As real-world data remain scarce, we compared 5-year outcomes of HI-IS/HSCT recipients with propensity-matched controls receiving standard care. Because undergoing HI-IS/HSCT identifies poor-prognosis systemic sclerosis (SSc), we compared their 5-year outcomes with those of propensity-matched dcSSc controls receiving standard care. This retrospective multicenter study analyzed ACR/EULAR-2013 dcSSc patients treated after 2013 from the Greater Paris University Hospitals and French national registry. Patients had poor-prognosis SSc defined by early disease and rapid skin progression or organ involvement. HI-IS/HSCT recipients were matched 1:1 with conventional immunosuppression controls using nearest-neighbor 20-variable propensity scores (covering demographics, antibodies, organ involvement, and prior treatments). Outcomes included overall survival (OS), event-free survival (EFS), progression-free survival (PFS), and toxicities at 60 months. Exploratory multivariable logistic regression identified predictors of EFS. We analyzed 100 patients, equally divided between the HI-IS/HSCT and control groups. Five-year OS was similar (90%) in both groups. However, HI-IS/HSCT was associated with significantly improved 5-year event-free survival (76% vs 46%, p = 0.021) and progression-free survival (82% vs 40%, p = 0.001), a more favorable Global Rank Composite Score (p = 0.001), greater skin improvement (p < 0.001), and stabilization of FVC (p = 0.034) compared with controls. Prior DMARD burden was significantly lower in the transplant group (median 1 vs 2, p < 0.0001). Conditioning containing fludarabine/rituximab showed a non-significant trend towards higher EFS compared to CYC + ATG alone (82.6% vs 66.7%, p = 0.33). HI-IS/HSCT caused higher grade ≥4 toxicities (36% vs 8%, p < 0.001), with a 2% procedure-related mortality. Older age and pre-existing cardiac involvement were independently associated with worse EFS after transplant. In patients with poor-prognosis dcSSc, 5-year overall survival was high and similar between HI-IS/HSCT and modern conventional care. However, HI-IS/HSCT provided significantly superior event-free and progression-free survival, skin improvement, and pulmonary stabilization. These findings support early HSCT as a highly effective disease-stabilizing therapy in carefully selected patients, provided they undergo rigorous cardiac screening.
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2026-06-22 | Pruritus associated with systemic sclerosis: a systematic review of treatment-based clinical trials.
This paper aims to examine the latest research on treatments for itch (pruritus) in people with systemic sclerosis (SSc), identify areas where information is lacking, and propose suggestions for future studies.A comprehensive literature search was performed in PubMed and Scopus in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify studies evaluating therapeutic interventions for pruritus in SSc. Eligible studies included randomized controlled trials, cohort studies, and case series comprising a minimum of three patients. Data extraction encompassed study design, patient demographics, pruritus assessment instruments including validated and non-validated measures, and clinical outcomes. Studies were excluded if they concerned localized scleroderma, irrelevant populations, case reports, systematic reviews, lacking relevant outcome data, or incomplete trials. Ten studies met criteria, evaluating immunomodulatory agents, mast cell stabilizers, opioid receptor antagonist, and lysophosphatidic acid receptor antagonists. Pruritus assessment varied and was often secondary to fibrosis outcomes. Oral lenabasum improved pruritus in a phase II trial; low-dose opioid receptor modulators and rituximab also showed qualitative improvement. Pruritus is a frequently overlooked yet clinically significant symptom in systemic sclerosis (SSc) that negatively impacts patients' quality of life. Existing evidence regarding effective therapeutic options remains limited. Future research should prioritize pruritus as a predefined outcome and utilize validated assessment instruments to inform treatment strategies and enhance patient quality of life.
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2026-06-19 | Efficacy of different pharmacological therapies for diffuse cutaneous systemic sclerosis: a systematic review and network meta-analysis.
This study aims to compare the effectiveness of different pharmacological therapies for diffuse cutaneous systemic sclerosis (dcSSc) through a network meta-analysis (NMA). Randomized controlled trials (RCTs) on pharmacological interventions for dcSSc were systematically searched in PubMed, Embase, Cochrane Library, and Web of Science up to 2026. A Bayesian network meta-analysis was carried out using Markov Chain Monte Carlo (MCMC) methods via R software and its GeMtc package. Outcomes assessed included Modified Rodnan Skin Score (MRSS), pulmonary functions (forced vital capacity [FVC], and diffusing capacity of the lung for carbon monoxide [DLCO]), and Health Assessment Questionnaire (HAQ). Effect sizes were reported as standardized mean differences (SMDs) with corresponding 95% credible intervals (95% CrIs). A total of 20 RCTs involving 1,760 patients and 16 interventions were included. The results revealed that rituximab was the most effective intervention for reducing MRSS (SMD = - 3.4, 95% CrI (- 4.2, - 2.7)), followed by cyclophosphamide (CTX) (SMD = - 2.8, (- 3.3, - 2.2)), and belimumab (SMD = - 1.5, (- 2.5, - 0.39)). Belimumab (SMD = 1.9, (0.75, 3.1)) and CTX (SMD = 1.3, (0.86, 1.8)) topped FVC improvement. Methotrexate (MTX) was the most effective for enhancing DLCO (SMD = 0.52, (0.046, 0.99)). Belimumab (HAQ: SMD = - 3.8, (- 5.5, - 2.1)) and CTX (HAQ: SMD = - 2.9, (- 3.4, - 2.3)) were significantly effective in lowering HAQ scores. B-cell-targeted therapies (e.g., rituximab and belimumab) seemed to outperform other therapeutic agents in lowering MRSS and HAQ scores. Conventional immunosuppressants (e.g., CTX and MTX) might be more effective in enhancing pulmonary functions. Treatment strategies should be tailored according to the extent and severity of organ involvement.
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