期刊论文详细信息
BMC Medicine
Old drugs, old problems: where do we stand in prediction of rheumatoid arthritis responsiveness to methotrexate and other synthetic DMARDs?
João Eurico Fonseca1  Helena Canhão1  Vasco Crispim Romão1 
[1] Rheumatology Department, Lisbon Academic Medical Centre, Av. Prof. Egas Moniz, Lisboa 1649-028, Portugal
关键词: Methotrexate;    Synthetic DMARDs;    Rheumatoid arthritis;    Predictors of response;   
Others  :  857217
DOI  :  10.1186/1741-7015-11-17
 received in 2012-09-05, accepted in 2013-01-23,  发布年份 2013
PDF
【 摘 要 】

Methotrexate (MTX) is the central drug in the management of rheumatoid arthritis (RA) and other immune mediated inflammatory diseases. It is widely used either in monotherapy or in association with other synthetic and biologic disease modifying anti-rheumatic drugs (DMARDs). Although comprehensive clinical experience exists for MTX and synthetic DMARDs, to date it has not been possible to preview correctly whether or not a patient will respond to treatment with these drugs. Predicting response to MTX and other DMARDs would allow the selection of patients based on their likelihood of response, thus enabling individualized therapy and avoiding unnecessary adverse effects and elevated costs. However, studies analyzing this issue have struggled to obtain consistent, replicable results and no factor has yet been recognized to individually distinguish responders from nonresponders at treatment start. Variables possibly influencing drug effectiveness may be disease-, patient- or treatment-related, clinical or biological (genetic and nongenetic). In this review we summarize current evidence on predictors of response to MTX and other synthetic DMARDs, discuss possible causes for the heterogeneity observed and address its translation into daily clinical practice.

【 授权许可】

   
2013 Romão et al; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20140723072322992.pdf 702KB PDF download
64KB Image download
【 图 表 】

【 参考文献 】
  • [1]Aletaha D, Smolen JS: The rheumatoid arthritis patient in the clinic: comparing more than 1,300 consecutive DMARD courses. Rheumatology (Oxford) 2002, 41:1367-1374.
  • [2]Sokka T, Pincus T: Contemporary disease modifying antirheumatic drugs (DMARD) in patients with recent onset rheumatoid arthritis in a US private practice: methotrexate as the anchor drug in 90% and new DMARD in 30% of patients. J Rheumatol 2002, 29:2521-2524.
  • [3]Kinder AJ, Hassell AB, Brand J, Brownfield A, Grove M, Shadforth MF: The treatment of inflammatory arthritis with methotrexate in clinical practice: treatment duration and incidence of adverse drug reactions. Rheumatology (Oxford) 2005, 44:61-66.
  • [4]Aletaha D, Smolen JS: Effectiveness profiles and dose dependent retention of traditional disease modifying antirheumatic drugs for rheumatoid arthritis. An observational study. J Rheumatol 2002, 29:1631-1638.
  • [5]Maetzel A, Wong A, Strand V, Tugwell P, Wells G, Bombardier C: Meta-analysis of treatment termination rates among rheumatoid arthritis patients receiving disease-modifying anti-rheumatic drugs. Rheumatology (Oxford) 2000, 39:975-981.
  • [6]Fonseca JE, Viana Queiroz M: Estudo da eficácia, tolerância e aceitabilidade da terapêutica da artrite reumatóide com metotrexato - experiência dos últimos 10 anos. Boletim CIAR 1997, (VII):83-88.
  • [7]Kremer JM, Genovese MC, Cannon GW, Caldwell JR, Cush JJ, Furst DE, Luggen ME, Keystone E, Weisman MH, Bensen WM, Kaine JL, Ruderman EM, Coleman P, Curtis DL, Kopp EJ, Kantor SM, Waltuck J, Lindsley HB, Markenson JA, Strand V, Crawford B, Fernando I, Simpson K, Bathon JM: Concomitant leflunomide therapy in patients with active rheumatoid arthritis despite stable doses of methotrexate. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 2002, 137:726-733.
  • [8]Mourao AF, Fonseca JE, Canhao H, Santos MJ, Bernardo A, Cordeiro A, Cravo AR, Ribeiro A, Teixeira A, Barcelos A, Malcata A, Faustino A, Duarte C, Ribeiro C, Nour D, Araujo D, Sousa E, Mariz E, Ramos F, Vinagre F, Ventura FS, Sequeira G, Santos H, Branco JC, Gomes JA, Silva JA, Ramos J, Santo JE, Costa JA, Silva JA, et al.: [Practical guide for the use of biological agents in rheumatoid arthritis - December 2011 update]. Acta Reumatol Port 2011, 36:389-395.
  • [9]Mourao AF, Canhao H, Moura RA, Cascao R, Weinmann P, Rodrigues A, Polido-Pereira J, Resende C, Capela S, Silva JA, Fonseca JE: Markers of progression to rheumatoid arthritis: discriminative value of the new ACR/EULAR rheumatoid arthritis criteria in a Portuguese population with early polyarthritis. Acta Reumatol Port 2011, 36:370-376.
  • [10]Visser K, Katchamart W, Loza E, Martinez-Lopez JA, Salliot C, Trudeau J, Bombardier C, Carmona L, van der Heijde D, Bijlsma JW, Boumpas DT, Canhao H, Edwards CJ, Hamuryudan V, Kvien TK, Leeb BF, Martin-Mola EM, Mielants H, Muller-Ladner U, Murphy G, Ostergaard M, Pereira IA, Ramos-Remus C, Valentini G, Zochling J, Dougados M: Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative. Ann Rheum Dis 2009, 68:1086-1093.
  • [11]Weinblatt ME, Kaplan H, Germain BF, Block S, Solomon SD, Merriman RC, Wolfe F, Wall B, Anderson L, Gall E, Torretti D, Weissman B: Methotrexate in rheumatoid arthritis. A five-year prospective multicenter study. Arthritis Rheum 1994, 37:1492-1498.
  • [12]O'Dell JR: Therapeutic strategies for rheumatoid arthritis. N Engl J Med 2004, 350:2591-2602.
