{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T20:13:49Z","timestamp":1776456829728,"version":"3.51.2"},"reference-count":43,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T00:00:00Z","timestamp":1672358400000},"content-version":"unspecified","delay-in-days":29,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Bristol Myers Squibb"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2022,12,7]]},"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To investigate correlations between biomarkers of bone remodelling and extracellular matrix turnover with baseline disease activity and treatment response in patients with early rheumatoid arthritis (RA).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                     <jats:underline>A<\/jats:underline>ssessing <jats:underline>V<\/jats:underline>ery <jats:underline>E<\/jats:underline>arly <jats:underline>R<\/jats:underline>heumatoid arthritis <jats:underline>T<\/jats:underline>reatment-2 (AVERT-2; <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT02504268\">NCT02504268<\/jats:ext-link>) included disease-modifying antirheumatic drug-naive, anti-citrullinated protein antibody (ACPA)-positive patients randomised to weekly subcutaneous abatacept+methotrexate (MTX) or abatacept placebo+MTX for 56 weeks. This post hoc exploratory subanalysis assessed the association between baseline disease activity and eight biomarkers (Spearman\u2019s correlation coefficient), and whether baseline biomarkers (continuous or categorical variables) could predict treatment response at weeks 24 and 52 (logistic regression).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Patient characteristics were similar between overall (n=752) and biomarker subgroup (n=535) populations and across treatments. At baseline, neoepitopes of matrix metalloproteinase-mediated degradation products of types III and IV collagen and of C reactive protein (CRP) showed the greatest correlations with disease activity; cross-linked carboxy-terminal telopeptide of type I collagen (CTX-I) showed weak correlation. Only CTX-I predicted treatment response; baseline CTX-I levels were significantly associated with achieving Simplified Disease Activity Index remission and Disease Activity Score in 28 joints (DAS28 (CRP)) &lt;2.6 (weeks 24 and 52), and American College of Rheumatology 70 response (week 52), in patients treated with abatacept+MTX\u2009but not abatacept placebo+MTX. CTX-I predicted significant differential response between arms for DAS28 (CRP) &lt;2.6 (week 24). Treatment differences were greater for abatacept+MTX in patients with medium\/high versus low baseline CTX-I.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>In MTX-naive, ACPA-positive patients with early RA, baseline CTX-I predicted treatment response to abatacept+MTX\u2009but not abatacept placebo+MTX.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/rmdopen-2022-002683","type":"journal-article","created":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T09:46:01Z","timestamp":1672393561000},"page":"e002683","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Baseline serum levels of cross-linked carboxy-terminal telopeptide of type I collagen predict abatacept treatment response in methotrexate-naive, anticitrullinated protein antibody-positive patients with early rheumatoid arthritis"],"prefix":"10.1136","volume":"8","clinical-trial-number":[{"clinical-trial-number":"nct02504268","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02504268","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02504268","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct00106535","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01197521","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Chun","family":"Wu","sequence":"first","affiliation":[{"name":"Bristol Myers Squibb, Princeton, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanhua","family":"Hu","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, Princeton, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Schafer","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, Princeton, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean E","family":"Connolly","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, Princeton, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Wong","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, Princeton, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Signe Holm","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Nordic Bioscience, Herlev, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne-Christine","family":"Bay-Jensen","sequence":"additional","affiliation":[{"name":"Nordic Bioscience, Herlev, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7429-8482","authenticated-orcid":false,"given":"Paul","family":"Emery","sequence":"additional","affiliation":[{"name":"University of Leeds and Leeds NIHR Biomedical Research