Trial reportAnnals of the rheumatic diseases2018
Therapeutic interleukin-6 blockade reverses transforming growth factor-beta pathway activation in dermal fibroblasts: insights from the faSScinate clinical trial in systemic sclerosis.
Trial report in Annals of the rheumatic diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01532869 (A Phase II/III, Multicenter, Randomized, Double-blind, Placebo-controlled Study To Assess The Efficacy And Safety Of Tocilizumab Versus Placebo In Patients With Systemic Sclerosis), which is not on this map. Cited by 92 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase II/III, Multicenter, Randomized, Double-blind, Placebo-controlled Study To Assess The Efficacy And Safety Of Tocilizumab Versus Placebo In Patients With Systemic Sclerosis
Who cites it
92 citing papers in PubMed, 2 syntheses or guidelines pooled it, 159 citations in OpenAlex.
- Efficacy of different pharmacological therapies for diffuse cutaneous systemic sclerosis: a systematic review and network meta-analysis.European journal of clinical pharmacology · 2026Pooled it
- Impact of Innovative Treatment Using Biological Drugs for the Modulation of Diffuse Cutaneous Systemic Sclerosis: A Systematic Review.Medicina (Kaunas, Lithuania) · 2023Pooled it
- Biological and clinical insights from a randomized phase 2 study of an anti-oncostatin M monoclonal antibody in systemic sclerosis.Rheumatology (Oxford, England) · 2022Trial
- Tocilizumab Prevents Progression of Early Systemic Sclerosis-Associated Interstitial Lung Disease.Arthritis & rheumatology (Hoboken, N.J.) · 2021Trial
- Article
- Soluble CD13 in systemic sclerosis: clinical observations and transcriptomic insights from peripheral blood.Arthritis research & therapy · 2026Article
- Article
- Pyruvate kinase M2 is elevated in systemic sclerosis and plays a role in its pathogenesis.Frontiers in immunology · 2026Article
- The immune landscape of systemic sclerosis: from pathogenic mechanisms to precision therapeutic breakthroughs.Frontiers in immunology · 2026Review
- Systemic sclerosis: pathogenic mechanisms and their implications for treatment.Seminars in immunopathology · 2025Review
- Advances in the Molecular Mechanisms of Pulmonary Fibrosis in Systemic Sclerosis: A Comprehensive Review.International journal of molecular sciences · 2025Review
- Characterization of a pathogenic nonmigratory fibroblast population in systemic sclerosis skin.JCI insight · 2025Article
- Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- Cell autonomous TLR4 signaling modulates TGF-β induced activation of human cardiac fibroblasts.Heliyon · 2025Article
- Breaking the cycle: should we target inflammation, fibrosis, or both?Frontiers in immunology · 2025Review
- Vimentin immunization induces TH2/TH17 cell activation and autoantibody production in a novel mouse model of bleomycin induced systemic sclerosis.Frontiers in immunology · 2025Article
- ADAM Metallopeptidase domain 19 promotes skin fibrosis in systemic sclerosis via neuregulin-1.Molecular medicine (Cambridge, Mass.) · 2024Article
- Tocilizumab plus Nintedanib for progressive interstitial lung disease in systemic sclerosis: a one-year observational study.Rheumatology international · 2024Observational
- Pathogenesis of interstitial lung disease in systemic sclerosis.Rheumatology and immunology research · 2024Article
- Orofacial Complications of the Connective Tissue Disease Systemic Sclerosis.Journal of dental research · 2024Review
32 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesSkin fibrosis mediated by activated dermal fibroblasts is a hallmark of systemic sclerosis (SSc), especially in the subset of patients with diffuse disease. Transforming growth factor-beta (TGFβ) and interleukin-6 (IL-6) are key candidate mediators in SSc. Our aim was to elucidate the specific effect of IL-6 pathway blockade on the biology of SSc fibroblasts in vivo by using samples from a unique clinical experiment-the faSScinate study-in which patients with SSc were treated for 24 weeks with tocilizumab (TCZ), an IL-6 receptor-α inhibitor.
methodsWe analysed the molecular, functional and genomic characteristics of explant fibroblasts cultured from matched skin biopsy samples collected at baseline and at week 24 from 12 patients receiving placebo (n=6) or TCZ (n=6) and compared these with matched healthy control fibroblast strains.
resultsThe hallmark functional and molecular-activated phenotype was defined in SSc samples and was stable over 24 weeks in placebo-treated cases. RNA sequencing analysis robustly defined key dysregulated pathways likely to drive SSc fibroblast activation in vivo. Treatment with TCZ for 24 weeks profoundly altered the biological characteristics of explant dermal fibroblasts by normalising functional properties and reversing gene expression profiles dominated by TGFβ-regulated genes and molecular pathways.
conclusionsWe demonstrated the exceptional value of using explant dermal fibroblast cultures from a well-designed trial in SSc to provide a molecular framework linking IL-6 to key profibrotic pathways. The profound impact of IL-6R blockade on the activated fibroblast phenotype highlights the potential of IL-6 as a therapeutic target in SSc and other fibrotic diseases. TRIAL REGISTRATION NUMBER: NCT01532869; Post-results.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.