  • [13]Machold KP, Stamm TA, Nell VP, Pflugbeil S, Aletaha D, Steiner G, Uffmann M, Smolen JS: Very recent onset rheumatoid arthritis: clinical and serological patient characteristics associated with radiographic progression over the first years of disease. Rheumatology (Oxford) 2007, 46:342-349.
  • [14]Hider SL, Silman AJ, Thomson W, Lunt M, Bunn D, Symmons DP: Can clinical factors at presentation be used to predict outcome of treatment with methotrexate in patients with early inflammatory polyarthritis? Ann Rheum Dis 2009, 68:57-62.
  • [15]Drouin J, Haraoui B: Predictors of clinical response and radiographic progression in patients with rheumatoid arthritis treated with methotrexate monotherapy. J Rheumatol 2010, 37:1405-1410.
  • [16]Hider SL, Buckley C, Silman AJ, Symmons DP, Bruce IN: Factors influencing response to disease modifying antirheumatic drugs in patients with rheumatoid arthritis. J Rheumatol 2005, 32:11-16.
  • [17]Ranganathan P: The challenges of methotrexate pharmacogenetics in rheumatoid arthritis. Pharmacogenomics 2012, 13:377.
  • [18]Bansard C, Lequerre T, Daveau M, Boyer O, Tron F, Salier JP, Vittecoq O, Le-Loet X: Can rheumatoid arthritis responsiveness to methotrexate and biologics be predicted? Rheumatology (Oxford) 2009, 48:1021-1028.
  • [19]Scherer HU, Dorner T, Burmester GR: Patient-tailored therapy in rheumatoid arthritis: an editorial review. Curr Opin Rheumatol 2010, 22:237-245.
  • [20]Polido-Pereira J, Vieira-Sousa E, Fonseca JE: Rheumatoid arthritis: what is refractory disease and how to manage it? Autoimmun Rev 2011, 10:707-713.
  • [21]Guidelines for the management of rheumatoid arthritis: 2002 Update Arthritis Rheum 2002, 46:328-346.
  • [22]Wessels JA, van der Kooij SM, le Cessie S, Kievit W, Barerra P, Allaart CF, Huizinga TW, Guchelaar HJ: A clinical pharmacogenetic model to predict the efficacy of methotrexate monotherapy in recent-onset rheumatoid arthritis. Arthritis Rheum 2007, 56:1765-1775.
  • [23]Hoekstra M, van Ede AE, Haagsma CJ, van de Laar MA, Huizinga TW, Kruijsen MW, Laan RF: Factors associated with toxicity, final dose, and efficacy of methotrexate in patients with rheumatoid arthritis. Ann Rheum Dis 2003, 62:423-426.
  • [24]Anderson JJ, Wells G, Verhoeven AC, Felson DT: Factors predicting response to treatment in rheumatoid arthritis: the importance of disease duration. Arthritis Rheum 2000, 43:22-29.
  • [25]Saevarsdottir S, Wallin H, Seddighzadeh M, Ernestam S, Geborek P, Petersson IF, Bratt J, van Vollenhoven RF: Predictors of response to methotrexate in early DMARD naive rheumatoid arthritis: results from the initial open-label phase of the SWEFOT trial. Ann Rheum Dis 2011, 70:469-475.
  • [26]Stranzl T, Wolf J, Leeb BF, Smolen JS, Pirker R, Filipits M: Expression of folylpolyglutamyl synthetase predicts poor response to methotrexate therapy in patients with rheumatoid arthritis. Clin Exp Rheumatol 2003, 21:27-32.
  • [27]Vazquez I, Graell E, Gratacos J, Canete JD, Vinas O, Ercilla MG, Gomez A, Hernandez MV, Rodriguez-Cros JR, Larrosa M, Sanmarti R: Prognostic markers of clinical remission in early rheumatoid arthritis after two years of DMARDs in a clinical setting. Clin Exp Rheumatol 2007, 25:231-238.
  • [28]Maillefert JF, Puechal X, Falgarone G, Lizard G, Ornetti P, Solau E, Legre V, Liote F, Sibilia J, Morel J, Maynadie M: Prediction of response to disease modifying antirheumatic drugs in rheumatoid arthritis. Joint Bone Spine 2010, 77:558-563.
  • [29]Ma MH, Ibrahim F, Walker D, Hassell A, Choy EH, Kiely PD, Williams R, Walsh DA, Young A, Scott DL: Remission in early rheumatoid arthritis: predicting treatment response. J Rheumatol 2012, 39:470-475.
  • [30]Choy EH, Smith CM, Farewell V, Walker D, Hassell A, Chau L, Scott DL: Factorial randomised controlled trial of glucocorticoids and combination disease modifying drugs in early rheumatoid arthritis. Ann Rheum Dis 2008, 67:656-663.
  • [31]Kiely P, Williams R, Walsh D, Young A: Contemporary patterns of care and disease activity outcome in early rheumatoid arthritis: the ERAN cohort. Rheumatology (Oxford) 2009, 48:57-60.
  • [32]Capell HA, Porter DR, Madhok R, Hunter JA: Second line (disease modifying) treatment in rheumatoid arthritis: which drug for which patient? Ann Rheum Dis 1993, 52:423-428.
  • [33]Situnayake RD, McConkey B: Clinical and laboratory effects of prolonged therapy with sulfasalazine, gold or penicillamine: the effects of disease duration on treatment response. J Rheumatol 1990, 17:1268-1273.
  • [34]Matteson EL, Weyand CM, Fulbright JW, Christianson TJ, McClelland RL, Goronzy JJ: How aggressive should initial therapy for rheumatoid arthritis be? Factors associated with response to 'non-aggressive' DMARD treatment and perspective from a 2-yr open label trial. Rheumatology (Oxford) 2004, 43:619-625.
  • [35]van den Borne BE, Landewe RB, Rietveld JH, Goei The HS, Griep EN, Breedveld FC, Dijkmans BA: Chloroquine therapy in patients with recent-onset rheumatoid arthritis: the clinical response can be predicted by the low level of acute-phase reaction at baseline. Clin Rheumatol 1999, 18:369-372.
  • [36]van Roon EN, Hoekstra M, Tobi H, Jansen TL, Bernelot Moens HJ, Brouwers JR, van de Laar MA: Leflunomide in the treatment of rheumatoid arthritis. An analysis of predictors for treatment continuation. Br J Clin Pharmacol 2005, 60:319-325.