Centre, Leeds, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0807-7139","authenticated-orcid":false,"given":"Yoshiya","family":"Tanaka","sequence":"additional","affiliation":[{"name":"University of Occupational and Environmental Health, Kitakyushu, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1219-3845","authenticated-orcid":false,"given":"Vivian P","family":"Bykerk","sequence":"additional","affiliation":[{"name":"Hospital for Special Surgery, New York, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clifton O","family":"Bingham","sequence":"additional","affiliation":[{"name":"Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7033-7520","authenticated-orcid":false,"given":"Thomas WJ","family":"Huizinga","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center, Leiden, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6630-1477","authenticated-orcid":false,"given":"Roy","family":"Fleischmann","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center, Metroplex Clinical Research Center, Dallas, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0094-9801","authenticated-orcid":false,"given":"Jinqi","family":"Liu","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, Princeton, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2022,12,30]]},"reference":[{"key":"2025090312090271000_8.2.e002683.1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.13103"},{"key":"2025090312090271000_8.2.e002683.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1004965"},{"key":"2025090312090271000_8.2.e002683.3","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2015.171"},{"key":"2025090312090271000_8.2.e002683.4","doi-asserted-by":"crossref","first-page":"18001","DOI":"10.1038\/nrdp.2018.1","article-title":"Rheumatoid arthritis","volume":"4","author":"Smolen","year":"2018","journal-title":"Nat Rev Dis Primers"},{"key":"2025090312090271000_8.2.e002683.5","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2019-216655"},{"key":"2025090312090271000_8.2.e002683.6","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1002\/art.41752","article-title":"2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis","volume":"73","author":"Fraenkel","year":"2021","journal-title":"Arthritis Rheumatol"},{"key":"2025090312090271000_8.2.e002683.7","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-205428"},{"key":"2025090312090271000_8.2.e002683.8","doi-asserted-by":"publisher","DOI":"10.1186\/ar1767"},{"key":"2025090312090271000_8.2.e002683.9","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.170007"},{"key":"2025090312090271000_8.2.e002683.10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0089442"},{"key":"2025090312090271000_8.2.e002683.11","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s40744-021-00401-0","article-title":"Baseline anti-citrullinated protein antibody status and response to abatacept or non-TNFi biologic\/targeted-synthetic DMARDs: US observational study of patients with RA","volume":"9","author":"Harrold","year":"2022","journal-title":"Rheumatol Ther"},{"key":"2025090312090271000_8.2.e002683.12","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2015-207942"},{"key":"2025090312090271000_8.2.e002683.13","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-202958"},{"key":"2025090312090271000_8.2.e002683.14","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ker435"},{"key":"2025090312090271000_8.2.e002683.15","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0219980","article-title":"Identification of pathological RA endotypes using blood-based biomarkers reflecting tissue metabolism. A retrospective and explorative analysis of two phase III RA studies","volume":"14","author":"Blair","year":"2019","journal-title":"PLoS One"},{"key":"2025090312090271000_8.2.e002683.16","first-page":"462","article-title":"Increased remodelling of interstitial collagens and basement membrane is suppressed by treatment in patients with rheumatoid arthritis: serological evaluation of a one-year prospective study of 149 Japanese patients","volume":"36","author":"Gudmann","year":"2018","journal-title":"Clin Exp Rheumatol"},{"key":"2025090312090271000_8.2.e002683.17","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.3390\/jcm10132905","article-title":"Bone metabolism and RANKL\/OPG ratio in rheumatoid arthritis women treated with TNF-\u03b1 inhibitors","volume":"10","author":"Jura-P\u00f3\u0142torak","year":"2021","journal-title":"J Clin Med"},{"key":"2025090312090271000_8.2.e002683.18","doi-asserted-by":"crossref","first-page":"484280","DOI":"10.1155\/2014\/484280","article-title":"Bone remodelling markers in rheumatoid arthritis","volume":"2014","author":"Fardellone","year":"2014","journal-title":"Mediators Inflamm"},{"key":"2025090312090271000_8.2.e002683.