Evidence map›Paper›PMID 41372962›Full record

Trial reportArthritis research & therapy2025

A composite biomarker score to predict modified Rodnan skin score in systemic sclerosis: insight from autologous stem cell transplantation international scleroderma trial.

Stefano Rodolfi, Kristina Clark, Bahja Ahmed Abdi, Elen Roblin, Medha Kanitkar, Voon H Ong, Alexandre E Voskuyl, Jeska K De Vries-Bouwstra, Jacob M van Laar, Christopher P Denton and 1 more

Abstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Arthritis research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from 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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Stefano RodolfiDivision of Medicine, Department of Inflammation, Centre for Rheumatology and Connective Tissue Diseases, Royal Free and University College Medical School, University College London, London, UK. s.rodolfi@ucl.ac.uk.
Kristina ClarkDivision of Medicine, Department of Inflammation, Centre for Rheumatology and Connective Tissue Diseases, Royal Free and University College Medical School, University College London, London, UK.
Bahja Ahmed AbdiDivision of Medicine, Department of Inflammation, Centre for Rheumatology and Connective Tissue Diseases, Royal Free and University College Medical School, University College London, London, UK.
Elen RoblinDivision of Medicine, Department of Inflammation, Centre for Rheumatology and Connective Tissue Diseases, Royal Free and University College Medical School, University College London, London, UK.
Medha KanitkarDivision of Medicine, Department of Inflammation, Centre for Rheumatology and Connective Tissue Diseases, Royal Free and University College Medical School, University College London, London, UK.
Voon H OngDivision of Medicine, Department of Inflammation, Centre for Rheumatology and Connective Tissue Diseases, Royal Free and University College Medical School, University College London, London, UK.
Alexandre E VoskuylDepartment of Rheumatology and Clinical Immunology, Amsterdam University Medical Centre, Amsterdam, The Netherlands.
Jeska K De Vries-BouwstraDepartment of Rheumatology, Leiden University Medical Centre, Leiden, Netherlands.
Jacob M van LaarDepartment of Rheumatology & Clinical Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.
Christopher P DentonDivision of Medicine, Department of Inflammation, Centre for Rheumatology and Connective Tissue Diseases, Royal Free and University College Medical School, University College London, London, UK.
Julia SpieringsDivision of Medicine, Department of Inflammation, Centre for Rheumatology and Connective Tissue Diseases, Royal Free and University College Medical School, University College London, London, UK.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSkin fibrosis is a cardinal manifestation of systemic sclerosis (SSc) and is routinely measured by modified Rodnan skin score (mRSS), which is however limited by its operator-dependence and may not reflect the complex disease biology at the cutaneous compartment. A recent high dimensional multi-omic analysis identified 3 serum proteins independently associated with mRSS: tenascin C (TENC), cartilage oligomeric matrix protein (COMP), and collagen type IV alpha 1 (COL4A1). The aim of our study was to evaluate the relationship between these analytes as cross-sectional and dynamic biomarkers for skin involvement, as well as to capture potential correlations with type of immunosuppressive treatment.

methodsWe selected 21 patients from 2 Dutch centres who participated in the Autologous Stem Cell Transplantation International Scleroderma trial - a phase 3, multicentre, randomized study comparing autologous stem cell transplantation (HSCT) to cyclophosphamide (CYC) in diffuse cutaneous (dc)SSc. Serum concentrations of the three analytes were measured with ELISAs at baseline, 12 and 24 months. We employed linear mixed-effects models to assess cross-sectional correlation between mRSS, analyte concentrations and time. A multivariable linear regression model (independent of time) was used to formulate a composite biomarker score to predict mRSS.

resultsThere were 11 patients in the CYC arm, and 10 to the HSCT arm. Serum concentrations of COMP and COL4A1, but not TENC, showed significant correlation with mRSS at the mixed model; COL4A1 correlation with mRSS remained significant at multivariable analysis (β = 0.01, p = 0.001). We derived a composite biomarker formula score to predict mRSS with good performance at Bland Altman plot. As dynamic biomarkers, only changes in concentrations of COMP were associated with mRSS change (r = 0.013; p = 0.012). It is notable that there was greater reduction in COL4A1 concentration at 24 months in the HSCT group compared with CYC (-81 ng/mL vs. -27.4 ng/mL in CYC group; p = 0.029).

conclusionOur composite biomarker score showed a moderate cross-sectional correlation with mRSS and potentially complement mRSS in the assessment of skin activity. The differential variations for serum COL4A1 across treatment groups warrant further evaluation as a predictive marker of immunotherapeutic response in dcSSc.

Indexed as

BiomarkersScleroderma, SystemicSkinStem Cell TransplantationAdultCartilage Oligomeric Matrix ProteinCollagen Type IVCross-Sectional StudiesFemaleHematopoietic Stem Cell TransplantationHumansImmunosuppressive AgentsMaleMiddle AgedSeverity of Illness IndexTenascinBiomarkersCartilage Oligomeric Matrix ProteinCollagen Type IVImmunosuppressive AgentsTenascinTSP5 protein, humanBiomarkerCyclophosphamideDiffuse cutaneous systemic sclerosisModified rodnan skin scoreSkin fibrosisStem cell transplantationSystemic sclerosis

Identifiers

PMID41372962
PMCPMC12801594

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

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.