{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:57:40Z","timestamp":1772161060352,"version":"3.50.1"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2015,5,31]],"date-time":"2015-05-31T00:00:00Z","timestamp":1433030400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2015,5,31]],"date-time":"2015-05-31T00:00:00Z","timestamp":1433030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Rheumatol Int"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>\nThe multi-biomarker disease activity (MBDA) score measures 12 proteins involved in the pathophysiology of rheumatoid arthritis (RA) to assess disease activity (DA). Previous studies demonstrated correlations between MBDA and clinical DA scores with some RA therapies. In this analysis, the relationship between DA and MBDA scores and changes in MBDA component biomarkers were evaluated in tocilizumab (TCZ)-treated patients. Patients from the ACT-RAY study were included in this analysis if they had DA measures and serum collected at pre-specified time points with sufficient serum for MBDA testing at \u22651 visit. Descriptive statistics, associations between outcomes, and percentage agreement between DA categories were calculated. Seventy-eight patients were included and were similar to the ACT-RAY population. Correlations between MBDA score and DAS28-CRP were <jats:italic>\u03c1<\/jats:italic>\u00a0=\u00a00.50 at baseline and <jats:italic>\u03c1<\/jats:italic>\u00a0=\u00a00.26 at week 24. Agreement between low\/moderate\/high categories of MBDA score and DAS28-CRP was observed for 77.1\u00a0% of patients at baseline and 23.7\u00a0% at week 24. Mean changes from baseline to weeks 4, 12, and 24 were proportionately smaller for MBDA score than DAS28-CRP. Unlike some other MBDA biomarkers, interleukin-6 (IL-6) concentrations increased in most patients during TCZ treatment. Correlations and agreement between MBDA and DAS28-CRP or CDAI scores were lower at week 24 versus baseline. The proportionately smaller magnitude of response observed for MBDA score versus DAS28-CRP may be due to the influence of the increase in IL-6 concentrations on MBDA score. Thus, MBDA scores obtained during TCZ treatment should be interpreted cautiously and in the context of available clinical information.<\/jats:p>","DOI":"10.1007\/s00296-015-3285-2","type":"journal-article","created":{"date-parts":[[2015,5,30]],"date-time":"2015-05-30T06:23:55Z","timestamp":1432967035000},"page":"295-300","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Interpreting the multi-biomarker disease activity score in the context of tocilizumab treatment for patients with rheumatoid arthritis"],"prefix":"10.1007","volume":"36","author":[{"given":"William G.","family":"Reiss","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenny N.","family":"Devenport","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason M.","family":"Low","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric H.","family":"Sasso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,5,31]]},"reference":[{"key":"3285_CR1","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1016\/S0140-6736(08)60453-5","volume":"371","author":"JS Smolen","year":"2008","unstructured":"Smolen JS, Beaulieu A, Rubbert-Roth A et al (2008) Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet 371:987\u2013997","journal-title":"Lancet"},{"key":"3285_CR2","doi-asserted-by":"publisher","first-page":"2968","DOI":"10.1002\/art.23940","volume":"58","author":"MC Genovese","year":"2008","unstructured":"Genovese MC, McKay JD, Nasonov EL et al (2008) Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: the tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study. Arthritis Rheum 58:2968\u20132980","journal-title":"Arthritis Rheum"},{"key":"3285_CR3","doi-asserted-by":"publisher","first-page":"1516","DOI":"10.1136\/ard.2008.092932","volume":"67","author":"P Emery","year":"2008","unstructured":"Emery P, Keystone E, Tony HP et al (2008) IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis 67:1516\u20131523","journal-title":"Ann Rheum Dis"},{"key":"3285_CR4","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1002\/art.30158","volume":"63","author":"JM Kremer","year":"2011","unstructured":"Kremer JM, Blanco R, Brzosko M et al (2011) Tocilizumab inhibits structural joint damage in rheumatoid arthritis patients with inadequate responses to methotrexate: results from the double-blind treatment phase of a randomized placebo-controlled trial of tocilizumab safety and prevention of structural joint damage at one year. Arthritis Rheum 63:609\u2013621","journal-title":"Arthritis