  • [37]Mottonen T, Hannonen P, Korpela M, Nissila M, Kautiainen H, Ilonen J, Laasonen L, Kaipiainen-Seppanen O, Franzen P, Helve T, Koski J, Gripenberg-Gahmberg M, Myllykangas-Luosujarvi R, Leirisalo-Repo M: Delay to institution of therapy and induction of remission using single-drug or combination-disease-modifying antirheumatic drug therapy in early rheumatoid arthritis. Arthritis Rheum 2002, 46:894-898.
  • [38]Scott DL: The diagnosis and prognosis of early arthritis: rationale for new prognostic criteria. Arthritis Rheum 2002, 46:286-290.
  • [39]The effect of age and renal function on the efficacy and toxicity of methotrexate in rheumatoid arthritis. Rheumatoid Arthritis Clinical Trial Archive Group J Rheumatol 1995, 22:218-223.
  • [40]Bologna C, Viu P, Jorgensen C, Sany J: Effect of age on the efficacy and tolerance of methotrexate in rheumatoid arthritis. Br J Rheumatol 1996, 35:453-457.
  • [41]Wolfe F, Cathey MA: The effect of age on methotrexate efficacy and toxicity. J Rheumatol 1991, 18:973-977.
  • [42]Combe B, Cantagrel A, Goupille P, Bozonnat MC, Sibilia J, Eliaou JF, Meyer O, Sany J, Dubois A, Daures JP, Dougados M: Predictive factors of 5-year health assessment questionnaire disability in early rheumatoid arthritis. J Rheumatol 2003, 30:2344-2349.
  • [43]Helliwell PS, Ibrahim G: Ethnic differences in responses to disease modifying drugs. Rheumatology (Oxford) 2003, 42:1197-1201.
  • [44]Criswell LA, Lum RF, Turner KN, Woehl B, Zhu Y, Wang J, Tiwari HK, Edberg JC, Kimberly RP, Moreland LW, Seldin MF, Bridges SL: The influence of genetic variation in the HLA-DRB1 and LTA-TNF regions on the response to treatment of early rheumatoid arthritis with methotrexate or etanercept. Arthritis Rheum 2004, 50:2750-2756.
  • [45]Hodkinson B, Musenge E, Ally M, Meyer PW, Anderson R, Tikly M: Response to traditional disease-modifying anti-rheumatic drugs in indigent South Africans with early rheumatoid arthritis. Clin Rheumatol 2011, 31:613-619.
  • [46]Papadopoulos NG, Alamanos Y, Voulgari PV, Epagelis EK, Tsifetaki N, Drosos AA: Does cigarette smoking influence disease expression, activity and severity in early rheumatoid arthritis patients? Clin Exp Rheumatol 2005, 23:861-866.
  • [47]Manfredsdottir VF, Vikingsdottir T, Jonsson T, Geirsson AJ, Kjartansson O, Heimisdottir M, Sigurdardottir SL, Valdimarsson H, Vikingsson A: The effects of tobacco smoking and rheumatoid factor seropositivity on disease activity and joint damage in early rheumatoid arthritis. Rheumatology (Oxford) 2006, 45:734-740.
  • [48]Saag KG, Cerhan JR, Kolluri S, Ohashi K, Hunninghake GW, Schwartz DA: Cigarette smoking and rheumatoid arthritis severity. Ann Rheum Dis 1997, 56:463-469.
  • [49]Wolfe F: The effect of smoking on clinical, laboratory, and radiographic status in rheumatoid arthritis. J Rheumatol 2000, 27:630-637.
  • [50]Saevarsdottir S, Wedren S, Seddighzadeh M, Bengtsson C, Wesley A, Lindblad S, Askling J, Alfredsson L, Klareskog L: Patients with early rheumatoid arthritis who smoke are less likely to respond to treatment with methotrexate and tumor necrosis factor inhibitors: observations from the Epidemiological Investigation of Rheumatoid Arthritis and the Swedish Rheumatology Register cohorts. Arthritis Rheum 2011, 63:26-36.
  • [51]Westhoff G, Rau R, Zink A: Rheumatoid arthritis patients who smoke have a higher need for DMARDs and feel worse, but they do not have more joint damage than non-smokers of the same serological group. Rheumatology (Oxford) 2008, 47:849-854.
  • [52]Stamp LK, O'Donnell JL, Chapman PT, Zhang M, Frampton C, James J, Barclay ML: Determinants of red blood cell methotrexate polyglutamate concentrations in rheumatoid arthritis patients receiving long-term methotrexate treatment. Arthritis Rheum 2009, 60:2248-2256.
  • [53]Maradit-Kremers H, Nicola PJ, Crowson CS, O'Fallon WM, Gabriel SE: Patient, disease, and therapy-related factors that influence discontinuation of disease-modifying antirheumatic drugs: a population-based incidence cohort of patients with rheumatoid arthritis. J Rheumatol 2006, 33:248-255.
  • [54]Fonseca JE, Canhao H, Teixeira da CJ, Pereira da SJ, Queiroz MV: Global functional status in rheumatoid arthritis: disease duration and patient age. Clin Rheumatol 2002, 21:32-34.
  • [55]O'Dell JR, Nepom BS, Haire C, Gersuk VH, Gaur L, Moore GF, Drymalski W, Palmer W, Eckhoff PJ, Klassen LW, Wees S, Thiele G, Nepom GT: HLA-DRB1 typing in rheumatoid arthritis: predicting response to specific treatments. Ann Rheum Dis 1998, 57:209-213.
  • [56]Wolfe F, Hawley DJ, Cathey MA: Termination of slow acting antirheumatic therapy in rheumatoid arthritis: a 14-year prospective evaluation of 1017 consecutive starts. J Rheumatol 1990, 17:994-1002.
  • [57]O'Dell JR, Haire CE, Erikson N, Drymalski W, Palmer W, Eckhoff PJ, Garwood V, Maloley P, Klassen LW, Wees S, Klein H, Moore GF: Treatment of rheumatoid arthritis with methotrexate alone, sulfasalazine and hydroxychloroquine, or a combination of all three medications. N Engl J Med 1996, 334:1287-1291.
