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Why did IL-23p19 inhibition fail i\ n AS: a tale of tissues, trials \nor translation? Ann. Rheum. Dis. 78, 1015 1018 \(2019\).\r:84)/F 4/H/N/Rect[246.305 620.855 251.4 608.444]/Subtype/Link/Type/Annot>> endobj 117 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevImmun_603.indd:38. Sepriano, A. etal. Safety of synthetic and biological DMARDs: a systematic li\ terature review informing \nthe 2019 update of the EULAR recommendations for \nthe management of rheumatoid arthritis. Ann. Rheu\ m. Dis. 79, 760 770 \(2020\).\r:85)/F 4/H/N/Rect[290.509 433.855 295.605 421.444]/Subtype/Link/Type/Annot>> endobj 118 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevImmun_603.indd:39. Sbidian, E. etal. Systemic pharmacological treatments for chronic plaque psor\ iasis: a network meta- analysis. Cochrane Database Syst. 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Bimekizumab in patients with active psoriatic arthritis\ : results from a 48-week, randomised, double- blind, placebo- controlled, dose-ranging phase 2b trial. Lancet 395, 427 440 \(\ 2020\).\r:89)/F 4/H/N/Rect[359.158 180.855 364.254 168.444]/Subtype/Link/Type/Annot>> endobj 122 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevImmun_603.indd:30. Nash, P. etal. Points to consider for the treatment of immune- mediated inf\ lammatory diseases with Janus kinase inhibitors: a consensus statement. Ann. Rheum. Dis. 80, 71 87 \(2021\).\r:90)/F 4/H/N/Rect[303.208 103.855 308.304 91.4439]/Subtype/Link/Type/Annot>> endobj 123 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevImmun_603.indd:33. McInnes, I. B. & Schett, G. Pathogenetic insights from the treatment of rheum\ atoid arthritis. Lancet 389, 2328 2337 \(2017\).\r:91)/F 4/H/N/Rect[433.071 532.855 438.166 520.444]/Subtype/Link/Type/Annot>> endobj 124 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevImmun_603.indd:43. McInnes, I. B. etal. Effect of interleukin-6 receptor blockade on surrogates \ of vascular risk in rheumatoid arthritis: MEASURE, a randomised, placebo- controlled study. Ann. Rheum. Dis. 74, 694 702 \(2\ 015\).\r:92)/F 4/H/N/Rect[439.362 532.855 444.457 520.444]/Subtype/Link/Type/Annot>> endobj 125 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevImmun_603.indd:44. Budu- Aggrey, A. etal. Evidence of a causal relationship between body mass in\ dex and psoriasis: a Mendelian randomization study. PLoS Med. 16, e1002739 \(2019\).\r:93)/F 4/H/N/Rect[473.071 455.855 478.166 443.444]/Subtype/Link/Type/Annot>> endobj 126 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevImmun_603.indd:45. Aksentijevich, M., Lateef, S. S., Anzenberg, P., \nDey, A. K. & Mehta, N. N. Ch\ ronic inflammation, cardiometabolic diseases and effects of treatment: psoriasis as a human model. Trends Cardiovasc. Med. 3\ 0, 472 478 \(2020\).\r:94)/F 4/H/N/Rect[511.158 389.855 516.253 377.444]/Subtype/Link/Type/Annot>> endobj 127 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevImmun_603.indd:46. Ridker, P. M. etal. Antiinflammatory therapy with canakinumab for atheroscler\ otic disease. N. Engl. \nJ. Med. 377, 1119 1131 \(2017\).\r:95)/F 4/H/N/Rect[454.936 323.855 460.031 311.444]/Subtype/Link/Type/Annot>> endobj 128 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevImmun_603.indd:47. Schrepf, A. etal. A multi- modal MRI study of the central response to inflamm\ ation in rheumatoid arthritis. Nat. 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Mosanya, C. H. & Isaacs, J. D. Tolerising cellular therapies: what is their pr\ omise for autoimmune disease? Ann. Rheum. Dis. 78, 297 310 \(2019\).\r:97)/F 4/H/N/Rect[142.107 554.855 147.181 542.444]/Subtype/Link/Type/Annot>> endobj 134 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevImmun_603.indd:49. Bluestone, J. A. & Anderson, M. Tolerance in the age of immunotherapy. N. Eng\ l. J. Med. 383, 1156 1166 \(2020\).\r:98)/F 4/H/N/Rect[148.366 554.855 153.44 542.444]/Subtype/Link/Type/Annot>> endobj 135 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevImmun_603.indd:50. Koopman, F. A. etal. Vagus nerve stimulation inhibits cytokine production and\ attenuates disease severity in rheumatoid arthritis. Proc. Natl Acad. Sci. USA 113, 8284 8289 \(2016\).\r:99)/F 4/H/N/Rect[164.385 510.855 169.459 498.444]/Subtype/Link/Type/Annot>> endobj 136 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevImmun_603.indd:Fig. 3 | Future approaches for immune-mediated inflammatory disease therapeutics\ . We envisage future therapeutic design for immune- mediated inflammatory diseases to involve a combination of routes for ca\ ndidate target discovery: kinome inte:100)/F 4/H/N/Rect[111.199 488.855 115.595 476.444]/Subtype/Link/Type/Annot>> endobj 137 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevImmun_603.indd:51. Rao, D. A. etal. Pathologically expanded peripheral \nT helper cell subset dri\ ves B cells in rheumatoid arthritis. Nature 542, 110 114 \(2017\).