{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:47:43Z","timestamp":1791478063260,"version":"4.3.4"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,4,18]],"date-time":"2019-04-18T00:00:00Z","timestamp":1555545600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"published-print":{"date-parts":[[2019,12]]},"DOI":"10.1186\/s13075-019-1879-x","type":"journal-article","created":{"date-parts":[[2019,4,18]],"date-time":"2019-04-18T09:07:39Z","timestamp":1555578459000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":81,"title":["Efficacy and safety of namilumab, a human monoclonal antibody against granulocyte-macrophage colony-stimulating factor (GM-CSF) ligand in patients with rheumatoid arthritis (RA) with either an inadequate response to background methotrexate therapy or an inadequate response or intolerance to an anti-TNF (tumour necrosis factor) biologic therapy: a randomized, controlled trial"],"prefix":"10.1186","volume":"21","author":[{"name":"for the NEXUS Study Group","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7766-6167","authenticated-orcid":false,"given":"Peter C.","family":"Taylor","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier","family":"Saurigny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiri","family":"Vencovsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Takeuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galina","family":"Matsievskaia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Hunt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Souberbielle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,4,18]]},"reference":[{"key":"1879_CR1","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1016\/S0140-6736(10)60826-4","volume":"376","author":"DL Scott","year":"2010","unstructured":"Scott DL, Wolfe F, Huizinga TW. Rheumatoid arthritis. Lancet. 2010;376:1094\u2013108.","journal-title":"Lancet"},{"key":"1879_CR2","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1136\/ard.2007.072447","volume":"66","author":"W Kievit","year":"2007","unstructured":"Kievit W, Fransen J, Oerlemans AJ, Kuper HH, van der Laar MA, de Rooij DJ, et al. The efficacy of anti-TNF in rheumatoid arthritis, a comparison between randomised controlled trials and clinical practice. Ann Rheum Dis. 2007;66:1473\u20138.","journal-title":"Ann Rheum Dis"},{"key":"1879_CR3","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1002\/art.27227","volume":"62","author":"ML Hetland","year":"2010","unstructured":"Hetland ML, Christensen IJ, Tarp U, Dreyer L, Hansen A, Hansen IT, et al. Direct comparison of treatment responses, remission rates, and drug adherence in patients with rheumatoid arthritis treated with adalimumab, etanercept, or infliximab: results from eight years of surveillance of clinical practice in the nationwide Danish DANBIO registry. Arthritis Rheum. 2010;62:22\u201332.","journal-title":"Arthritis Rheum"},{"key":"1879_CR4","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1615\/CritRevImmunol.v25.i5.50","volume":"25","author":"AJ Fleetwood","year":"2005","unstructured":"Fleetwood AJ, Cook AD, Hamilton JA. Functions of granulocyte-macrophage colony-stimulating factor. Crit Rev Immunol. 2005;25:405\u201328.","journal-title":"Crit Rev Immunol"},{"key":"1879_CR5","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1038\/nri2356","volume":"8","author":"JA Hamilton","year":"2008","unstructured":"Hamilton JA. Colony-stimulating factors in inflammation and autoimmunity. Nat Rev Immunol. 2008;8:533\u201344.","journal-title":"Nat Rev Immunol"},{"issue":"Suppl 1","key":"1879_CR6","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1002\/stem.5530080705","volume":"8","author":"JD Griffin","year":"1990","unstructured":"Griffin JD, Cannistra SA, Sullivan R, Demetri GD, Ernst TJ, Kanakura Y. The biology of GM-CSF: regulation of production and interaction with its receptor. Int J Cell Cloning. 1990;8(Suppl 1):35\u201344 (discussion 44-5).","journal-title":"Int J Cell Cloning"},{"key":"1879_CR7","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1182\/blood.V77.6.1131.1131","volume":"77","author":"JC Gasson","year":"1991","unstructured":"Gasson JC. Molecular physiology of granulocyte-macrophage colony-stimulating factor. Blood. 1991;77:1131\u201345.","journal-title":"Blood"},{"key":"1879_CR8","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1586\/1744666X.2015.1024110","volume":"11","author":"JA Hamilton","year":"2015","unstructured":"Hamilton JA. GM-CSF as a target in inflammatory\/autoimmune disease: current evidence and future therapeutic potential. Expert Rev Clin Immunol. 