  • [58]Egsmose C, Lund B, Borg G, Pettersson H, Berg E, Brodin U, Trang L: Patients with rheumatoid arthritis benefit from early 2nd line therapy: 5 year followup of a prospective double blind placebo controlled study. J Rheumatol 1995, 22:2208-2213.
  • [59]Munro R, Hampson R, McEntegart A, Thomson EA, Madhok R, Capell H: Improved functional outcome in patients with early rheumatoid arthritis treated with intramuscular gold: results of a five year prospective study. Ann Rheum Dis 1998, 57:88-93.
  • [60]van der Heide A, Jacobs JW, Bijlsma JW, Heurkens AH, van Booma-Frankfort C, van der Veen MJ, Haanen HC, Hofman DM, van Albada-Kuipers GA, ter Borg EJ, Brus HL, Dinant HJ, Kruize AA, Schenk Y: The effectiveness of early treatment with "second-line" antirheumatic drugs. A randomized, controlled trial. Ann Intern Med 1996, 124:699-707.
  • [61]Tsakonas E, Fitzgerald AA, Fitzcharles MA, Cividino A, Thorne JC, M'Seffar A, Joseph L, Bombardier C, Esdaile JM: Consequences of delayed therapy with second-line agents in rheumatoid arthritis: a 3 year followup on the hydroxychloroquine in early rheumatoid arthritis (HERA) study. J Rheumatol 2000, 27:623-629.
  • [62]Cush JJ: Early rheumatoid arthritis -- is there a window of opportunity? J Rheumatol Suppl 2007, 80:1-7.
  • [63]Emery P: Early rheumatoid arthritis: therapeutic strategies. Scand J Rheumatol Suppl 1994, 100:3-7.
  • [64]Emery P: Evidence supporting the benefit of early intervention in rheumatoid arthritis. J Rheumatol Suppl 2002, 66:3-8.
  • [65]Wijnands MJ, van't Hof MA, van Leeuwen MA, van Rijswijk MH, van de Putte LB, van Riel PL: Long-term second-line treatment: a prospective drug survival study. Br J Rheumatol 1992, 31:253-258.
  • [66]Lie E, Heiberg M, Nordvag B, Rodevand E, Kaufmann C, Mikkelsen K, Kvien TK: Predictors of response to methotrexate treatment: results from a longitudinal observational study of 876 patients with RA. Ann Rheum Dis 2006, 65(Suppl II):342.
  • [67]Fries JF, Williams CA, Singh G, Ramey DR: Response to therapy in rheumatoid arthritis is influenced by immediately prior therapy. J Rheumatol 1997, 24:838-844.
  • [68]Aletaha D, Funovits J, Keystone EC, Smolen JS: Disease activity early in the course of treatment predicts response to therapy after one year in rheumatoid arthritis patients. Arthritis Rheum 2007, 56:3226-3235.
  • [69]Svensson B, Schaufelberger C, Teleman A, Theander J: Remission and response to early treatment of RA assessed by the Disease Activity Score. BARFOT study group. Better Anti-rheumatic Farmacotherapy. Rheumatology (Oxford) 2000, 39:1031-1036.
  • [70]Gossec L, Dougados M, Goupille P, Cantagrel A, Sibilia J, Meyer O, Sany J, Daures JP, Combe B: Prognostic factors for remission in early rheumatoid arthritis: a multiparameter prospective study. Ann Rheum Dis 2004, 63:675-680.
  • [71]Kavanaugh A, Klareskog L, van der Heijde D, Li J, Freundlich B, Hooper M: Improvements in clinical response between 12 and 24 weeks in patients with rheumatoid arthritis on etanercept therapy with or without methotrexate. Ann Rheum Dis 2008, 67:1444-1447.
  • [72]Thompson PW, Silman AJ, Kirwan JR, Currey HL: Articular indices of joint inflammation in rheumatoid arthritis. Correlation with the acute-phase response. Arthritis Rheum 1987, 30:618-623.
  • [73]Verstappen SM, van Albada-Kuipers GA, Bijlsma JW, Blaauw AA, Schenk Y, Haanen HC, Jacobs JW: A good response to early DMARD treatment of patients with rheumatoid arthritis in the first year predicts remission during follow up. Ann Rheum Dis 2005, 64:38-43.
  • [74]Mottonen T, Hannonen P, Leirisalo-Repo M, Nissila M, Kautiainen H, Korpela M, Laasonen L, Julkunen H, Luukkainen R, Vuori K, Paimela L, Blafield H, Hakala M, Ilva K, Yli-Kerttula U, Puolakka K, Jarvinen P, Hakola M, Piirainen H, Ahonen J, Palvimaki I, Forsberg S, Koota K, Friman C: Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial. FIN-RACo trial group. Lancet 1999, 353:1568-1573.
  • [75]Goetz I, Carter GC, Lucero M, Zarotsky V, Alatorre CI, Cantrell RA, Paczkowski R, Sterling KL: Review of treatment response in rheumatoid arthritis: assessment of heterogeneity. Curr Med Res Opin 2011, 27:697-711.
  • [76]Boers M, Verhoeven AC, Markusse HM, van de Laar MA, Westhovens R, van Denderen JC, van Zeben D, Dijkmans BA, Peeters AJ, Jacobs P, van den Brink HR, Schouten HJ, van der Heijde DM, Boonen A, van der Linden S: Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis. Lancet 1997, 350:309-318.
  • [77]Bakker MF, Jacobs JW, Welsing PM, Verstappen SM, Tekstra J, Ton E, Geurts MA, van der Werf JH, van Albada-Kuipers GA, Jahangier-de Veen ZN, van der Veen MJ, Verhoef CM, Lafeber FP, Bijlsma JW: Low-dose prednisone inclusion in a methotrexate-based, tight control strategy for early rheumatoid arthritis: a randomized trial. Ann Intern Med 2012, 156:329-339.
  • [78]Svensson B, Boonen A, Albertsson K, van der Heijde D, Keller C, Hafstrom I: 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. Arthritis Rheum 2005, 52:3360-3370.
  • [79]Hafstrom I, Albertsson K, Boonen A, van der Heijde D, Landewe R, Svensson B: Remission achieved after 2 years treatment with low-dose prednisolone in addition to disease-modifying anti-rheumatic drugs in early rheumatoid arthritis is associated with reduced joint destruction still present after 4 years: an open 2-year continuation study. Ann Rheum Dis 2009, 68:508-513.
