{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T01:27:25Z","timestamp":1768267645179,"version":"3.49.0"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,12,4]],"date-time":"2019-12-04T00:00:00Z","timestamp":1575417600000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007013","name":"F. Hoffmann-La Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007013","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004328","name":"Genentech","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004328","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Adv Rheumatol"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Tocilizumab (TCZ), a humanized monoclonal antibody against the interleukin-6 receptor, has been proven to be a safe and effective treatment for rheumatoid arthritis (RA). Because RA is a heterogenous disease and patient response to treatments can vary, identifying characteristics that predict which patients are more likely to respond to TCZ is important for optimal patient care. Serum levels of C-X-C motif chemokine ligand 13 (CXCL13) and soluble intercellular adhesion molecule-1 (sICAM-1) have been associated with response to TCZ in patients with RA.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Objectives<\/jats:title>\n<jats:p>To evaluate the association of CXCL13 and sICAM-1 with disease activity and response to TCZ in patients with early RA and those with inadequate response to disease-modifying antirheumatic drugs (DMARD-IR).<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Baseline and week 24 serum CXCL13 and sICAM-1 levels were measured using available patient samples from the FUNCTION (early RA) and LITHE (DMARD-IR) trials. Correlations between CXCL13 and sICAM-1 levels and Disease Activity Score in 28 joints calculated with erythrocyte sedimentation rate (DAS28-ESR) at baseline and between change in CXCL13 and sICAM-1 and change in DAS28-ESR at week 24 were estimated. CXCL13 and sICAM-1 changes from baseline to week 24 were compared between treatment arms. The effects of TCZ treatment and baseline DAS28-ESR, CXCL13 and sICAM-1 levels on DAS28-ESR remission and 50% improvement per the American College of Rheumatology (ACR50) response at week 24 were determined.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Overall, 458 patients from FUNCTION and 287 patients from LITHE were included. Correlation of baseline serum CXCL13 and sICAM-1 levels with DAS28-ESR was weak to moderate. CXCL13 and sICAM-1 levels decreased significantly at week 24 in TCZ-treated patients in both the early-RA and DMARD-IR populations. CXCL13 and sICAM-1 changes correlated moderately to weakly with DAS28-ESR changes at week 24 in both populations. The treatment regimen, but not baseline CXCL13 and sICAM-1 levels, had a significant effect on the likelihood of DAS28-ESR remission and ACR50 response.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Although CXCL13 and sICAM-1 are modestly associated with RA disease activity, they do not predict response to TCZ in all RA populations.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s42358-019-0097-1","type":"journal-article","created":{"date-parts":[[2019,12,4]],"date-time":"2019-12-04T16:03:16Z","timestamp":1575475396000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Levels of CXCL13 and sICAM-1 correlate with disease activity score in patients with rheumatoid arthritis treated with tocilizumab"],"prefix":"10.1186","volume":"59","author":[{"given":"Katie","family":"Tuckwell","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cem","family":"Gabay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thierry","family":"Sornasse","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruediger Paul","family":"Laubender","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianmei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Townsend","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,12,4]]},"reference":[{"key":"97_CR1","doi-asserted-by":"publisher","first-page":"79","DOI":"10.3109\/00365513.2010.493406","volume":"242","author":"TM Lindstrom","year":"2010","unstructured":"Lindstrom TM, Robinson WH. Biomarkers for rheumatoid arthritis: making it personal. Scand J Clin Lab Invest Suppl. 2010;242:79\u201384.","journal-title":"Scand J Clin Lab Invest Suppl"},{"issue":"1","key":"97_CR2","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1186\/ar2557","volume":"11","author":"LG van Baarsen","year":"2009","unstructured":"van Baarsen LG, Bos CL, van der Pouw Kraan TC, Verweij CL. Transcription profiling of rheumatic diseases. Arthritis Res Ther. 2009;11(1):207.","journal-title":"Arthritis Res Ther."},{"issue":"3","key":"97_CR3","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1038\/sj.gene.6363975","volume":"4","author":"TC van der Pouw Kraan","year":"2003","unstructured":"van der Pouw Kraan TC, van Gaalen FA, Huizinga TW, Pieterman E, Breedveld FC, Verweij CL. Discovery of distinctive gene expression profiles in rheumatoid synovium using cDNA microarray technology: evidence for the existence of multiple pathways of tissue destruction and repair. Genes Immun. 2003;4(3):187\u201396.","journal-title":"Genes Immun"},{"issue":"2","key":"97_CR4","doi-asserted-by":"publisher","first-page":"R90","DOI":"10.1186\/ar4555","volume":"16","author":"G Dennis Jr","year":"2014","unstructured":"Dennis G Jr, Holweg CT, Kummerfeld SK, Choy DF, Setiadi AF, Hackney JA, et al. Synovial phenotypes in rheumatoid arthritis correlate with response to biologic therapeutics. Arthritis Res Ther. 2014;16(2):R90.","journal-title":"Arthritis Res Ther."},{"issue":"10","key":"97_CR5","doi-asserted-by":"publisher","first-page":"2601","DOI":"10.1002\/art.39235","volume":"67","author":"F Humby","year":"2015","unstructured":"Humby F, Kelly S, Hands R, Rocher V, DiCicco M, Ng N, et al. Use of ultrasound-guided small joint biopsy to evaluate the histopathologic response to rheumatoid arthritis therapy: recommendations for application to clinical trials. 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CXCL13 predicts disease activity in early rheumatoid arthritis and could be an indicator of the therapeutic \u2018window of opportunity\u2019. Arthritis Res Ther. 2014;16(5):434\u2013014 -0434-z.","journal-title":"Arthritis Res Ther"},{"issue":"1","key":"97_CR12","doi-asserted-by":"publisher","first-page":"e000607","DOI":"10.1136\/rmdopen-2017-000607","volume":"4","author":"C Gabay","year":"2018","unstructured":"Gabay C, Msihid J, Zilberstein M, Paccard C, Lin Y, Graham NMH, et al. Identification of sarilumab pharmacodynamic and predictive markers in patients with inadequate response to TNF inhibition: a biomarker substudy of the phase 3 TARGET study. RMD Open. 2018;4(1):e000607\u20132017 eCollection 2018.","journal-title":"RMD Open"}],"container-title":["Advances in Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s42358-019-0097-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s42358-019-0097-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s42358-019-0097-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T02:19:51Z","timestamp":1606961991000},"score":1,"resource":{"primary":{"URL":"https:\/\/advancesinrheumatology.biomedcentral.com\/articles\/10.1186\/s42358-019-0097-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12]]},"references-count":12,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["97"],"URL":"https:\/\/doi.org\/10.1186\/s42358-019-0097-1","relation":{},"ISSN":["2523-3106"],"issn-type":[{"value":"2523-3106","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12]]},"assertion":[{"value":"21 May 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 November 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 December 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The FUNCTION and LITHE study protocols were approved by an ethics committee or institutional review board at each participating center before the start of the study. All patients provided written informed consent in accordance with the Declaration of Helsinki.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"K Tuckwell and M Townsend are employees of Genentech, Inc. C Gabay has received research funding from Roche, Pfizer, and AB2 Bio and fees as consultant and speaker from Roche, Pfizer, AbbVie, Novartis, and Sanofi. T Sornasse was an employee of Genentech, Inc., at the time of the study. R Laubender is an employee of Roche Diagnostics GmbH. J Wang is an employee of Roche Products Ltd.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"54"}}