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2010.03.012"},{"key":"2025090312090271000_8.2.e002683.20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0054504"},{"key":"2025090312090271000_8.2.e002683.21","first-page":"653","article-title":"Type I and III collagen turnover is increased in axial spondyloarthritis and psoriatic arthritis. Associations with disease activity and diagnostic capacity","volume":"35","author":"Gudmann","year":"2017","journal-title":"Clin Exp Rheumatol"},{"key":"2025090312090271000_8.2.e002683.22","doi-asserted-by":"publisher","DOI":"10.3109\/1354750X.2011.620628"},{"key":"2025090312090271000_8.2.e002683.23","doi-asserted-by":"publisher","DOI":"10.1186\/ar4266"},{"key":"2025090312090271000_8.2.e002683.24","doi-asserted-by":"publisher","DOI":"10.1186\/1755-1536-4-22"},{"key":"2025090312090271000_8.2.e002683.25","doi-asserted-by":"crossref","first-page":"713","DOI":"10.2217\/bmm.13.144","article-title":"Biomarkers of cartilage and surrounding joint tissue","volume":"8","author":"Siebuhr","year":"2014","journal-title":"Biomark Med"},{"key":"2025090312090271000_8.2.e002683.26","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1097\/RHU.0000000000000150","article-title":"Serological biomarkers of joint tissue turnover predict tocilizumab response at baseline","volume":"20","author":"Bay-Jensen","year":"2014","journal-title":"J Clin Rheumatol"},{"key":"2025090312090271000_8.2.e002683.27","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1042\/CS20060274","article-title":"Regulation and enzymatic basis of bone resorption by human osteoclasts","volume":"112","author":"Fuller","year":"2007","journal-title":"Clin Sci (Lond)"},{"key":"2025090312090271000_8.2.e002683.28","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-4-45"},{"key":"2025090312090271000_8.2.e002683.29","doi-asserted-by":"publisher","DOI":"10.1186\/ar2141"},{"key":"2025090312090271000_8.2.e002683.30","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2001.16.2.328"},{"key":"2025090312090271000_8.2.e002683.31","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.145268"},{"key":"2025090312090271000_8.2.e002683.32","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-206106"},{"key":"2025090312090271000_8.2.e002683.33","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1007\/s10067-017-3588-7","article-title":"A window of opportunity for abatacept in RA: is disease duration an independent predictor of low disease activity\/remission in clinical practice?","volume":"36","author":"Harrold","year":"2017","journal-title":"Clin Rheumatol"},{"key":"2025090312090271000_8.2.e002683.34","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-206993"},{"key":"2025090312090271000_8.2.e002683.35","doi-asserted-by":"crossref","unstructured":"Emery P , Tanaka Y , Bykerk VP . Sustained remission and outcomes with abatacept plus methotrexate following stepwise dose de-escalation in patients with early rheumatoid arthritis. Rheumatol Ther 2022;in press.doi:10.1007\/s40744-022-00519-9","DOI":"10.1007\/s40744-022-00519-9"},{"key":"2025090312090271000_8.2.e002683.36","doi-asserted-by":"publisher","DOI":"10.1002\/art.27584"},{"key":"2025090312090271000_8.2.e002683.37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0084934"},{"key":"2025090312090271000_8.2.e002683.38","doi-asserted-by":"crossref","DOI":"10.3390\/cancers12102786","article-title":"Granzyme B degraded type IV collagen products in serum identify melanoma patients responding to immune checkpoint blockade","volume":"12","author":"Jensen","year":"2020","journal-title":"Cancers"},{"key":"2025090312090271000_8.2.e002683.39","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1186\/s13075-021-02610-y","article-title":"A matrix metalloproteinase-generated neoepitope of CRP can identify knee and multi-joint inflammation in osteoarthritis","volume":"23","author":"Alexander","year":"2021","journal-title":"Arthritis Res Ther"},{"key":"2025090312090271000_8.2.e002683.40","first-page":"403","article-title":"Circulating levels of citrullinated and MMP-degraded vimentin (VICM) in liver fibrosis related pathology","volume":"4","author":"Vassiliadis","year":"2012","journal-title":"Am J Transl Res"},{"key":"2025090312090271000_8.2.e002683.41","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2007.080713"},{"key":"2025090312090271000_8.2.e002683.42","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3007764"},{"key":"2025090312090271000_8.2.e002683.43","unstructured":"Pagana KD , Pagana TJ , Pagana TN . Mosby\u2019s Diagnostic and Laboratory Test Reference. 14th Edition. Mosby, 2019."}],"container-title":["RMD Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/rmdopen-2022-002683","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T19:09:10Z","timestamp":1756926550000},"score":1,"resource":{"primary":{"URL":"https:\/\/rmdopen.bmj.com\/lookup\/doi\/10.1136\/rmdopen-2022-002683"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12]]},"references-count":43,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,12,30]]},"published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1136\/rmdopen-2022-002683"],"URL":"https:\/\/doi.org\/10.1136\/rmdopen-2022-002683","relation":{},"ISSN":["2056-5933"],"issn-type":[{"value":"2056-5933","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12]]}}}