  • [80]Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Menard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, et al.: 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis 2010, 69:1580-1588.
  • [81]Mottonen T, Paimela L, Leirisalo-Repo M, Kautiainen H, Ilonen J, Hannonen P: Only high disease activity and positive rheumatoid factor indicate poor prognosis in patients with early rheumatoid arthritis treated with "sawtooth" strategy. Ann Rheum Dis 1998, 57:533-539.
  • [82]Vittecoq O, Pouplin S, Krzanowska K, Jouen-Beades F, Menard JF, Gayet A, Daragon A, Tron F, Le Loet X: Rheumatoid factor is the strongest predictor of radiological progression of rheumatoid arthritis in a three-year prospective study in community-recruited patients. Rheumatology (Oxford) 2003, 42:939-946.
  • [83]Bukhari M, Lunt M, Harrison BJ, Scott DG, Symmons DP, Silman AJ: Rheumatoid factor is the major predictor of increasing severity of radiographic erosions in rheumatoid arthritis: results from the Norfolk Arthritis Register Study, a large inception cohort. Arthritis Rheum 2002, 46:906-912.
  • [84]da Mota LM, Dos Santos Neto LL, de Carvalho JF, Pereira IA, Burlingame R, Menard HA, Laurindo IM: The presence of anti-citrullinated protein antibodies (ACPA) and rheumatoid factor on patients with rheumatoid arthritis (RA) does not interfere with the chance of clinical remission in a follow-up of 3 years. Rheumatol Int 2012, 32:3807-3812.
  • [85]Morgan C, Lunt M, Brightwell H, Bradburn P, Fallow W, Lay M, Silman A, Bruce IN: Contribution of patient related differences to multidrug resistance in rheumatoid arthritis. Ann Rheum Dis 2003, 62:15-19.
  • [86]Eberhardt K, Fex E: Clinical course and remission rate in patients with early rheumatoid arthritis: relationship to outcome after 5 years. Br J Rheumatol 1998, 37:1324-1329.
  • [87]Forslind K, Hafstrom I, Ahlmen M, Svensson B: Sex: a major predictor of remission in early rheumatoid arthritis? Ann Rheum Dis 2007, 66:46-52.
  • [88]Pease CT, Bhakta BB, Devlin J, Emery P: Does the age of onset of rheumatoid arthritis influence phenotype?: a prospective study of outcome and prognostic factors. Rheumatology (Oxford) 1999, 38:228-234.
  • [89]Bas S, Genevay S, Meyer O, Gabay C: Anti-cyclic citrullinated peptide antibodies, IgM and IgA rheumatoid factors in the diagnosis and prognosis of rheumatoid arthritis. Rheumatology (Oxford) 2003, 42:677-680.
  • [90]van Venrooij WJ, van Beers JJ, Pruijn GJ: Anti-CCP antibody, a marker for the early detection of rheumatoid arthritis. Ann N Y Acad Sci 2008, 1143:268-285.
  • [91]Mutlu N, Bicakcigil M, Tasan DA, Kaya A, Yavuz S, Ozden AI: Comparative performance analysis of 4 different anti-citrullinated protein assays in the diagnosis of rheumatoid arthritis. J Rheumatol 2009, 36:491-500.
  • [92]Schellekens GA, Visser H, de Jong BA, van den Hoogen FH, Hazes JM, Breedveld FC, van Venrooij WJ: The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum 2000, 43:155-163.
  • [93]Balsa A, Del Amo J, Blanco F, Caliz R, Silva L, Sanmarti R, Martinez FG, Tejedor D, Artieda M, Pascual-Salcedo D, Oreiro N, Collado MD, Andreu JL, Graell E, Simon L, Martinez A, Mulero J: Prediction of functional impairment and remission in rheumatoid arthritis patients by biochemical variables and genetic polymorphisms. Rheumatology (Oxford) 2010, 49:458-466.
  • [94]Shidara K, Inoue E, Hoshi D, Sato E, Nakajima A, Momohara S, Taniguchi A, Yamanaka H: Anti-cyclic citrullinated peptide antibody predicts functional disability in patients with rheumatoid arthritis in a large prospective observational cohort in Japan. Rheumatol Int 2012, 32:361-366.
  • [95]Ronnelid J, Wick MC, Lampa J, Lindblad S, Nordmark B, Klareskog L, van Vollenhoven RF: Longitudinal analysis of citrullinated protein/peptide antibodies (anti-CP) during 5 year follow up in early rheumatoid arthritis: anti-CP status predicts worse disease activity and greater radiological progression. Ann Rheum Dis 2005, 64:1744-1749.
  • [96]del Val del Amo N, Ibanez Bosch R, Fito Manteca C, Gutierrez Polo R, Loza Cortina E: Anti-cyclic citrullinated peptide antibody in rheumatoid arthritis: relation with disease aggressiveness. Clin Exp Rheumatol 2006, 24:281-286.
  • [97]Hetland ML, Stengaard-Pedersen K, Junker P, Ostergaard M, Ejbjerg BJ, Jacobsen S, Lottenburger T, Hansen I, Tarp U, Andersen LS, Svendsen A, Pedersen JK, Lauridsen UB, Ellingsen T, Lindegaard H, Podenphant J, Vestergaard A, Jurik AG, Horslev-Petersen K: Radiographic progression and remission rates in early rheumatoid arthritis - MRI bone oedema and anti-CCP predicted radiographic progression in the 5-year extension of the double-blind randomised CIMESTRA trial. Ann Rheum Dis 2010, 69:1789-1795.
  • [98]Syversen SW, Goll GL, van der Heijde D, Landewe R, Lie BA, Odegard S, Uhlig T, Gaarder PI, Kvien TK: Prediction of radiographic progression in rheumatoid arthritis and the role of antibodies against mutated citrullinated vimentin: results from a 10-year prospective study. Ann Rheum Dis 2010, 69:345-351.
  • [99]Nishimura K, Sugiyama D, Kogata Y, Tsuji G, Nakazawa T, Kawano S, Saigo K, Morinobu A, Koshiba M, Kuntz KM, Kamae I, Kumagai S: Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis. Ann Intern Med 2007, 146:797-808.
