{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T11:42:52Z","timestamp":1760182972957,"version":"build-2065373602"},"reference-count":50,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T00:00:00Z","timestamp":1564617600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T00:00:00Z","timestamp":1564617600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/100006483","name":"Abbvie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004337","name":"Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004337","id-type":"DOI","asserted-by":"publisher"}]},{"name":"BMS"},{"name":"Lilly"},{"name":"MSD"},{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","theclinics.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Rheumatic Disease Clinics of North America"],"published-print":{"date-parts":[[2019,8]]},"DOI":"10.1016\/j.rdc.2019.04.002","type":"journal-article","created":{"date-parts":[[2019,6,5]],"date-time":"2019-06-05T08:15:23Z","timestamp":1559722523000},"page":"315-324","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"title":["Does Triple Conventional Synthetic Disease-Modifying Antirheumatic Drug Therapy Improve upon Methotrexate as the Initial Treatment of Choice for a Rheumatoid Arthritis Patient?"],"prefix":"10.1016","volume":"45","author":[{"given":"Daniel","family":"Aletaha","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josef S.","family":"Smolen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"issue":"13","key":"10.1016\/j.rdc.2019.04.002_bib1","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1001\/jama.2018.13103","article-title":"Diagnosis and management of rheumatoid arthritis: a review","volume":"320","author":"Aletaha","year":"2018","journal-title":"JAMA"},{"issue":"3","key":"10.1016\/j.rdc.2019.04.002_bib2","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/nrd3669","article-title":"Inflammatory bone loss: pathogenesis and therapeutic intervention","volume":"11","author":"Redlich","year":"2012","journal-title":"Nat Rev Drug Discov"},{"issue":"10","key":"10.1016\/j.rdc.2019.04.002_bib3","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1136\/annrheumdis-2018-213250","article-title":"Non-classical monocytes as mediators of tissue destruction in arthritis","volume":"77","author":"Puchner","year":"2018","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.rdc.2019.04.002_bib4","doi-asserted-by":"crossref","first-page":"2784","DOI":"10.1002\/art.22052","article-title":"Measuring function in rheumatoid arthritis: identifying reversible and irreversible components","volume":"54","author":"Aletaha","year":"2006","journal-title":"Arthritis Rheum"},{"issue":"6","key":"10.1016\/j.rdc.2019.04.002_bib5","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1136\/ard.2009.114652","article-title":"Estimation of a numerical value for joint damage-related physical disability in rheumatoid arthritis clinical trials","volume":"69","author":"Smolen","year":"2010","journal-title":"Ann Rheum Dis"},{"issue":"3","key":"10.1016\/j.rdc.2019.04.002_bib6","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1136\/ard.2009.118430","article-title":"Impact of comorbidity on physical function in patients with rheumatoid arthritis","volume":"69","author":"Radner","year":"2010","journal-title":"Ann Rheum Dis"},{"issue":"4","key":"10.1016\/j.rdc.2019.04.002_bib7","doi-asserted-by":"crossref","first-page":"R131","DOI":"10.1186\/ar3442","article-title":"Cardiovascular events in early RA are a result of inflammatory burden and traditional risk factors: a five year prospective study","volume":"13","author":"Innala","year":"2011","journal-title":"Arthritis Res Ther"},{"key":"10.1016\/j.rdc.2019.04.002_bib8","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1161\/01.CIR.0000151875.21836.AE","article-title":"Depletion of endothelial progenitor cells in the peripheral blood of patients with rheumatoid arthritis","volume":"111","author":"Grisar","year":"2005","journal-title":"Circulation"},{"issue":"1","key":"10.1016\/j.rdc.2019.04.002_bib9","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1136\/annrheumdis-2015-207524","article-title":"Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force","volume":"75","author":"Smolen","year":"2016","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.rdc.2019.04.002_bib10","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"},{"issue":"12","key":"10.1016\/j.rdc.2019.04.002_bib11","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1136\/ard.2007.072157","article-title":"EULAR evidence-based recommendations on the management of systemic glucocorticoid therapy in rheumatic diseases","volume":"66","author":"Hoes","year":"2007","journal-title":"Ann Rheum Dis"},{"issue":"9","key":"10.1016\/j.rdc.2019.04.002_bib12","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1002\/1529-0131(199809)41:9<1552::AID-ART5>3.0.CO;2-W","article-title":"Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis","volume":"41","author":"Maini","year":"1998","journal-title":"Arthritis