\r:101)/F 4/H/N/Rect[296.185 653.855 301.281 641.444]/Subtype/Link/Type/Annot>> endobj 138 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevImmun_603.indd:52. Croft, A. P. etal. Distinct fibroblast subsets drive inflammation and damage \ in arthritis. 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Gravallese 10.1038/s41577-021-00603-1 http://dx.doi.org/10.1038/s41577-021-00603-1 journal Nature Reviews Immunology © 2021, Springer Nature Limited 1474-1741 10.1038/s41577-021-00603-1 springer.com springerlink.com 2010-04-23 True 10.1038/s41577-021-00603-1 springer.com springerlink.com Springer 2021-09-22T11:09:03+05:30 2021-09-22T11:07:55+05:30 2021-09-22T11:09:03+05:30 True VoR uuid:ec15fa3c-934e-476e-89a8-ecf17bd9d7f5 uuid:eb9c3961-374d-4584-b2d8-4791501cce02 default 1 converted uuid:0ea1c6bf-d363-4099-8fb4-a3d037bb6482 converted to PDF/A-2b pdfToolbox 2021-09-22T11:09:03+05:30 2 B Iain B. McInnes http://orcid.org/0000-0003-4449-8501 http://ns.adobe.com/pdf/1.3/ pdf Adobe PDF Schema internal A name object indicating whether the document has been modified to include trapping information Trapped Text http://ns.adobe.com/pdfx/1.3/ pdfx pdfx internal ID of PDF/X standard GTS_PDFXVersion Text internal Conformance level of PDF/X standard GTS_PDFXConformance Text internal Company creating the PDF Company Text internal Date when document was last modified SourceModified Text external Mirrors crossmark:CrosMarkDomains CrossMarkDomains Seq Text internal Mirrors crossmark:DOI doi Text http://ns.adobe.com/xap/1.0/mm/ xmpMM XMP Media Management Schema internal UUID based identifier for specific incarnation of a document InstanceID URI internal The common identifier for all versions and renditions of a document. 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Burmester, G. R. & Emmrich, F. Anti- CD4 therapy \nin rheumatoid arthritis. Cli\ n. Exp. Rheumatol. 2, 627 642 \(1993\).\r:43)/F 4/H/N/Rect[62.6303 675.855 65.1833 663.444]/Subtype/Link/Type/Annot>> endobj 4 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevImmun_603.indd:7. Isaacs, J. D. etal. CAMPATH-1H in rheumatoid arthritis  an intravenous dose- \ ranging study. Br. J. Rheumatol. 35, 231 240 \(1996\).\r:44)/F 4/H/N/Rect[66.3848 675.855 68.9378 663.444]/Subtype/Link/Type/Annot>> endobj 5 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevImmun_603.indd:8. Jendro, M. C., Ganten, T., Matteson, E., Weyand, C. \n& Goronzy, J. J. Emergence\ of oligoclonal Tcell populations following therapeutic Tcell depletion in rheumatoid arthritis. Arthritis Rheum. 38, 124\ 2 1251 \(1995\).\r:45)/F 4/H/N/Rect[163.573 609.855 166.126 597.444]/Subtype/Link/Type/Annot>> endobj 6 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevImmun_603.indd:9. Ruderman, E. M., Weinblatt, M. E., Thurmond, L. M., Pinkus, G. M. & Gravallese,\ E. M. Synovial tissue response to treatment with Campath 1-H. Arthritis Rheum. 38, 254 258 \(1995\).\r:46)/F 4/H/N/Rect[167.327 609.855 169.88 597.444]/Subtype/Link/Type/Annot>> endobj 7 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevImmun_603.indd:2. Maini, R. etal. Infliximab \(chimeric anti- tumour necrosis factor alpha monoc\ lonal antibody\) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III tria\ l. Lancet 354, 1932 1939 \(1999\).\r:47)/F 4/H/N/Rect[170.681 400.855 173.234 388.444]/Subtype/Link/Type/Annot>> endobj 8 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevImmun_603.indd:3. Feldmann, M., Brennan, F. M. & Maini, R. N. Rheumatoid arthritis. Cell 85,\ 307 310 \(1996\).\r:48)/F 4/H/N/Rect[174.436 400.855 176.989 388.444]/Subtype/Link/Type/Annot>> endobj 9 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevImmun_603.indd:10. Bresnihan, B. etal. 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Schett, G., Elewaut, D., McInnes, I. B., Dayer, J. M. \n& Neurath, M. F. How cy\ tokine networks fuel inflammation: toward a cytokine- based disease taxonomy. Nat. Med. 19, 822 824 \(2013\).\r:58)/F 4/H/N/Rect[253.137 224.855 258.233 212.444]/Subtype/Link/Type/Annot>> endobj 18 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevImmun_603.indd:5. Smolen, J. S. etal. Treating rheumatoid arthritis to target: recommendations \ of an international task force. Ann. Rheum. Dis. 69, 631 637 \(2010\).\r:59)/F 4/H/N/Rect[294.389 114.855 296.937 102.444]/Subtype/Link/Type/Annot>> endobj 19 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevImmun_603.indd:20. Grigor, C. etal. Effect of a treatment strategy of tight control for rheumato\ id arthritis \(the TICORA study\): \na single- blind randomised controlled trial. 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