  • [100]Kroot EJ, de Jong BA, van Leeuwen MA, Swinkels H, van den Hoogen FH, van't Hof M, van de Putte LB, van Rijswijk MH, van Venrooij WJ, van Riel PL: The prognostic value of anti-cyclic citrullinated peptide antibody in patients with recent-onset rheumatoid arthritis. Arthritis Rheum 2000, 43:1831-1835.
  • [101]Meyer O, Labarre C, Dougados M, Goupille P, Cantagrel A, Dubois A, Nicaise-Roland P, Sibilia J, Combe B: Anticitrullinated protein/peptide antibody assays in early rheumatoid arthritis for predicting five year radiographic damage. Ann Rheum Dis 2003, 62:120-126.
  • [102]Forslind K, Ahlmen M, Eberhardt K, Hafstrom I, Svensson B: Prediction of radiological outcome in early rheumatoid arthritis in clinical practice: role of antibodies to citrullinated peptides (anti-CCP). Ann Rheum Dis 2004, 63:1090-1095.
  • [103]Sanmarti R, Gomez-Centeno A, Ercilla G, Larrosa M, Vinas O, Vazquez I, Gomez-Puerta JA, Gratacos J, Salvador G, Canete JD: Prognostic factors of radiographic progression in early rheumatoid arthritis: a two year prospective study after a structured therapeutic strategy using DMARDs and very low doses of glucocorticoids. Clin Rheumatol 2007, 26:1111-1118.
  • [104]van der Helm-van Mil AH, Verpoort KN, Breedveld FC, Toes RE, Huizinga TW: Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis. Arthritis Res Ther 2005, 7:R949-958. BioMed Central Full Text
  • [105]Berglin E, Johansson T, Sundin U, Jidell E, Wadell G, Hallmans G, Rantapaa-Dahlqvist S: Radiological outcome in rheumatoid arthritis is predicted by presence of antibodies against cyclic citrullinated peptide before and at disease onset, and by IgA-RF at disease onset. Ann Rheum Dis 2006, 65:453-458.
  • [106]van der Helm-van Mil AH, le Cessie S, van Dongen H, Breedveld FC, Toes RE, Huizinga TW: A prediction rule for disease outcome in patients with recent-onset undifferentiated arthritis: how to guide individual treatment decisions. Arthritis Rheum 2007, 56:433-440.
  • [107]Cao Y, Bonner A, Barra LJ, Thorne JC, Haraoui B, Boire B, Hitchon CA, Le Riche NGH, Thompson AE, Keystone E, Bykerk V, Pope JE, CATCH Investigators: Response to second-line DMARDs and TNFi in seropositive and seronegative patients in early and late rheumatoid arthritis are not the same: results from the CATCH cohort and a large, established rheumatoid arthritis database [abstract]. Arthritis Rheum 2011, 63(Suppl 10):2202.
  • [108]Verschueren P, Esselens G, Westhovens R: Predictors of remission, normalized physical function, and changes in the working situation during follow-up of patients with early rheumatoid arthritis: an observational study. Scand J Rheumatol 2009, 38:166-172.
  • [109]Boire G, Cossette P, de Brum-Fernandes AJ, Liang P, Niyonsenga T, Zhou ZJ, Carrier N, Daniel C, Menard HA: Anti-Sa antibodies and antibodies against cyclic citrullinated peptide are not equivalent as predictors of severe outcomes in patients with recent-onset polyarthritis. Arthritis Res Ther 2005, 7:R592-603. BioMed Central Full Text
  • [110]van den Broek M, Dirven L, Klarenbeek NB, Molenaar TH, Han KH, Kerstens PJ, Huizinga TW, Dijkmans BA, Allaart CF: The association of treatment response and joint damage with ACPA-status in recent-onset RA: a subanalysis of the 8-year follow-up of the BeSt study. Ann Rheum Dis 2012, 71:245-248.
  • [111]van der Woude D, Young A, Jayakumar K, Mertens BJ, Toes RE, van der Heijde D, Huizinga TW, van der Helm-van Mil AH: Prevalence of and predictive factors for sustained disease-modifying antirheumatic drug-free remission in rheumatoid arthritis: results from two large early arthritis cohorts. Arthritis Rheum 2009, 60:2262-2271.
  • [112]Mori S, Hirose J, Yonemura K: Contribution of HLA-DRB1*04 alleles and anti-cyclic citrullinated antibodies to development of resistance to disease-modifying antirheumatic drugs in early rheumatoid arthritis. Clin Rheumatol 2010, 29:1357-1366.
  • [113]Verstappen SM, Lunt M, Bunn DK, Scott DG, Symmons DP: In patients with early inflammatory polyarthritis, ACPA positivity, younger age and inefficacy of the first non-biological DMARD are predictors for receiving biological therapy: results from the Norfolk Arthritis Register. Ann Rheum Dis 2011, 70:1428-1432.
  • [114]Kastbom A, Strandberg G, Lindroos A, Skogh T: Anti-CCP antibody test predicts the disease course during 3 years in early rheumatoid arthritis (the Swedish TIRA project). Ann Rheum Dis 2004, 63:1085-1089.
  • [115]van Dongen H, van Aken J, Lard LR, Visser K, Ronday HK, Hulsmans HM, Speyer I, Westedt ML, Peeters AJ, Allaart CF, Toes RE, Breedveld FC, Huizinga TW: Efficacy of methotrexate treatment in patients with probable rheumatoid arthritis: a double-blind, randomized, placebo-controlled trial. Arthritis Rheum 2007, 56:1424-1432.
  • [116]Visser K, Verpoort KN, van Dongen H, van der Kooij SM, Allaart CF, Toes RE, Huizinga TW, van der Helm-van Mil AH: Pretreatment serum levels of anti-cyclic citrullinated peptide antibodies are associated with the response to methotrexate in recent-onset arthritis. Ann Rheum Dis 2008, 67:1194-1195.
  • [117]Bang H, Egerer K, Gauliard A, Luthke K, Rudolph PE, Fredenhagen G, Berg W, Feist E, Burmester GR: Mutation and citrullination modifies vimentin to a novel autoantigen for rheumatoid arthritis. Arthritis Rheum 2007, 56:2503-2511.
