Trial reportThe Journal of clinical investigation2015
Fresolimumab treatment decreases biomarkers and improves clinical symptoms in systemic sclerosis patients.
Trial report in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01284322 (OPEN LABEL TRIAL OF ANTI-TGF-BETA MAB, FRESOLIMUMAB, IN SYSTEMIC SCLEROSIS - A PHASE ONE BIOMARKER TRIAL), which is not on this map. Cited by 195 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Open label trial of anti-tgf-beta mab, fresolimumab, in systemic sclerosis - a phase one biomarker trial
Who cites it
195 citing papers in PubMed, 2 syntheses or guidelines pooled it, 337 citations in OpenAlex.
- Engineered antigen-specific regulatory T cells for autoimmune skin conditions.Autoimmunity reviews · 2021Pooled it
- A Functional Genomic Meta-Analysis of Clinical Trials in Systemic Sclerosis: Toward Precision Medicine and Combination Therapy.The Journal of investigative dermatology · 2017Pooled it
- Biomarker analysis from the phase 2b randomized placebo-controlled trial of riociguat in early diffuse cutaneous systemic sclerosis.Rheumatology (Oxford, England) · 2024Trial
- Biological and clinical insights from a randomized phase 2 study of an anti-oncostatin M monoclonal antibody in systemic sclerosis.Rheumatology (Oxford, England) · 2022Trial
- Inhibition of β-Catenin Signaling in the Skin Rescues Cutaneous Adipogenesis in Systemic Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Trial of C-82.The Journal of investigative dermatology · 2017Trial
- Mathematical Modeling of Systemic Sclerosis and Its Treatment.Bulletin of mathematical biology · 2026Article
- The inflammatory/fibrotic axis across organs: myelofibrosis as a model of reversibility.JCI insight · 2026Review
- Altered AP-1, RUNX, and EGR chromatin dynamics drive human fibrotic lung disease.Annals of the rheumatic diseases · 2026Article
- Erectile dysfunction and Peyronie's disease: from biologics to nanomedicine-enabled therapies.Sexual medicine · 2026Review
- Article
- Pumping Up Dermatologic Drug Reformulation: A Review of How Proton Pump Inhibitors May Revolutionize Scleroderma Treatment.The Journal of clinical and aesthetic dermatology · 2026Review
- RUNX1 is expressed in a subpopulation of dermal fibroblasts and is associated with disease severity of systemic sclerosis.Annals of the rheumatic diseases · 2026Article
- Research Advances in Therapeutic Strategies and Drug Delivery Systems for Pathological Scars.Pharmaceutics · 2026Review
- The role of thrombospondin-1 in dermatological conditions.Frontiers in medicine · 2026Review
- A Narrative Review of Salivary Gland Extracellular Matrix and Sjögren's Syndrome: Research Status and Future Prospects.Biomolecules · 2026Review
- Nanomedicine-Driven Modulation of Signaling Pathways in Hepatic Fibrosis.International journal of nanomedicine · 2026Review
- Immunologic Combinations in Multiple Myeloma: Synergistic Stimulation with T cells and NK cells.International journal of biological sciences · 2026Review
- Radiation-Induced Fibrosis (RIF) in Head and Neck Squamous Cell Carcinoma (HNSCC): A Review.Cells · 2025Review
- Endothelial-to-Mesenchymal Transition in Health and Disease: Molecular Insights and Therapeutic Implications.International journal of molecular sciences · 2025Review
- Concentrated Micronized Fat Ameliorates Skin Fibrosis in Bleomycin-Induced Murine Model and Enhances Fat Graft Survival.Aesthetic plastic surgery · 2025Article
135 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
16 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundTGF-β has potent profibrotic activity in vitro and has long been implicated in systemic sclerosis (SSc), as expression of TGF-β-regulated genes is increased in the skin and lungs of patients with SSc. Therefore, inhibition of TGF-β may benefit these patients.
methodsPatients with early, diffuse cutaneous SSc were enrolled in an open-label trial of fresolimumab, a high-affinity neutralizing antibody that targets all 3 TGF-β isoforms. Seven patients received two 1 mg/kg doses of fresolimumab, and eight patients received one 5 mg/kg dose of fresolimumab. Serial mid-forearm skin biopsies, performed before and after treatment, were analyzed for expression of the TGF-β-regulated biomarker genes thrombospondin-1 (THBS1) and cartilage oligomeric protein (COMP) and stained for myofibroblasts. Clinical skin disease was assessed using the modified Rodnan skin score (MRSS).
resultsIn patient skin, THBS1 expression rapidly declined after fresolimumab treatment in both groups (P = 0.0313 at 7 weeks and P = 0.0156 at 3 weeks), and skin expression of COMP exhibited a strong downward trend in both groups. Clinical skin disease dramatically and rapidly decreased (P < 0.001 at all time points). Expression levels of other TGF-β-regulated genes, including SERPINE1 and CTGF, declined (P = 0.049 and P = 0.012, respectively), and a 2-gene, longitudinal pharmacodynamic biomarker of SSc skin disease decreased after fresolimumab treatment (P = 0.0067). Dermal myofibroblast infiltration also declined in patient skin after fresolimumab (P < 0.05). Baseline levels of THBS1 were predictive of reduced THBS1 expression and improved MRSS after fresolimumab treatment.
conclusionThe rapid inhibition of TGF-β-regulated gene expression in response to fresolimumab strongly implicates TGF-β in the pathogenesis of fibrosis in SSc. Parallel improvement in the MRSS indicates that fresolimumab rapidly reverses markers of skin fibrosis.
trial registrationClinicaltrials.gov NCT01284322.
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What Socratic holds
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 Socratic graph.