Rheum"},{"issue":"11","key":"10.1016\/j.rdc.2019.04.002_bib13","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1136\/annrheumdis-2015-208426","article-title":"Comparison of adding tocilizumab to methotrexate with switching to tocilizumab in patients with rheumatoid arthritis with inadequate response to methotrexate: 52-week results from a prospective, randomised, controlled study (SURPRISE study)","volume":"75","author":"Kaneko","year":"2016","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.rdc.2019.04.002_bib14","doi-asserted-by":"crossref","first-page":"2572","DOI":"10.1056\/NEJMoa032534","article-title":"Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis","volume":"350","author":"Edwards","year":"2004","journal-title":"N\u00a0Engl J Med"},{"issue":"3","key":"10.1016\/j.rdc.2019.04.002_bib15","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1002\/art.39953","article-title":"Baricitinib, methotrexate, or combination in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment","volume":"69","author":"Fleischmann","year":"2017","journal-title":"Arthritis Rheumatol"},{"key":"10.1016\/j.rdc.2019.04.002_bib16","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/S0140-6736(17)31618-5","article-title":"Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b\/4, double-blind, head-to-head, randomised controlled trial","volume":"390","author":"Fleischmann","year":"2017","journal-title":"Lancet"},{"key":"10.1016\/j.rdc.2019.04.002_bib17","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1056\/NEJM199605163342002","article-title":"Treatment of rheumatoid arthritis with methotrexate alone, sulfasalazine and hydroxychloroquine, or a combination of all three medications","volume":"334","author":"O'Dell","year":"1996","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.rdc.2019.04.002_bib18","doi-asserted-by":"crossref","first-page":"3360","DOI":"10.1002\/art.21298","article-title":"Low-dose prednisolone in addition to the initial disease-modifying antirheumatic drug in patients with early active rheumatoid arthritis reduces joint destruction and increases the remission rate: a two-year randomized trial","volume":"52","author":"Svensson","year":"2005","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.rdc.2019.04.002_bib19","doi-asserted-by":"crossref","first-page":"3371","DOI":"10.1002\/art.21421","article-title":"Very low-dose prednisolone in early rheumatoid arthritis retards radiographic progression over two years: a multicenter, double-blind, placebo-controlled trial","volume":"52","author":"Wassenberg","year":"2005","journal-title":"Arthritis Rheum"},{"issue":"1","key":"10.1016\/j.rdc.2019.04.002_bib20","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1136\/annrheumdis-2013-203440","article-title":"Remission induction comparing infliximab and high-dose intravenous steroid, followed by treat-to-target: a double-blind, randomised, controlled trial in new-onset, treatment-naive, rheumatoid arthritis (the IDEA study)","volume":"73","author":"Nam","year":"2014","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.rdc.2019.04.002_bib21","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1136\/annrheumdis-2015-209057","article-title":"Certolizumab pegol in combination with dose-optimised methotrexate in DMARD-naive patients with early, active rheumatoid arthritis with poor prognostic factors: 1-year results from C-EARLY, a randomised, double-blind, placebo-controlled phase III study","volume":"76","author":"Emery","year":"2017","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.rdc.2019.04.002_bib22","doi-asserted-by":"crossref","first-page":"3432","DOI":"10.1002\/art.20568","article-title":"Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial","volume":"50","author":"St Clair","year":"2004","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.rdc.2019.04.002_bib23","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.1002\/art.21293","article-title":"Superior efficacy of combination therapy for rheumatoid arthritis. fact or fiction?","volume":"52","author":"Smolen","year":"2005","journal-title":"Arthritis Rheum"},{"issue":"9164","key":"10.1016\/j.rdc.2019.04.002_bib24","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1016\/S0140-6736(98)08513-4","article-title":"Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial. FIN-RACo trial group","volume":"353","author":"Mottonen","year":"1999","journal-title":"Lancet"},{"issue":"1308","key":"10.1016\/j.rdc.2019.04.002_bib25","first-page":"1315","article-title":"Preliminary criteria for clinical remission in rheumatoid arthritis","volume":"24","author":"Pinals","year":"1981","journal-title":"Arthritis Rheum"},{"issue":"7","key":"10.1016\/j.rdc.2019.04.002_bib26","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1136\/annrheumdis-2013-204788","article-title":"Randomised