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Anderson J, Caplan L, Yazdany J, et al. Rheumatoid arthritis disease activity measures: American College of Rheumatology recommendations for use in clinical practice. Arthritis Care Res (Hoboken). 2012;64:640-647.

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de Jong PH, Hazes JM, Barendregt PJ, et al. Induction therapy with a combination of DMARDs is better than methotrexate monotherapy: first results of the tREACH trial. Ann Rheum Dis. 2013;72:72-78.

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Moreland LW, O'Dell JR, Paulus HE, et al. A randomized comparative effectiveness study of oral triple therapy versus etanercept plus methotrexate in early aggressive rheumatoid arthritis: the treatment of Early Aggressive Rheumatoid Arthritis Trial. Arthritis Rheum. 2012;64:2824-2835.

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Scott DL, Ibrahim F, Farewell V, et al. Tumour necrosis factor inhibitors versus combination intensive therapy with conventional disease modifying anti-rheumatic drugs in established rheumatoid arthritis: TACIT non-inferiority randomised controlled trial. BMJ. 2015;350:h1046.

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Westhovens R, Robles M, Ximenes AC, et al. Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors. Ann Rheum Dis. 2009;68:1870-1877.

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Weinblatt ME, Schiff M, Valente R, et al. Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: findings of a phase IIIb, multinational, prospective, randomized study. Arthritis Rheum. 2013;65:28-38.

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Emery P, Burmester GR, Bykerk VP, et al. Evaluating drug-free remission with abatacept in early rheumatoid arthritis: results from the phase 3b, multicentre, randomised, active-controlled AVERT study of 24 months, with a 12-month, double-blind treatment period. Ann Rheum Dis. 2015;74:19-26.

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Dougados M, Kissel K, Sheeran T, et al. 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. 2013;72:43-50.

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Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2016;68:1-26.

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ter Wee MM, den Uyl D, Boers M, et al. Intensive combination treatment regimens, including prednisolone, are effective in treating patients with early rheumatoid arthritis regardless of additional etanercept: 1-year results of the COBRA-light open-label, randomised, non-inferiority trial. Ann Rheum Dis. 2015;74:1233-1240.

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1.  Lee DM, Weinblatt ME. Rheumatoid arthritis. Lancet. 2001;358:903-911.

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2.  Pincus T, Sokka T. How can the risk of long-term consequences of rheumatoid arthritis be reduced? Best Pract Res Clin Rheumatol. 2001;15:139-170.

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5.  Alamanos Y, Voulgari PV, Drosos AA. Incidence and prevalence of rheumatoid arthritis, based on the 1987 American College of Rheumatology criteria: a systematic review. Semin Arthritis Rheum. 2006;36:182-188.

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6.  Silman AJ. The changing face of rheumatoid arthritis: why the decline in incidence? Arthritis Rheum. 2002;46:579-581.

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8.  Kalla AA, Tikly M. Rheumatoid arthritis in the developing world. Best Pract Res Clin Rheumatol. 2003;17:863-875.

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9.  Gregersen PK, Silver J, Winchester RJ. The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum. 1987;30:1205-1213.

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10.  van der Helm-van Mil AH, Huizinga TW, de Vries RR, et al. Emerging patterns of risk factor make-up enable subclassification of rheumatoid arthritis. Arthritis Rheum. 2007;56:1728-1735.

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11.  Lee HS, Irigoyen P, Kern M, et al. Interaction between smoking, the shared epitope, and anti-cyclic citrullinated peptide: a mixed picture in three large North American rheumatoid arthritis cohorts. Arthritis Rheum. 2007;56:1745-1753.

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12.  Rakieh C, Nam JL, Hunt L, et al. Predicting the development of clinical arthritis in anti-CCP positive individuals with non-specific musculoskeletal symptoms: a prospective observational cohort study. Ann Rheum Dis. 2015;74:1659-1666.

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13.  Nam JL, Hunt L, Hensor EM, et al. Enriching case selection for imminent RA: the use of anti-CCP antibodies in individuals with new non-specific musculoskeletal symptoms - a cohort study. Ann Rheum Dis. 2016;75:1452-1456.

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14.  Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62:2569-2581.

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15.  van Gaalen FA, Linn-Rasker SP, van Venrooij WJ, et al. Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undifferentiated arthritis: a prospective cohort study. Arthritis Rheum. 2004;50:709-715.

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17.  Mohan C, Assassi S. Biomarkers in rheumatic diseases: how can they facilitate diagnosis and assessment of disease activity? BMJ. 2015;351:h5079.

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18.  van der Heijde DM, van 't Hof M, van Riel PL, et al. Development of a disease activity score based on judgment in clinical practice by rheumatologists. J Rheumatol. 1993;20:579-581.