Rheum"},{"key":"3285_CR5","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1136\/ard.2008.105197","volume":"69","author":"G Jones","year":"2010","unstructured":"Jones G, Sebba A, Gu J et al (2010) Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis 69:88\u201396","journal-title":"Ann Rheum Dis"},{"key":"3285_CR6","doi-asserted-by":"publisher","first-page":"3959","DOI":"10.1182\/blood-2008-05-155846","volume":"112","author":"N Nishimoto","year":"2008","unstructured":"Nishimoto N, Terao K, Mima T et al (2008) Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease. Blood 112:3959\u20133964","journal-title":"Blood"},{"key":"3285_CR7","doi-asserted-by":"publisher","first-page":"1595","DOI":"10.1016\/j.intimp.2008.07.002","volume":"8","author":"Y Uchiyama","year":"2008","unstructured":"Uchiyama Y, Yoshida H, Koike N et al (2008) Anti-IL-6 receptor antibody increases blood IL-6 level via the blockade of IL-6 clearance, but not via the induction of IL-6 production. Int Immunopharmacol 8:1595\u20131601","journal-title":"Int Immunopharmacol"},{"key":"3285_CR8","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.2169\/internalmedicine.50.4771","volume":"50","author":"Y Yoshida","year":"2011","unstructured":"Yoshida Y, Sakamoto M, Yokota K et al (2011) Tocilizumab improved both clinical and laboratory manifestations except for interleukin-18 in a case of multiple drug-resistant adult-onset Still\u2019s disease. Intern Med 50:1757\u20131760","journal-title":"Intern Med"},{"key":"3285_CR9","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1056\/NEJM199902113400607","volume":"340","author":"C Gabay","year":"1999","unstructured":"Gabay C, Kushner I (1999) Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 340:448\u2013454","journal-title":"N Engl J Med"},{"key":"3285_CR10","first-page":"1426","volume":"30","author":"N Nishimoto","year":"2003","unstructured":"Nishimoto N, Yoshizaki K, Maeda K et al (2003) Toxicity, pharmacokinetics, and dose-finding study of repetitive treatment with the humanized anti-interleukin 6 receptor antibody MRA in rheumatoid arthritis. Phase I\/II clinical study. J Rheumatol 30:1426\u20131435","journal-title":"J Rheumatol"},{"key":"3285_CR11","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1136\/ard.2009.126532","volume":"69","author":"JS Smolen","year":"2010","unstructured":"Smolen JS, Landewe R, Breedveld FC et al (2010) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis 69:964\u2013975","journal-title":"Ann Rheum Dis"},{"key":"3285_CR12","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1002\/acr.21641","volume":"64","author":"JA Singh","year":"2012","unstructured":"Singh JA, Furst DE, Bharat A et al (2012) 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken) 64:625\u2013639","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"3285_CR13","first-page":"S109","volume":"23","author":"T Pincus","year":"2005","unstructured":"Pincus T (2005) The American College of Rheumatology (ACR) core data set and derivative \u201cpatient only\u201d indices to assess rheumatoid arthritis. Clin Exp Rheumatol 23:S109\u2013S113","journal-title":"Clin Exp Rheumatol"},{"key":"3285_CR14","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1177\/000456329303000404","volume":"30","author":"GH Clark","year":"1993","unstructured":"Clark GH, Fraser CG (1993) Biological variation of acute phase proteins. Ann Clin Biochem 30:373\u2013376","journal-title":"Ann Clin Biochem"},{"key":"3285_CR15","doi-asserted-by":"publisher","first-page":"e60635","DOI":"10.1371\/journal.pone.0060635","volume":"8","author":"M Centola","year":"2013","unstructured":"Centola M, Cavet G, Shen Y et al (2013) Development of a multi-biomarker disease activity test for rheumatoid arthritis. PLoS One 8:e60635","journal-title":"PLoS One"},{"key":"3285_CR16","doi-asserted-by":"publisher","first-page":"1202","DOI":"10.1093\/rheumatology\/kes362","volume":"52","author":"S Hirata","year":"2013","unstructured":"Hirata S, Dirven L, Shen Y et al (2013) A multi-biomarker score measures rheumatoid arthritis disease activity in the BeSt study. Rheumatology (Oxford) 52:1202\u20131207","journal-title":"Rheumatology (Oxford)"},{"key":"3285_CR17","doi-asserted-by":"publisher","first-page":"1692","DOI":"10.1136\/annrheumdis-2011-200963","volume":"71","author":"MF Bakker","year":"2012","unstructured":"Bakker MF, Cavet G, Jacobs JW et al (2012) Performance of a multi-biomarker score measuring rheumatoid arthritis disease activity in the CAMERA tight control study. Ann Rheum Dis 71:1692\u20131697","journal-title":"Ann Rheum