comparison of initial triple DMARD therapy with methotrexate monotherapy in combination with low-dose glucocorticoid bridging therapy; 1-year data of the tREACH trial","volume":"73","author":"de Jong","year":"2014","journal-title":"Ann Rheum Dis"},{"issue":"1","key":"10.1016\/j.rdc.2019.04.002_bib27","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1136\/annrheumdis-2014-205489","article-title":"Methotrexate in combination with other DMARDs is not superior to methotrexate alone for remission induction with\u00a0moderate-to-high-dose glucocorticoid bridging in early rheumatoid arthritis after 16\u00a0weeks of treatment: the CareRA trial","volume":"74","author":"Verschueren","year":"2015","journal-title":"Ann Rheum Dis"},{"issue":"6","key":"10.1016\/j.rdc.2019.04.002_bib28","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1136\/annrheumdis-2016-210711","article-title":"Efficacy of glucocorticoids, conventional and targeted synthetic disease-modifying antirheumatic drugs: a systematic literature review informing the 2016 update of the EULAR recommendations for the management of rheumatoid arthritis","volume":"76","author":"Chatzidionysiou","year":"2017","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.rdc.2019.04.002_bib29","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1136\/annrheumdis-2016-210715","article-title":"EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update","volume":"76","author":"Smolen","year":"2017","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.rdc.2019.04.002_bib30","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1136\/ard.2008.101121","article-title":"Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors","volume":"68","author":"Westhovens","year":"2009","journal-title":"Ann Rheum Dis"},{"issue":"1","key":"10.1016\/j.rdc.2019.04.002_bib31","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1136\/ard.2010.137703","article-title":"Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate in early active rheumatoid arthritis: the IMAGE trial","volume":"70","author":"Tak","year":"2011","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.rdc.2019.04.002_bib32","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1136\/annrheumdis-2015-207628","article-title":"Tocilizumab in early progressive rheumatoid arthritis: FUNCTION, a randomised controlled trial","volume":"75","author":"Burmester","year":"2015","journal-title":"Ann Rheum Dis"},{"issue":"Suppl 10","key":"10.1016\/j.rdc.2019.04.002_bib33","article-title":"Baricitinib, methotrexate, or baricitinib plus methotrexate in patients with early rheumatoid arthritis who had received limited or no treatment with disease-modifying anti-rheumatic drugs (DMARDs): phase 3 trial results","volume":"67","author":"Fleischmann","year":"2015","journal-title":"Arthritis Rheum"},{"issue":"25","key":"10.1016\/j.rdc.2019.04.002_bib34","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1056\/NEJMoa1310476","article-title":"Tofacitinib versus methotrexate in rheumatoid arthritis","volume":"370","author":"Lee","year":"2014","journal-title":"N\u00a0Engl J Med"},{"issue":"7","key":"10.1016\/j.rdc.2019.04.002_bib35","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1136\/annrheumdis-2013-203243","article-title":"A\u00a0two-step treatment strategy trial in patients with early arthritis aimed at achieving remission: the IMPROVED study","volume":"73","author":"Heimans","year":"2014","journal-title":"Ann Rheum Dis"},{"issue":"9","key":"10.1016\/j.rdc.2019.04.002_bib36","doi-asserted-by":"crossref","first-page":"2824","DOI":"10.1002\/art.34498","article-title":"A\u00a0randomized comparative effectiveness study of oral triple therapy versus etanercept plus methotrexate in early aggressive rheumatoid arthritis: the treatment of early aggressive rheumatoid arthritis trial","volume":"64","author":"Moreland","year":"2012","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.rdc.2019.04.002_bib37","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1056\/NEJMoa1303006","article-title":"Therapies for active rheumatoid arthritis after methotrexate failure","volume":"369","author":"O'Dell","year":"2013","journal-title":"N\u00a0Engl J Med"},{"issue":"6","key":"10.1016\/j.rdc.2019.04.002_bib38","doi-asserted-by":"crossref","first-page":"263","DOI":"10.5414\/CP203202","article-title":"Comparative efficacy and safety of TNF-inhibitor plus methotrexate versus oral triple therapy in patients with active rheumatoid arthritis inadequately responding to methotrexate: a meta-analysis of randomized controlled trials","volume":"56","author":"Bae","year":"2018","journal-title":"Int J Clin Pharmacol Ther"},{"issue":"1","key":"10.1016\/j.rdc.2019.04.002_bib39","doi-asserted-by":"crossref","first-page":"e000371","DOI":"10.1136\/rmdopen-2016-000371","article-title":"Systematic review and network meta-analysis