2015;11:457\u201365.","journal-title":"Expert Rev Clin Immunol"},{"key":"1879_CR9","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1080\/08977190412331279881","volume":"22","author":"JA Hamilton","year":"2004","unstructured":"Hamilton JA, Anderson GP. GM-CSF biology. Growth Factors. 2004;22:225\u201331.","journal-title":"Growth Factors"},{"key":"1879_CR10","doi-asserted-by":"publisher","first-page":"203","DOI":"10.3109\/03009748809102970","volume":"17","author":"NJ Zvaifler","year":"1988","unstructured":"Zvaifler NJ, Firestein GS. Cytokines in chronic inflammatory synovitis. Scand J Rheumatol. 1988;17:203\u201310.","journal-title":"Scand J Rheumatol"},{"key":"1879_CR11","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1172\/JCI113971","volume":"83","author":"WD Xu","year":"1989","unstructured":"Xu WD, Firestein GS, Taetle R, Kaushansky K, Zvaifler NJ. Cytokines in chronic inflammatory arthritis. II. Granulocyte-macrophage colony-stimulating factor in rheumatoid synovial effusions. J Clin Invest. 1989;83:876\u201382.","journal-title":"J Clin Invest"},{"key":"1879_CR12","doi-asserted-by":"crossref","first-page":"3365","DOI":"10.4049\/jimmunol.146.10.3365","volume":"146","author":"JM Alvaro-Gracia","year":"1991","unstructured":"Alvaro-Gracia JM, Zvaifler NJ, Brown CB, Kaushansky K, Firestein GS. Cytokines in chronic inflammatory arthritis. VI. Analysis of the synovial cells involved in granulocyte-macrophage colony-stimulating factor production and gene expression in rheumatoid arthritis and its regulation by IL-1 and tumor necrosis factor-alpha. J Immunol. 1991;146:3365\u201371.","journal-title":"J Immunol"},{"key":"1879_CR13","first-page":"121","volume":"51","author":"C Fiehn","year":"1992","unstructured":"Fiehn C, Wermann M, Pezzutto A, Hufner M, Heilig B. Plasma GM-CSF concentrations in rheumatoid arthritis, systemic lupus erythematosus and spondyloarthropathy. Z Rheumatol. 1992;51:121\u20136.","journal-title":"Z Rheumatol"},{"key":"1879_CR14","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1136\/ard.54.8.654","volume":"54","author":"AK Ulfgren","year":"1995","unstructured":"Ulfgren AK, Lindblad S, Klareskog L, Andersson J, Andersson U. Detection of cytokine producing cells in the synovial membrane from patients with rheumatoid arthritis. Ann Rheum Dis. 1995;54:654\u201361.","journal-title":"Ann Rheum Dis"},{"key":"1879_CR15","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1093\/rheumatology\/31.10.653","volume":"31","author":"CQ Chu","year":"1992","unstructured":"Chu CQ, Field M, Allard S, Abney E, Feldmann M, Maini RN. Detection of cytokines at the cartilage\/pannus junction in patients with rheumatoid arthritis: implications for the role of cytokines in cartilage destruction and repair. Br J Rheumatol. 1992;31:653\u201361.","journal-title":"Br J Rheumatol"},{"key":"1879_CR16","doi-asserted-by":"crossref","first-page":"3639","DOI":"10.4049\/jimmunol.161.7.3639","volume":"161","author":"IK Campbell","year":"1998","unstructured":"Campbell IK, Rich MJ, Bischof RJ, Dunn AR, Grail D, Hamilton JA. Protection from collagen-induced arthritis in granulocyte-macrophage colony-stimulating factor-deficient mice. J Immunol. 1998;161:3639\u201344.","journal-title":"J Immunol"},{"key":"1879_CR17","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1186\/ar318","volume":"3","author":"AD Cook","year":"2001","unstructured":"Cook AD, Braine EL, Campbell IK, Rich MJ, Hamilton JA. Blockade of collagen-induced arthritis post-onset by antibody to granulocyte-macrophage colony-stimulating factor (GM-CSF): requirement for GM-CSF in the effector phase of disease. Arthritis Res. 2001;3:293\u20138.","journal-title":"Arthritis Res"},{"key":"1879_CR18","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1084\/jem.20092301","volume":"207","author":"M Hashimoto","year":"2010","unstructured":"Hashimoto M, Hirota K, Yoshitomi H, Maeda S, Teradaira S, Akizuki S, et al. Complement drives Th17 cell differentiation and triggers autoimmune arthritis. J Exp Med. 2010;207:1135\u201343.","journal-title":"J Exp Med"},{"key":"1879_CR19","doi-asserted-by":"publisher","first-page":"2340","DOI":"10.1002\/art.30354","volume":"63","author":"AD Cook","year":"2011","unstructured":"Cook AD, Turner AL, Braine EL, Pobjoy J, Lenzo JC, Hamilton JA. Regulation of systemic and local myeloid cell subpopulations by bone marrow cell-derived granulocyte-macrophage colony-stimulating factor in experimental inflammatory arthritis. Arthritis Rheum. 