{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T03:39:19Z","timestamp":1793417959852,"version":"4.5.0"},"reference-count":21,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T00:00:00Z","timestamp":1704844800000},"content-version":"unspecified","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012774","name":"Innovation Fund Denmark","doi-asserted-by":"crossref","award":["0153\u201100086B"],"award-info":[{"award-number":["0153\u201100086B"]}],"id":[{"id":"10.13039\/100012774","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2023,12,18]]},"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Based 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>These endotypes differ in their tissue remodelling profile and may in the future have utility for patient stratification and treatment tailoring.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/rmdopen-2023-003769","type":"journal-article","created":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T21:21:13Z","timestamp":1704921673000},"page":"e003769","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Identification of patient endotypes and adalimumab treatment responders in axial spondyloarthritis using blood-derived extracellular matrix biomarkers"],"prefix":"10.1136","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9716-572X","authenticated-orcid":false,"given":"Helena","family":"Port","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine, Copenhagen University Hospital, Kobenhavn, Denmark"},{"name":"Nordic Bioscience, Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik","family":"Christiansen","sequence":"additional","affiliation":[{"name":"Nordic Bioscience, Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Signe Holm","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Nordic Bioscience, Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peder","family":"Frederiksen","sequence":"additional","affiliation":[{"name":"Nordic Bioscience, Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-C","family":"Bay-Jensen","sequence":"additional","affiliation":[{"name":"Nordic Bioscience, Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten Asser","family":"Karsdal","sequence":"additional","affiliation":[{"name":"Nordic Bioscience, Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sengul","family":"Seven","sequence":"additional","affiliation":[{"name":"Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Gentofte and Frederiksberg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge Juul","family":"S\u00f8rensen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Copenhagen University Hospital, Kobenhavn, Denmark"},{"name":"Department of Rheumatology and Spine diseases, Righospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Gitte","family":"Loft","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole Rintek","family":"Madsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Copenhagen University Hospital, Kobenhavn, Denmark"},{"name":"Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Gentofte and Frederiksberg, Denmark"},{"name":"Department of Rheumatology and Spine diseases, Righospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikkel","family":"Ostergaard","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Copenhagen University Hospital, Kobenhavn, Denmark"},{"name":"Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Gentofte and Frederiksberg, Denmark"},{"name":"Department of Rheumatology and Spine diseases, Righospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne J","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Gentofte and Frederiksberg, Denmark"},{"name":"Department of Rheumatology and Spine diseases, Righospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2024,1,10]]},"reference":[{"key":"2025090313281614000_10.1.e003769.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31591-4"},{"key":"2025090313281614000_10.1.e003769.2","doi-asserted-by":"crossref","DOI":"10.1186\/s13075-022-02839-1","article-title":"Extracellular matrix protein turnover markers are associated with axial Spondyloarthritis\u2014a comparison with postpartum women and other 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A glance into the future of diagnosis and treatment Ofspondyloarthritis. Ther Adv Musculoskelet Dis 2022;14. doi:10.1177\/1759720X221111611","DOI":"10.1177\/1759720X221111611"},{"key":"2025090313281614000_10.1.e003769.7","doi-asserted-by":"crossref","first-page":"3289","DOI":"10.1093\/rheumatology\/keab873","article-title":"Cluster analysis in early axial Spondyloarthritis predicts poor outcome in the presence of peripheral Articular manifestations","volume":"61","author":"Costantino","year":"2022","journal-title":"Rheumatology (Oxford)"},{"key":"2025090313281614000_10.1.e003769.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.11.037"},{"key":"2025090313281614000_10.1.e003769.9","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61452-X"},{"key":"2025090313281614000_10.1.e003769.10","doi-asserted-by":"crossref","unstructured":"Holm Nielsen S , Sun S , Bay-Jensen AC , et al . 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