  • [118]Puszczewicz M, Iwaszkiewicz C: Role of anti-citrullinated protein antibodies in diagnosis and prognosis of rheumatoid arthritis. Arch Med Sci 2011, 7:189-194.
  • [119]Dejaco C, Klotz W, Larcher H, Duftner C, Schirmer M, Herold M: Diagnostic value of antibodies against a modified citrullinated vimentin in rheumatoid arthritis. Arthritis Res Ther 2006, 8:R119. BioMed Central Full Text
  • [120]Mathsson L, Mullazehi M, Wick MC, Sjoberg O, van Vollenhoven R, Klareskog L, Ronnelid J: Antibodies against citrullinated vimentin in rheumatoid arthritis: higher sensitivity and extended prognostic value concerning future radiographic progression as compared with antibodies against cyclic citrullinated peptides. Arthritis Rheum 2008, 58:36-45.
  • [121]Poulsom H, Charles PJ: Antibodies to citrullinated vimentin are a specific and sensitive marker for the diagnosis of rheumatoid arthritis. Clin Rev Allergy Immunol 2008, 34:4-10.
  • [122]Damjanovska L, Thabet MM, Levarth EW, Stoeken-Rijsbergen G, van der Voort EI, Toes RE, Huizinga TW, van der Helm-van Mil AH: Diagnostic value of anti-MCV antibodies in differentiating early inflammatory arthritis. Ann Rheum Dis 2010, 69:730-732.
  • [123]Innala L, Kokkonen H, Eriksson C, Jidell E, Berglin E, Dahlqvst SR: Antibodies against mutated citrullinated vimentin are a better predictor of disease activity at 24 months in early rheumatoid arthritis than antibodies against cyclic citrullinated peptides. J Rheumatol 2008, 35:1002-1008.
  • [124]Wagner E, Skoumal M, Bayer PM, Klaushofer K: Antibody against mutated citrullinated vimentin: a new sensitive marker in the diagnosis of rheumatoid arthritis. Rheumatol Int 2009, 29:1315-1321.
  • [125]Luime JJ, Colin EM, Hazes JM, Lubberts E: Does anti-mutated citrullinated vimentin have additional value as a serological marker in the diagnostic and prognostic investigation of patients with rheumatoid arthritis? A systematic review. Ann Rheum Dis 2010, 69:337-344.
  • [126]Sizova L: Diagnostic value of antibodies to modified citrullinated vimentin in early rheumatoid arthritis. Hum Immunol 2012, 73:389-392.
  • [127]Raza K, Mathsson L, Buckley CD, Filer A, Ronnelid J: Anti-modified citrullinated vimentin (MCV) antibodies in patients with very early synovitis. Ann Rheum Dis 2010, 69:627-628.
  • [128]Ursum J, Nielen MM, van Schaardenburg D, van der Horst AR, van de Stadt RJ, Dijkmans BA, Hamann D: Antibodies to mutated citrullinated vimentin and disease activity score in early arthritis: a cohort study. Arthritis Res Ther 2008, 10:R12. BioMed Central Full Text
  • [129]Raj DS: Role of interleukin-6 in the anemia of chronic disease. Semin Arthritis Rheum 2009, 38:382-388.
  • [130]Furst DE, Chang H, Greenberg JD, Ranganath VK, Reed G, Ozturk ZE, Kremer JM: Prevalence of low hemoglobin levels and associations with other disease parameters in rheumatoid arthritis patients: evidence from the CORRONA registry. Clin Exp Rheumatol 2009, 27:560-566.
  • [131]McInnes IB, Schett G: The pathogenesis of rheumatoid arthritis. N Engl J Med 2011, 365:2205-2219.
  • [132]Gerards AH, de Lathouder S, de Groot ER, Dijkmans BA, Aarden LA: Inhibition of cytokine production by methotrexate. Studies in healthy volunteers and patients with rheumatoid arthritis. Rheumatology (Oxford) 2003, 42:1189-1196.
  • [133]Aggarwal A, Misra R: Methotrexate inhibits interleukin-6 production in patients with juvenile rheumatoid arthritis. Rheumatol Int 2003, 23:134-137.
  • [134]Seitz M, Zwicker M, Villiger PM: Pretreatment cytokine profiles of peripheral blood mononuclear cells and serum from patients with rheumatoid arthritis in different american college of rheumatology response groups to methotrexate. J Rheumatol 2003, 30:28-35.
  • [135]Seitz M, Zwicker M, Wider B: Enhanced in vitro induced production of interleukin 10 by peripheral blood mononuclear cells in rheumatoid arthritis is associated with clinical response to methotrexate treatment. J Rheumatol 2001, 28:496-501.
  • [136]Rudwaleit M, Yin Z, Siegert S, Grolms M, Radbruch A, Braun J, Sieper J: Response to methotrexate in early rheumatoid arthritis is associated with a decrease of T cell derived tumour necrosis factor alpha, increase of interleukin 10, and predicted by the initial concentration of interleukin 4. Ann Rheum Dis 2000, 59:311-314.
  • [137]van der Graaff WL, Prins AP, Dijkmans BA, van Lier RA: Prognostic value of Th1/Th2 ratio in rheumatoid arthritis. Lancet 1998, 351:1931.
  • [138]Kuuliala A, Leirisalo-Repo M, Mottonen T, Hannonen P, Nissila M, Kautiainen H, Korpela M, Julkunen H, Hakola M, Repo H: Serum soluble interleukin-2 receptor predicts early remission in patients with recent-onset rheumatoid arthritis treated with a single disease-modifying antirheumatic drug. Clin Exp Rheumatol 2005, 23:243-246.
  • [139]Polisson RP, Dooley MA, Dawson DV, Pisetsky DS: Interleukin-2 receptor levels in the sera of rheumatoid arthritis patients treated with methotrexate. Arthritis Rheum 1994, 37:50-56.
  • [140]Merkel PA, Dooley MA, Dawson DV, Pisetsky DS, Polisson RP: Interleukin-2 receptor levels in sera of patients with rheumatoid arthritis treated with sulfasalazine, parenteral gold, or placebo. J Rheumatol 1996, 23:1856-1861.
