Evidence map›Paper›PMID 38199849›Full record

Trial reportRMD open2024

Identification of patient endotypes and adalimumab treatment responders in axial spondyloarthritis using blood-derived extracellular matrix biomarkers.

Helena Port, Frederik Christiansen, Signe Holm Nielsen, Peder Frederiksen, Anne-C Bay-Jensen, Morten Asser Karsdal, Sengul Seven, Inge Juul Sørensen, Anne Gitte Loft, Ole Rintek Madsen and 2 more

Open access · goldAbstract readRandomized Controlled TrialMulticenter Study
In one paragraph

Trial report in RMD open, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.5field-weighted citation impact, top 40% 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

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. Review
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

12 authors at 5 institutions in 2 countries.

Helena PortDepartment of Clinical Medicine, Copenhagen University Hospital, Kobenhavn, Denmark hep@nordicbio.com.ORCID 0000-0002-9716-572X
Frederik ChristiansenNordic Bioscience, Herlev, Denmark.
Signe Holm NielsenNordic Bioscience, Herlev, Denmark.
Peder FrederiksenNordic Bioscience, Herlev, Denmark.
Anne-C Bay-JensenNordic Bioscience, Herlev, Denmark.
Morten Asser KarsdalNordic Bioscience, Herlev, Denmark.
Sengul SevenCopenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Gentofte and Frederiksberg, Denmark.
Inge Juul SørensenDepartment of Clinical Medicine, Copenhagen University Hospital, Kobenhavn, Denmark.
Anne Gitte LoftDepartment of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.
Ole Rintek MadsenDepartment of Clinical Medicine, Copenhagen University Hospital, Kobenhavn, Denmark.
Mikkel OstergaardDepartment of Clinical Medicine, Copenhagen University Hospital, Kobenhavn, Denmark.
Susanne J PedersenCopenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Gentofte and Frederiksberg, Denmark.
Nordic Bioscience (Denmark) · DKCopenhagen University Hospital · DKAarhus University Hospital · DKCenter for Rheumatology · USRigshospitalet · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo explore the potential of a panel of ECM remodelling markers as endotyping tools for axial spondyloarthritis (axSpA) by separating patients into subtypes and investigate how they differ among each other in disease activity scores and response to treatment with adalimumab.

methodsIn three axSpA studies, a panel of 14 blood-based ECM biomarkers related to formation of collagen (PRO-C2, PRO-C3, PRO-C6), degradation of collagen by metalloproteinases (C1M, C2M, T2CM, C3M, C4M, C6M, C10C), matrix metalloproteinase (MMP)-degraded prolargin (PROM), MMP-degraded and citrullinated vimentin (VICM), basement membrane turnover (PRO-C4) and neutrophil activity (CPa9-HNE) were assessed to enable patient clustering (endotyping). MASH (n=41) was a cross-sectional study, while Adalimumab in Axial Spondyloarthritis study (ASIM,n=45) and Danish Multicenter Study of Adalimumab in Spondyloarthritis (DANISH, n=49) were randomised, double-blind placebo-controlled trials of adalimumab versus placebo every other week for 6 or 12 weeks, respectively, followed by active treatment. Biomarker data were log-transformed, standardised by mean centering and scaled by the SD prior to principal component analysis and K-means clustering.

resultsBased on all three studies, we identified two orthogonal dimensions reflecting: (1) inflammation and neutrophil activity (driven by C1M and CPa9-HNE) and (2) collagen turnover (driven by PRO-C2). Three endotypes were identified: high inflammation endotype (Endotype1), low inflammation endotype (Endotype 2) and high collagen turnover endotype (Endotype3). Endotype1 showed higher disease activity (Ankylosing Spondylitis Disease Activity Score (ASDAS)) at baseline compared with Endotype2 and Endotype3 and higher percentage of patients responding to adalimumab based on ASDAS clinical improvement at week 24. Endotype3 showed higher percentage of patients with 50% improvement in Bath Ankylosing Spondylitis Disease Activity Index response at week 24 compared with Endotype2.

conclusionThese endotypes differ in their tissue remodelling profile and may in the future have utility for patient stratification and treatment tailoring.

Indexed as

Axial SpondyloarthritisSpondylitis, AnkylosingAdalimumabBiomarkersCross-Sectional StudiesExtracellular MatrixHumansInflammationAdalimumabBiomarkersAdalimumabChondrocytesSpondylitis, Ankylosing

Identifiers

PMID38199849
PMCPMC10806480
OpenAlexW4390718391

What OpenQuestion holds

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LicenceCC BY-NC
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.