of the efficacy and safety of tumour necrosis factor inhibitor-methotrexate combination therapy versus triple therapy in rheumatoid arthritis","volume":"3","author":"Fleischmann","year":"2017","journal-title":"RMD Open"},{"key":"10.1016\/j.rdc.2019.04.002_bib40","article-title":"Low persistence rates in rheumatoid arthritis patients treated with triple therapy are attributed to adverse drug events associated with sulfasalazine","author":"Erhardt","year":"2018","journal-title":"Arthritis Care Res (Hoboken)"},{"issue":"3","key":"10.1016\/j.rdc.2019.04.002_bib41","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1136\/annrheumdis-2016-209212","volume":"76","author":"Verschueren","year":"2017","journal-title":"Ann Rheum Dis"},{"issue":"2","key":"10.1016\/j.rdc.2019.04.002_bib42","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1136\/annrheumdis-2017-211937","article-title":"Consensus-based recommendations for the use of biosimilars to treat rheumatological diseases","volume":"77","author":"Kay","year":"2018","journal-title":"Ann Rheum Dis"},{"issue":"2","key":"10.1016\/j.rdc.2019.04.002_bib43","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1136\/ard.2007.071415","article-title":"Treatment-related improvement in physical function varies with duration of rheumatoid arthritis: a pooled analysis of clinical trial results","volume":"67","author":"Aletaha","year":"2008","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.rdc.2019.04.002_bib44","doi-asserted-by":"crossref","DOI":"10.1016\/j.semarthrit.2019.02.004","article-title":"Risk profiling for a refractory course of rheumatoid arthritis","author":"Becede","year":"2019","journal-title":"Semin Arthritis Rheum"},{"issue":"5","key":"10.1016\/j.rdc.2019.04.002_bib45","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1093\/rheumatology\/keq406","article-title":"Outcome in rheumatoid arthritis patients with continued conventional therapy for moderate disease activity\u2014the early RA network (ERAN)","volume":"50","author":"Kiely","year":"2011","journal-title":"Rheumatology (Oxford)"},{"issue":"Suppl 3","key":"10.1016\/j.rdc.2019.04.002_bib46","doi-asserted-by":"crossref","first-page":"iii56","DOI":"10.1136\/ard.2007.078360","article-title":"Tight control in the treatment of rheumatoid arthritis: efficacy and feasibility","volume":"66","author":"Bakker","year":"2007","journal-title":"Ann Rheum Dis"},{"issue":"12","key":"10.1016\/j.rdc.2019.04.002_bib47","doi-asserted-by":"crossref","first-page":"3702","DOI":"10.1002\/art.30634","article-title":"Joint damage in rheumatoid arthritis progresses in remission according to the Disease Activity Score in 28 joints and is driven by residual swollen joints","volume":"63","author":"Aletaha","year":"2011","journal-title":"Arthritis Rheum"},{"year":"2013","series-title":"Guidance for industry\u2014rheumatoid arthritis: developing drug products for treatment. Draft gudance","author":"Food and Drug Administration","key":"10.1016\/j.rdc.2019.04.002_bib48"},{"issue":"1","key":"10.1016\/j.rdc.2019.04.002_bib49","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/art.27740","article-title":"Interleukin-6 receptor inhibition with tocilizumab and attainment of disease remission in rheumatoid arthritis: the role of acute-phase reactants","volume":"63","author":"Smolen","year":"2011","journal-title":"Arthritis Rheum"},{"issue":"4","key":"10.1016\/j.rdc.2019.04.002_bib50","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1002\/art.39996","article-title":"Brief report: remission rates with tofacitinib treatment in rheumatoid arthritis: a comparison of various remission criteria","volume":"69","author":"Smolen","year":"2017","journal-title":"Arthritis Rheumatol"}],"container-title":["Rheumatic Disease Clinics of North America"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0889857X19300298?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0889857X19300298?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T11:17:19Z","timestamp":1760181439000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0889857X19300298"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8]]},"references-count":50,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,8]]}},"alternative-id":["S0889857X19300298"],"URL":"https:\/\/doi.org\/10.1016\/j.rdc.2019.04.002","relation":{},"ISSN":["0889-857X"],"issn-type":[{"type":"print","value":"0889-857X"}],"subject":[],"published":{"date-parts":[[2019,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Does Triple Conventional Synthetic Disease-Modifying Antirheumatic Drug Therapy Improve upon Methotrexate as the Initial Treatment of Choice for a Rheumatoid Arthritis Patient?","name":"articletitle","label":"Article Title"},{"value":"Rheumatic Disease Clinics of North America","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.rdc.2019.04.002","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}