Evidence map›Paper›PMID 38918871›Full record

Trial reportArthritis research & therapy2024

S100 proteins as potential predictive biomarkers of abatacept response in polyarticular juvenile idiopathic arthritis.

Hermine I Brunner, Grant S Schulert, Alyssa Sproles, Sherry Thornton, Gabriel Vega Cornejo, Jordi Antón, Ruben Cuttica, Michael Henrickson, Ivan Foeldvari, Daniel J Kingsbury and 9 more

Erratum issued Registry-linked trialAbstract readClinical Trial, Phase IIIRandomized Controlled Trial
In one paragraph

Trial report in Arthritis research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT01844518 (A Phase 3 Multi-center, Open-Label Study to Evaluate Pharmacokinetics, Efficacy and Safety of Abatacept Administered Subcutaneously), which is not on this map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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.

NCT01844518 phase3completednot on this map

A Phase 3 Multi-center, Open-Label Study to Evaluate Pharmacokinetics, Efficacy and Safety of Abatacept Administered Subcutaneously (SC) in Children and Adolescents With Active Polyarticular Juvenile Idiopathic Arthritis (pJIA) and Inadequate Response (IR) to Biologic or Non Biologic Disease Modifying Anti-rheumatic Drugs (DMARDs)

TypeinterventionalSponsorBristol-Myers SquibbRan2013 to 2023Enrolled219ConditionsActive Polyarticular Juvenile Idiopathic ArthritisArmsAbatacept
3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Hermine I BrunnerDivision of Rheumatology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA. Hermine.brunner@cchmc.org.
Grant S SchulertDivision of Rheumatology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Alyssa SprolesDivision of Rheumatology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Sherry ThorntonDivision of Rheumatology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Gabriel Vega CornejoHospital México Americano, Guadalajara, CREA, Mexico.
Jordi AntónPediatric Rheumatology Department, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain.
Ruben CutticaRuben Cuttica MD, Pediatric Rheumatology, Hospital General de Niños Pedro de Elizalde, Buenos Aires, Argentina.
Michael HenricksonDivision of Rheumatology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Ivan FoeldvariHamburg Centre for Pediatric and Adolescent Rheumatology, Schön Klinik Hamburg Eilbek, Hamburg, Germany.
Daniel J KingsburyDivision of Rheumatology, Randall Children's Hospital at Legacy Emanuel, Portland, OR, USA.
Margarita AskelsonGlobal Biometric Sciences, Bristol Myers Squibb, Princeton, NJ, USA.
Jinqi LiuTranslational Medicine, Bristol Myers Squibb, Princeton, NJ, USA.
Sumanta MukherjeeTranslational Medicine, Bristol Myers Squibb, Princeton, NJ, USA.
Robert L WongBristol Myers Squibb, Immunology and Fibrosis, Princeton, NJ, USA.
Daniel J LovellDivision of Rheumatology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Alberto MartiniDipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DiNOGMI), Università degli Studi di Genova, Genoa, Italy.
Nicolino RupertoIRCCS Istituto Giannina Gaslini, Gaslini Trial Centre/Servizio di Sperimentazioni Cliniche Pediatriche, PRINTO, Genoa, Italy.
Alexei A GromDivision of Rheumatology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Pediatric Rheumatology Collaborative Study Group (PRCSG) and the Paediatric Rheumatology International Trials Organisation (PRINTO)

Funding

Tissue Repository CoreP30AR070549 · NIAMS · CINCINNATI CHILDRENS HOSP MED CTR · PI Grant Sanford Schulert · 2016 to 2026
$7.7M
Pediatric musculOskeletal & RheumaTology Innovation COre center (PORTICO)P30AR076316 · NIAMS · CINCINNATI CHILDRENS HOSP MED CTR · PI BRUNNER, HERMINE I · 2019 to 2023
$3.4M
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health (NIH) P30 AR076316 and P30 AR070549NIAMS NIH HHS P30 AR070549NIAMS NIH HHS P30 AR076316
6 · The paper itself

Abstract

backgroundJuvenile idiopathic arthritis (JIA) comprises a heterogeneous group of conditions that can cause marked disability and diminished quality of life. Data on predictors of clinical response are insufficient to guide selection of the appropriate biologic agent for individual patients. This study aimed to investigate the propensity of S100A8/9 and S100A12 as predictive biomarkers of abatacept response in polyarticular-course juvenile idiopathic arthritis (pJIA).

methodsData from a phase 3 trial (NCT01844518) of subcutaneous abatacept in patients with active pJIA (n = 219) were used in this exploratory analysis. Association between biomarker levels at baseline and improvements in JIA-American College of Rheumatology (ACR) criteria responses or baseline disease activity (measured by Juvenile Arthritis Disease Activity Score in 27 joints using C-reactive protein [JADAS27-CRP]) were assessed. Biomarker level changes from baseline to month 4 were assessed for disease outcome prediction up to 21 months.

resultsAt baseline, 158 patients had available biomarker samples. Lower baseline S100A8/9 levels (≤ 3295 ng/mL) were associated with greater odds of achieving JIA-ACR90 (odds ratio [OR]: 2.54 [95% confidence interval (CI): 1.25-5.18]), JIA-ACR100 (OR: 3.72 [95% CI: 1.48-9.37]), JIA-ACR inactive disease (ID; OR: 4.25 [95% CI: 2.03-8.92]), JADAS27-CRP ID (OR: 2.34 [95% CI: 1.02-5.39]) at month 4, and JIA-ACR ID (OR: 3.01 [95% CI: 1.57-5.78]) at month 16. Lower baseline S100A12 levels (≤ 176 ng/mL) were associated with greater odds of achieving JIA-ACR90 (OR: 2.52 [95% CI: 1.23-5.13]), JIA-ACR100 (OR: 3.68 [95% CI: 1.46-9.28]), JIA-ACR ID (OR: 3.66 [95% CI: 1.76-7.61]), JIA-ACR90 (OR: 2.03 [95% CI: 1.07-3.87]), JIA-ACR100 (OR: 2.14 [95% CI: 1.10-4.17]), and JIA-ACR ID (OR: 4.22 [95% CI: 2.15-8.29]) at month 16. From baseline to month 4, decreases in S100A8/9 and S100A12 generally exceeded 50% among JIA-ACR90/100/ID responders.

conclusionLower baseline levels of S100A8/9 and S100A12 proteins predicted better response to abatacept treatment than higher levels and may serve as early predictive biomarkers in pJIA. Decreases in these biomarker levels may also predict longer-term response to abatacept in pJIA.

Indexed as

AbataceptAntirheumatic AgentsArthritis, JuvenileBiomarkersAdolescentCalgranulin ACalgranulin BChildChild, PreschoolFemaleHumansMaleS100A12 ProteinS100 ProteinsTreatment OutcomeAbataceptAntirheumatic AgentsBiomarkersCalgranulin ACalgranulin BS100A12 ProteinS100A12 protein, humanS100A8 protein, humanS100A9 protein, humanS100 ProteinsAbataceptBiomarkersC-Reactive protein (CRP)Juvenile idiopathic arthritisS100

Identifiers

PMID38918871
PMCPMC11197242

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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.