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19.  Aletaha D, Smolen J. The Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI): a review of their usefulness and validity in rheumatoid arthritis. Clin Exp Rheumatol. 2005;23(5 Suppl 39):S100-S108.

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20.  Pincus T, Yazici Y, Bergman M, et al. A proposed approach to recognise "near-remission" quantitatively without formal joint counts or laboratory tests: a patient self-report questionnaire routine assessment of patient index data (RAPID) score as a guide to a "continuous quality improvement". Clin Exp Rheumatol. 2006;24(6 Suppl 43):S60-S65.

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21.  Anderson J, Caplan L, Yazdany J, et al. Rheumatoid arthritis disease activity measures: American College of Rheumatology recommendations for use in clinical practice. Arthritis Care Res (Hoboken). 2012;64:640-647.

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22.  Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, et al. Comparison of treatment strategies in early rheumatoid arthritis: a randomized trial. Ann Intern Med. 2007;146:406-415.

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23.  Grigor C, Capell H, Stirling A, et al. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial. Lancet. 2004;364:263-269.

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24.  Klarenbeek NB, Güler-Yüksel M, van der Kooij SM, et al. The impact of four dynamic, goal-steered treatment strategies on the 5-year outcomes of rheumatoid arthritis patients in the BeSt study. Ann Rheum Dis. 2011;70:1039-1046.

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25.  Aho K, Palusuo T, Kurki P. Marker antibodies of rheumatoid arthritis: diagnostic and pathogenetic implications. Semin Arthritis Rheum. 1994 Jun;23(6):379-87.

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26.  Goldbach-Mansky R, Lee J, McCoy A, et al. Rheumatoid arthritis associated autoantibodies in patients with synovitis of recent onset. Arthritis Res. 2000;2:236-243.

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27.  Arnett FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31:315-324.

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28.  Pincus T, Callahan LF. Taking mortality in rheumatoid arthritis seriously - predictive markers, socioeconomic status and comorbidity. J Rheumatol. 1986;13:841-845.

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29.  de Jong PH, Hazes JM, Barendregt PJ, et al. Induction therapy with a combination of DMARDs is better than methotrexate monotherapy: first results of the tREACH trial. Ann Rheum Dis. 2013;72:72-78.

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30.  van Vollenhoven RF, Ernestam S, Geborek P, et al. Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to methotrexate in patients with early rheumatoid arthritis (Swefot trial): 1-year results of a randomised trial. Lancet. 2009;374:459-466.

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31.  Bijlsma JW, Welsing PM, Woodworth TG, et al. Early rheumatoid arthritis treated with tocilizumab, methotrexate, or their combination (U-Act-Early): a multicentre, randomised, double-blind, double-dummy, strategy trial. Lancet. 2016;388:343-355.

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32.  Burmester GR, Kivitz AJ, Kupper H, et al. Efficacy and safety of ascending methotrexate dose in combination with adalimumab: the randomised CONCERTO trial. Ann Rheum Dis. 2015;74:1037-1044.

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33.  van Vollenhoven RF, Geborek P, Forslind K, et al. Conventional combination treatment versus biological treatment in methotrexate-refractory early rheumatoid arthritis: 2 year follow-up of the randomised, non-blinded, parallel-group Swefot trial. Lancet. 2012;379:1712-1720.

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34.  Singh JA, Hossain A, Tanjong Ghogomu E, et al. Biologics or tofacitinib for rheumatoid arthritis in incomplete responders to methotrexate or other traditional disease-modifying anti-rheumatic drugs: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2016;(5):CD012183.

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35.  Moreland LW, O'Dell JR, Paulus HE, et al. A randomized comparative effectiveness study of oral triple therapy versus etanercept plus methotrexate in early aggressive rheumatoid arthritis: the treatment of Early Aggressive Rheumatoid Arthritis Trial. Arthritis Rheum. 2012;64:2824-2835.

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36.  Scott DL, Ibrahim F, Farewell V, et al. Tumour necrosis factor inhibitors versus combination intensive therapy with conventional disease modifying anti-rheumatic drugs in established rheumatoid arthritis: TACIT non-inferiority randomised controlled trial. BMJ. 2015;350:h1046.

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37.  Guyot P, Taylor P, Christensen R, et al. Abatacept with methotrexate versus other biologic agents in treatment of patients with active rheumatoid arthritis despite methotrexate: a network meta-analysis. Arthritis Res Ther. 2011;13:R204.

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38.  Kremer JM, Cohen S, Wilkinson BE, et al. A phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) versus placebo in combination with background methotrexate in patients with active rheumatoid arthritis and an inadequate response to methotrexate alone. Arthritis Rheum. 2012;64:970-981.

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39.  Fleischmann R, Kremer J, Cush J, et al. Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. N Engl J Med. 2012;367:495-507.