2011;63:2340\u201351.","journal-title":"Arthritis Rheum"},{"key":"1879_CR20","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1136\/annrheumdis-2012-201703","volume":"72","author":"AD Cook","year":"2013","unstructured":"Cook AD, Pobjoy J, Sarros S, Steidl S, Durr M, Lacey DC, et al. Granulocyte-macrophage colony-stimulating factor is a key mediator in inflammatory and arthritic pain. Ann Rheum Dis. 2013;72:265\u201370.","journal-title":"Ann Rheum Dis"},{"key":"1879_CR21","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1016\/0140-6736(91)90594-F","volume":"338","author":"EGE Vries De","year":"1991","unstructured":"De Vries EGE, Willemse PHB, Biesma B, Stern AC, Limburg PC, Vellenga E. Flare-up of rheumatoid arthritis during GM-CSF treatment after chemotherapy. Lancet. 1991;338:517\u20138.","journal-title":"Lancet"},{"key":"1879_CR22","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1182\/blood.V74.8.2769.2769","volume":"74","author":"BP Hazenberg","year":"1989","unstructured":"Hazenberg BP, Van Leeuwen MA, Van Rijswijk MH, Stern AC, Vellenga E. Correction of granulocytopenia in Felty\u2019s syndrome by granulocyte-macrophage colony-stimulating factor. Simultaneous induction of interleukin-6 release and flare-up of the arthritis. Blood. 1989;74:2769\u201370.","journal-title":"Blood"},{"key":"1879_CR23","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.1136\/ard.2010.146225","volume":"70","author":"GR Burmester","year":"2011","unstructured":"Burmester GR, Feist E, Sleeman MA, Wang B, White B, Magrini F. Mavrilimumab, a human monoclonal antibody targeting GM-CSF receptor-alpha, in subjects with rheumatoid arthritis: a randomised, double-blind, placebo-controlled, phase I, first-in-human study. Ann Rheum Dis. 2011;70:1542\u20139.","journal-title":"Ann Rheum Dis"},{"key":"1879_CR24","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1136\/annrheumdis-2012-202450","volume":"72","author":"GR Burmester","year":"2013","unstructured":"Burmester GR, Weinblatt ME, McInnes IB, Porter D, Barbarash O, Vatutin M, et al. Efficacy and safety of mavrilimumab in subjects with rheumatoid arthritis. Ann Rheum Dis. 2013;72:1445\u201352.","journal-title":"Ann Rheum Dis"},{"key":"1879_CR25","doi-asserted-by":"publisher","first-page":"21","DOI":"10.3109\/14397595.2014.896448","volume":"25","author":"T Takeuchi","year":"2015","unstructured":"Takeuchi T, Tanaka Y, Close D, Godwood A, Wu CY, Saurigny D. Efficacy and safety of mavrilimumab in Japanese subjects with rheumatoid arthritis: findings from a phase IIa study. Mod Rheumatol. 2015;25:21\u201330.","journal-title":"Mod Rheumatol"},{"issue":"abstract","key":"1879_CR26","first-page":"2821","volume":"66","author":"GR Burmester","year":"2014","unstructured":"Burmester GR, McInnes IB, Kremer JM, Miranda P, Mariusz Korkosz JV, Rubbert-Roth A, et al. Efficacy and safety\/tolerability of mavrilimumab, a human GM-CSF monoclonal antibody in patients with rheumatoid arthritis. Arthritis Rheum. 2014;66(abstract):2821.","journal-title":"Arthritis Rheum"},{"key":"1879_CR27","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1136\/annrheumdis-2013-204816","volume":"74","author":"F Behrens","year":"2015","unstructured":"Behrens F, Tak PP, Ostergaard M, Stoilov R, Wiland P, Huizinga TW, et al. MOR103, a human monoclonal antibody to granulocyte-macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib\/IIa randomised, double-blind, placebo-controlled, dose-escalation trial. Ann Rheum Dis. 2015;74:1058\u201364.","journal-title":"Ann Rheum Dis"},{"key":"1879_CR28","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1016\/j.molimm.2006.03.020","volume":"44","author":"EM Krinner","year":"2007","unstructured":"Krinner EM, Raum T, Petsch S, Bruckmaier S, Schuster I, Petersen L, et al. A human monoclonal IgG1 potently neutralizing the pro-inflammatory cytokine GM-CSF. Mol Immunol. 2007;44:916\u201325.","journal-title":"Mol Immunol"},{"key":"1879_CR29","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1136\/ard.2006.057182","volume":"66","author":"C Plater-Zyberk","year":"2007","unstructured":"Plater-Zyberk C, Joosten LA, Helsen MM, Hepp J, Baeuerle PA, van den Berg WB. GM-CSF neutralisation suppresses inflammation and protects cartilage in acute streptococcal cell wall arthritis of mice. Ann Rheum Dis. 2007;66:452\u20137.","journal-title":"Ann Rheum Dis"},{"key":"1879_CR30","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/s13075-017-1267-3","volume":"19","author":"TW Huizinga","year":"2017","unstructured":"Huizinga TW, Batalov A, Stoilov R, Lloyd E, Wagner T, Saurigny D, Souberbielle B, Esfandiari E. Phase 1b randomized, double-blind study of namilumab, an anti-granulocyte macrophage colony-stimulating factor monoclonal antibody, in mild-to-moderate rheumatoid arthritis. Arthritis Res Ther. 2017;19:53.","journal-title":"Arthritis