Dis"},{"key":"3285_CR18","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1136\/annrheumdis-2011-201282","volume":"72","author":"M Dougados","year":"2013","unstructured":"Dougados M, Kissel K, Sheeran T et al (2013) Adding tocilizumab or switching to tocilizumab monotherapy in methotrexate inadequate responders: 24-week symptomatic and structural results of a 2-year randomised controlled strategy trial in rheumatoid arthritis (ACT-RAY). Ann Rheum Dis 72:43\u201350","journal-title":"Ann Rheum Dis"},{"key":"3285_CR19","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/j.jpba.2012.06.003","volume":"70","author":"PS Eastman","year":"2012","unstructured":"Eastman PS, Manning WC, Qureshi F et al (2012) Characterization of a multiplex, 12-biomarker test for rheumatoid arthritis. J Pharm Biomed Anal 70:415\u2013424","journal-title":"J Pharm Biomed Anal"},{"key":"3285_CR20","doi-asserted-by":"publisher","first-page":"1794","DOI":"10.1002\/acr.21767","volume":"64","author":"JR Curtis","year":"2012","unstructured":"Curtis JR, van der Helm-van Mil AH, Knevel R et al (2012) Validation of a novel multibiomarker test to assess rheumatoid arthritis disease activity. Arthritis Care Res (Hoboken) 64:1794\u20131803","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"3285_CR21","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1002\/art.1780380107","volume":"38","author":"ML Prevoo","year":"1995","unstructured":"Prevoo ML, van \u2018t Hof MA, Kuper HH et al (1995) Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 38:44\u201348","journal-title":"Arthritis Rheum"},{"key":"3285_CR22","doi-asserted-by":"publisher","first-page":"R796","DOI":"10.1186\/ar1740","volume":"7","author":"D Aletaha","year":"2005","unstructured":"Aletaha D, Nell VP, Stamm T et al (2005) Acute phase reactants add little to composite disease activity indices for rheumatoid arthritis: validation of a clinical activity score. Arthritis Res Ther 7:R796\u2013R806","journal-title":"Arthritis Res Ther"},{"key":"3285_CR23","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1136\/ard.2006.054205","volume":"66","author":"E Inoue","year":"2007","unstructured":"Inoue E, Yamanaka H, Hara M et al (2007) Comparison of Disease Activity Score (DAS)28- erythrocyte sedimentation rate and DAS28-\u00a0C-reactive protein threshold values. Ann Rheum Dis 66:407\u2013409","journal-title":"Ann Rheum Dis"},{"key":"3285_CR24","doi-asserted-by":"publisher","first-page":"2625","DOI":"10.1002\/art.21235","volume":"52","author":"D Aletaha","year":"2005","unstructured":"Aletaha D, Ward MM, Machold KP et al (2005) Remission and active disease in rheumatoid arthritis: defining criteria for disease activity states. Arthritis Rheum 52:2625\u20132636","journal-title":"Arthritis Rheum"},{"issue":"suppl3","key":"3285_CR25","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1136\/annrheumdis-2013-eular.1193","volume":"72","author":"K Hanami","year":"2013","unstructured":"Hanami K, Hirata S, Tasaka H et al (2013) Behavior of the multi-biomarker disease activity (Vectra DA algorithm) score and components in patients with rheumatoid arthritis treated with tocilizumab. Ann Rheum Dis 72(suppl3):391","journal-title":"Ann Rheum Dis"},{"key":"3285_CR26","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.3899\/jrheum.121389","volume":"40","author":"K Shimamoto","year":"2013","unstructured":"Shimamoto K, Ito T, Ozaki Y et al (2013) Serum interleukin 6 before and after therapy with tocilizumab is a principal biomarker in patients with rheumatoid arthritis. J Rheumatol 40:1074\u20131081","journal-title":"J Rheumatol"}],"container-title":["Rheumatology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00296-015-3285-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00296-015-3285-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00296-015-3285-2","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00296-015-3285-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T15:12:31Z","timestamp":1630595551000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00296-015-3285-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,5,31]]},"references-count":26,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2016,2]]}},"alternative-id":["3285"],"URL":"https:\/\/doi.org\/10.1007\/s00296-015-3285-2","relation":{},"ISSN":["0172-8172","1437-160X"],"issn-type":[{"value":"0172-8172","type":"print"},{"value":"1437-160X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,5,31]]},"assertion":[{"value":"2 February 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 May 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 May 2015","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}