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40.  van Vollenhoven RF, Fleischmann R, Cohen S, et al. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl J Med. 2012;367:508-519.

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41.  Breedveld FC, Weisman MH, Kavanaugh AF, et al. The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum. 2006;54:26-37.

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42.  Smolen JS, Van Der Heijde DM, St Clair EW, et al. Predictors of joint damage in patients with early rheumatoid arthritis treated with high-dose methotrexate with or without concomitant infliximab: results from the ASPIRE trial. Arthritis Rheum. 2006;54:702-710.

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43.  Klareskog L, van der Heijde D, de Jager JP, et al; TEMPO (Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes) study investigators. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet. 2004;363:675-681.

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44.  Carmona L, Ortiz A, Abad MA. How good is to switch between biologics? A systematic review of the literature. Acta Reumatol Port. 2007;32:113-128.

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45.  Gibofsky A, Yazici Y. Treatment of rheumatoid arthritis: strategies for achieving optimal outcomes. Ann Rheum Dis. 2010;69:941-942.

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46.  Smolen JS, Landewé R, Bijlsma J, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017;76:960-977.

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47.  Schmitz S, Adams R, Walsh CD, et al. A mixed treatment comparison of the efficacy of anti-TNF agents in rheumatoid arthritis for methotrexate non-responders demonstrates differences between treatments: a Bayesian approach. Ann Rheum Dis. 2012;71:225-230.

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48.  Michaud TL, Rho YH, Shamliyan T, et al. The comparative safety of tumor necrosis factor inhibitors in rheumatoid arthritis: a meta-analysis update of 44 trials. Am J Med. 2014;127:1208-1232.

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49.  Thompson AE, Rieder SW, Pope JE. Tumor necrosis factor therapy and the risk of serious infection and malignancy in patients with early rheumatoid arthritis: a meta-analysis of randomized controlled trials. Arthritis Rheum. 2011;63:1479-1485.

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50.  Mercer LK, Lunt M, Low AL, et al. Risk of solid cancer in patients exposed to anti-tumour necrosis factor therapy: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis. Ann Rheum Dis. 2015;74:1087-1093.

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51.  Westhovens R, Robles M, Ximenes AC, et al. Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors. Ann Rheum Dis. 2009;68:1870-1877.

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52.  Weinblatt ME, Schiff M, Valente R, et al. Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: findings of a phase IIIb, multinational, prospective, randomized study. Arthritis Rheum. 2013;65:28-38.

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• 摘要

53.  Emery P, Burmester GR, Bykerk VP, et al. Evaluating drug-free remission with abatacept in early rheumatoid arthritis: results from the phase 3b, multicentre, randomised, active-controlled AVERT study of 24 months, with a 12-month, double-blind treatment period. Ann Rheum Dis. 2015;74:19-26.

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54.  Westhovens R, Robles M, Ximenes AC, et al. Maintenance of remission following 2 years of standard treatment then dose reduction with abatacept in patients with early rheumatoid arthritis and poor prognosis. Ann Rheum Dis. 2015;74:564-568.

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55.  Lee EB, Fleischmann R, Hall S, et al; ORAL Start Investigators. Tofacitinib versus methotrexate in rheumatoid arthritis. N Engl J Med. 2014;370:2377-2386.

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56.  Emery P, Fleischmann R, Filipowicz-Sosnowska A, et al. The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment: results of a phase IIB randomized, double-blind, placebo-controlled, dose-ranging trial. Arthritis Rheum. 2006;54:1390-1400.

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57.  Fleischmann R, Cutolo M, Genovese MC, et al. Phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) or adalimumab monotherapy versus placebo in patients with active rheumatoid arthritis with an inadequate response to disease-modifying antirheumatic drugs. Arthritis Rheum. 2012;64:617-629.

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58.  Yazici Y, Curtis JR, Ince A, et al. Efficacy of tocilizumab in patients with moderate to severe active rheumatoid arthritis and a previous inadequate response to disease-modifying antirheumatic drugs: the ROSE study. Ann Rheum Dis. 2012;71:198-205.

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59.  Kremer JM, Blanco R, Brzosko M, et al. 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. 2011;63:609-621.

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60.  Tak PP, Rigby WF, Rubbert-Roth A, et al. Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate in early active rheumatoid arthritis: the IMAGE trial. Ann Rheum Dis. 2011;70:39-46.

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61.  Dougados M, Kissel K, Sheeran T, et al. 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. 2013;72:43-50.

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62.  van Herwaarden N, van der Maas A, Minten MJ, et al. Disease activity guided dose reduction and withdrawal of adalimumab or etanercept compared with usual care in rheumatoid arthritis: open label, randomised controlled, non-inferiority trial. BMJ. 2015;350:h1389.