Res Ther"},{"key":"1879_CR31","doi-asserted-by":"crossref","unstructured":"Ware JE, Kosinski M. Interpreting SF-36 summary health measures: a response. Qual Life Res. 2001;10:405\u201313.","DOI":"10.1023\/A:1012588218728"},{"key":"1879_CR32","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1164\/rccm.200708-1271OC","volume":"177","author":"Y Inoue","year":"2008","unstructured":"Inoue Y, Trapnell BC, Tazawa R, et al. Characteristics of a large cohort of patients with autoimmune pulmonary alveolar proteinosis in Japan. Am J Respir Crit Care Med. 2008;177:752\u201362.","journal-title":"Am J Respir Crit Care Med"},{"key":"1879_CR33","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, Huizinga TW, Haney DJ, Shen Y, et al. Validation of a novel multibiomarker test to assess rheumatoid arthritis disease activity. Arthritis Care Res (Hoboken). 2012;64:1794\u2013803.","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"1879_CR34","doi-asserted-by":"publisher","first-page":"R86","DOI":"10.1186\/ar4266","volume":"15","author":"AS Siebuhr","year":"2013","unstructured":"Siebuhr AS, Bay-Jensen AC, Leeming DJ, Plat A, Byrialsen I, Christiansen C, et al. Serological identification of fast progressors of structural damage with rheumatoid arthritis. Arthritis Res Ther. 2013;15:R86.","journal-title":"Arthritis Res Ther"},{"key":"1879_CR35","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1038\/clpt.2011.242","volume":"90","author":"JW Mandema","year":"2011","unstructured":"Mandema JW, Gibbs M, Boyd RA, Wada DR, Pfister M. Model-based meta-analysis for comparative efficacy and safety: application in drug development and beyond. Clin Pharmacol Ther. 2011;90:766\u20139.","journal-title":"Clin Pharmacol Ther"},{"key":"1879_CR36","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1186\/ar3080","volume":"12","author":"RB Landew\u00e9","year":"2010","unstructured":"Landew\u00e9 RB, et al. Efficacy assessed in follow-ups of clinical studies: methodological conundrum. Arthritis Res Ther. 2010;12:132.","journal-title":"Arthritis Res Ther"},{"issue":"6","key":"1879_CR37","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1136\/annrheumdis-2016-210624","volume":"76","author":"Gerd R Burmester","year":"2017","unstructured":"Burmester GR, McInnes IB, Kremer J, Miranda P, Korkosz M, Vencovsky J, et al; EARTH EXPLORER 1 Study Investigators. A randomised phase IIb study of mavrilimumab, a novel GM-CSF receptor alpha monoclonal antibody, in the treatment of rheumatoid arthritis. Ann Rheum Dis 2017;76:1020\u20131030.","journal-title":"Annals of the Rheumatic Diseases"},{"key":"1879_CR38","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1056\/NEJM200011303432201","volume":"343","author":"JM Bathon","year":"2000","unstructured":"Bathon JM, Martin RW, Fleishmann RM, Tesser JR, Schiff MH, Keystone EC, et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med. 2000;343:1586\u201393.","journal-title":"N Engl J Med"}],"container-title":["Arthritis Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-019-1879-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13075-019-1879-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-019-1879-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T21:21:39Z","timestamp":1694812899000},"score":1,"resource":{"primary":{"URL":"https:\/\/arthritis-research.biomedcentral.com\/articles\/10.1186\/s13075-019-1879-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,18]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["1879"],"URL":"https:\/\/doi.org\/10.1186\/s13075-019-1879-x","relation":{},"ISSN":["1478-6362"],"issn-type":[{"value":"1478-6362","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,18]]},"assertion":[{"value":"12 December 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 March 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 April 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Institutional review boards or ethics committees at the participating investigational centres approved the study, which was conducted according to the principles set out in the Declaration of Helsinki, International Conference on Harmonisation Guidelines for Good Clinical Practice, and additional local regulations.","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":"Dr. Wagner was an employee of Takeda Pharmaceuticals International GmbH. Both Bernard Souberbielle and Didier Saurigny were employees of Takeda at the time of the study. Barbara Hunt is an employee of Takeda International, Deerfield, IL, USA. The other authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Publisher\u2019s Note"}}],"article-number":"101"}}