Evidence map›Paper›PMID 36031807›Full record

ArticleRheumatology (Oxford, England)2023

A data-driven approach finds RNA polymerase III antibody and tendon friction rubs as enrichment tools for early diffuse scleroderma trials.

Robyn T Domsic, Thomas A Medsger, Shiyao Gao, Maureen Laffoon, Suiyuan Huang, Stephen Wisniewski, Cathie Spino, Virginia Steen, Robert Lafyatis, Dinesh Khanna

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Rheumatology (Oxford, England), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.0field-weighted citation impact, top 24% of its field
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

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Article
  3. Recent Advances in Treatment of Systemic Sclerosis and Morphea.American journal of clinical dermatology · 2024
    Review
  4. Article
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

10 authors at 3 institutions in 1 country.

Robyn T DomsicDivision of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0002-2765-0922
Thomas A MedsgerDivision of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Shiyao GaoDepartment of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA.
Maureen LaffoonDivision of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Suiyuan HuangDivision of Rheumatology, Department of Internal Medicine and Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Stephen WisniewskiDepartment of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA.
Cathie SpinoDepartment of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Virginia SteenDivision of Rheumatology, Department of Medicine, Georgetown University, Washington, DC, USA.
Robert LafyatisDivision of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Dinesh KhannaDivision of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0003-1412-4453
University of Pittsburgh · USUniversity of Michigan · USGeorgetown University · US

Funding

Outcomes Research in Rheumatic DiseasesK24AR063120 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KHANNA, DINESH · 2012 to 2022
$1.6M
Addressing Critical Knowledge Gaps in Early Diffuse Scleroderma Trial DesignR01AR069874 · NIAMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DOMSIC, ROBYN THERESE · 2017 to 2020
$617k
NIAMS NIH HHS K24 AR063120NIAMS NIH HHS R01 AR069874
6 · The paper itself

Abstract

objectiveClinical trials in early diffuse SSc have consistently shown a placebo group response with a declining modified Rodnan skin score (mRSS), with negative outcomes. Our objective was to identify strategies using clinical characteristics or laboratory values to improve trial design.

methodsWe identified early diffuse SSc patients first seen at the University of Pittsburgh from 1980-2015. Eligible patients had ≥3 visits, with at least two mRSS scores within the first year of follow-up. We performed Kaplan-Meier analyses, group-based trajectory analysis of mRSS scores, followed by multivariable regression analysis and classification tree analysis. We applied the results to the abatacept in early diffuse systemic sclerosis (ASSET) trial outcome data.

resultsWe identified 403 patients with <18 months, and 514 with <36 months disease duration. The median number of mRSS follow-up scores was 14 (interquartile range 8, 25). All methodologic approaches identified skin thickness progression rate, RNA polymerase III (RNAP3) antibody positivity and presence of tendon friction rubs (TFR) as predictors of mRSS trajectory over 5 years of follow-up, and thereby as potential enrichment variables. When applied to the ASSET data, adjustment for both RNAP3 and TFR demonstrated reduction of the placebo mRSS response, particularly at 6 months. A significant difference in the ACR Composite Response Index in Systemic Sclerosis (CRISS) score was found with adjustment by RNAP3 at 6 months, and TFR or RNAP3 at 12 months.

conclusionAdjustment for both RNAP3 and TFR predicts mRSS trajectory and diminished the mRSS decline in ASSET placebo group, and identified significant differences in CRISS. RNAP3, particularly, is a stratification or enrichment approach to improve early diffuse SSc trial design.

Indexed as

Scleroderma, DiffuseScleroderma, SystemicFrictionHumansRNA Polymerase IIISeverity of Illness IndexSkinTendonsRNA Polymerase IIIclinical trial designearly diffuse sclerodermasclerodermaSSc

Identifiers

PMID36031807
PMCPMC10072884
OpenAlexW4293510897

What OpenQuestion holds

Textmetadata
Read underepoch 390

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 OpenQuestion graph.