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63.  Fautrel B, Pham T, Alfaiate T, et al. Step-down strategy of spacing TNF-blocker injections for established rheumatoid arthritis in remission: results of the multicentre non-inferiority randomised open-label controlled trial (STRASS: Spacing of TNF-blocker injections in Rheumatoid ArthritiS Study). Ann Rheum Dis. 2016;75:59-67.

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64.  Kuijper TM, Lamers-Karnebeek FB, Jacobs JW, et al. Flare rate in patients with rheumatoid arthritis in low disease activity or remission when tapering or stopping synthetic or biologic DMARD: a systematic review. J Rheumatol. 2015;42:2012-2022.

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65.  van Vollenhoven RF, Østergaard M, Leirisalo-Repo M, et al. Full dose, reduced dose or discontinuation of etanercept in rheumatoid arthritis. Ann Rheum Dis. 2016;75:52-58.

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66.  Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2016;68:1-26.

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67.  ter Wee MM, den Uyl D, Boers M, et al. Intensive combination treatment regimens, including prednisolone, are effective in treating patients with early rheumatoid arthritis regardless of additional etanercept: 1-year results of the COBRA-light open-label, randomised, non-inferiority trial. Ann Rheum Dis. 2015;74:1233-1240.

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68.  van Everdingen AA, Jacobs JW, Siewertsz Van Reesema DR, et al. Low-dose prednisone therapy for patients with early active rheumatoid arthritis: clinical efficacy, disease-modifying properties, and side effects: a randomized, double-blind, placebo-controlled clinical trial. Ann Intern Med. 2002;136:1-12.

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69.  Pincus T, Huizinga TW, Yazici Y. N-of-1 trial of low-dose methotrexate and/or prednisolone in lieu of anti-CCP, MRI, or ultrasound, as first option in suspected rheumatoid arthritis? J Rheumatol. 2007;34:250-252.

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70.  Pincus T, Sokka T, Stein CM. Are long-term very low doses of prednisone for patients with rheumatoid arthritis as helpful as high doses are harmful? Ann Intern Med. 2002;136:76-78.

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74.  Verschueren P, De Cock D, Corluy L, et al. Methotrexate in combination with other DMARDs is not superior to methotrexate alone for remission induction with moderate-to-high-dose glucocorticoid bridging in early rheumatoid arthritis after 16 weeks of treatment: the CareRA trial. Ann Rheum Dis. 2015;74:27-34.

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75.  Buttgereit F, Mehta D, Kirwan J, et al. Low-dose prednisone chronotherapy for rheumatoid arthritis: a randomised clinical trial (CAPRA-2). Ann Rheum Dis. 2013;72:204-210.

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76.  Ostensen M, Villiger PM. The remission of rheumatoid arthritis during pregnancy. Semin Immunopathol. 2007;29:185-191.

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77.  Genovese MC, Fleischmann R, Kivitz AJ, et al. Sarilumab plus methotrexate in patients with active rheumatoid arthritis and inadequate response to methotrexate: results of a phase III study. Arthritis Rheumatol. 2015;67:1424-1437.

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78.  Huizinga TW, Fleischmann RM, Jasson M, et al. Sarilumab, a fully human monoclonal antibody against IL-6Rα in patients with rheumatoid arthritis and an inadequate response to methotrexate: efficacy and safety results from the randomised SARIL-RA-MOBILITY Part A trial. Ann Rheum Dis. 2014;73:1626-1634.

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81.  Genovese MC, Kremer J, Zamani O, et al. Baricitinib in patients with refractory rheumatoid arthritis. N Engl J Med. 2016;374:1243-1252.

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82.  Dougados M, van der Heijde D, Chen YC, et al. Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: results from the RA-BUILD study. Ann Rheum Dis. 2017;76:88-95.

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83.  National Institute for Health and Care Excellence. Baricitinib for moderate to severe rheumatoid arthritis. Technology appraisal guidance [TA466]. August 2017. https://www.nice.org.uk/ (last accessed 11 August 2017).

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85.  Henaux S, Ruyssen-Witrand A, Cantagrel A, et al. Risk of losing remission, low disease activity or radiographic progression in case of bDMARD discontinuation or tapering in rheumatoid arthritis: systematic analysis of the literature and meta-analysis. Ann Rheum Dis. 2017 Nov 29. pii: annrheumdis-2017-212423.

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87.  Pincus T, Sokka T. Complexities in the quantitative assessment of patients with rheumatic diseases in clinical trials and clinical care. Clin Exp Rheumatol. 2005;23(5 Suppl 39):S1-S9.

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88.  Aletaha D, Smolen JS. The Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) to monitor patients in standard clinical care. Best Pract Res Clin Rheumatol. 2007;21:663-675.

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