  • [141]Gerli R, Bistoni O, Lunardi C, Giacomelli R, Tomassini C, Biagini P, Pitzalis C: Soluble CD30 in early rheumatoid arthritis as a predictor of good response to second-line therapy. Rheumatology (Oxford) 1999, 38:1282-1284.
  • [142]Savolainen E, Matinlauri I, Kautiainen H, Luosujarvi R, Kaipiainen-Seppanen O: Serum soluble CD30 in early arthritis: a sign of inflammation but not a predictor of outcome. Clin Exp Rheumatol 2008, 26:922-925.
  • [143]Haroon N, Srivastava R, Misra R, Aggarwal A: A novel predictor of clinical response to methotrexate in patients with rheumatoid arthritis: a pilot study of in vitro T cell cytokine suppression. J Rheumatol 2008, 35:975-978.
  • [144]Ercan A, Cui J, Hazen MM, Batliwalla F, Royle L, Rudd PM, Coblyn JS, Shadick N, Weinblatt ME, Gregersen P, Lee DM, Nigrovic PA: Hypogalactosylation of serum N-glycans fails to predict clinical response to methotrexate and TNF inhibition in rheumatoid arthritis. Arthritis Res Ther 2012, 14:R43. BioMed Central Full Text
  • [145]Posthumus MD, Limburg PC, Westra J, van Leeuwen MA, van Rijswijk MH: Serum matrix metalloproteinase 3 levels during treatment with sulfasalazine or combination of methotrexate and sulfasalazine in patients with early rheumatoid arthritis. J Rheumatol 2002, 29:883-889.
  • [146]Ribbens C, Andre B, Jaspar JM, Kaye O, Kaiser MJ, De Groote D, Malaise MG: Matrix metalloproteinase-3 serum levels are correlated with disease activity and predict clinical response in rheumatoid arthritis. J Rheumatol 2000, 27:888-893.
  • [147]Baggott JE, Morgan SL: Methotrexate catabolism to 7-hydroxymethotrexate in rheumatoid arthritis alters drug efficacy and retention and is reduced by folic acid supplementation. Arthritis Rheum 2009, 60:2257-2261.
  • [148]Baggott JE, Vaughn WH, Hudson BB: Inhibition of 5-aminoimidazole-4-carboxamide ribotide transformylase, adenosine deaminase and 5'-adenylate deaminase by polyglutamates of methotrexate and oxidized folates and by 5-aminoimidazole-4-carboxamide riboside and ribotide. Biochem J 1986, 236:193-200.
  • [149]Dervieux T, Furst D, Lein DO, Capps R, Smith K, Caldwell J, Kremer J: Pharmacogenetic and metabolite measurements are associated with clinical status in patients with rheumatoid arthritis treated with methotrexate: results of a multicentred cross sectional observational study. Ann Rheum Dis 2005, 64:1180-1185.
  • [150]Dervieux T, Greenstein N, Kremer J: Pharmacogenomic and metabolic biomarkers in the folate pathway and their association with methotrexate effects during dosage escalation in rheumatoid arthritis. Arthritis Rheum 2006, 54:3095-3103.
  • [151]Hobl EL, Jilma B, Erlacher L, Duhm B, Mustak M, Broll H, Hogger P, Rizovski B, Mader RM: A short-chain methotrexate polyglutamate as outcome parameter in rheumatoid arthritis patients receiving methotrexate. Clin Exp Rheumatol 2012, 30:156-163.
  • [152]Kato T, Hamada A, Mori S, Saito H: Genetic polymorphisms in metabolic and cellular transport pathway of methotrexate impact clinical outcome of methotrexate monotherapy in Japanese patients with rheumatoid arthritis. Drug Metab Pharmacokinet 2012, 27:192-199.
  • [153]Pettit AR, Weedon H, Ahern M, Zehntner S, Frazer IH, Slavotinek J, Au V, Smith MD, Thomas R: Association of clinical, radiological and synovial immunopathological responses to anti-rheumatic treatment in rheumatoid arthritis. Rheumatology (Oxford) 2001, 40:1243-1255.
  • [154]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.
  • [155]Winchester R, Dwyer E, Rose S: The genetic basis of rheumatoid arthritis. The shared epitope hypothesis. Rheum Dis Clin North Am 1992, 18:761-783.
  • [156]Moxley G, Cohen HJ: Genetic studies, clinical heterogeneity, and disease outcome studies in rheumatoid arthritis. Rheum Dis Clin North Am 2002, 28:39-58.
  • [157]Gorman JD, Criswell LA: The shared epitope and severity of rheumatoid arthritis. Rheum Dis Clin North Am 2002, 28:59-78.
  • [158]Weyand CM, Hicok KC, Conn DL, Goronzy JJ: The influence of HLA-DRB1 genes on disease severity in rheumatoid arthritis. Ann Intern Med 1992, 117:801-806.
  • [159]Goronzy JJ, Matteson EL, Fulbright JW, Warrington KJ, Chang-Miller A, Hunder GG, Mason TG, Nelson AM, Valente RM, Crowson CS, Erlich HA, Reynolds RL, Swee RG, O'Fallon WM, Weyand CM: Prognostic markers of radiographic progression in early rheumatoid arthritis. Arthritis Rheum 2004, 50:43-54.
  • [160]Ferraccioli GF, Gremese E, Tomietto P, Favret G, Damato R, Di Poi E: Analysis of improvements, full responses, remission and toxicity in rheumatoid patients treated with step-up combination therapy (methotrexate, cyclosporin A, sulphasalazine) or monotherapy for three years. Rheumatology (Oxford) 2002, 41:892-898.
  • [161]Gonzalez-Gay MA, Hajeer AH, Garcia-Porrua C, Dababneh A, Thomson W, Ollier WE, Mattey DL: Patients chosen for treatment with cyclosporine because of severe rheumatoid arthritis are more likely to carry HLA-DRB1 shared epitope alleles, and have earlier disease onset. J Rheumatol 2002, 29:271-275.
  • [162]Ali AA, Moatter T, Baig JA, Iqbal A, Hussain A, Iqbal MP: Polymorphism of HLA-DR and HLA-DQ in rheumatoid arthritis patients and clinical response to methotrexate--a hospital-based study. J Pak Med Assoc 2006, 56:452-456.
  • [163]Molenaar ET, Voskuyl AE, van der Horst-Bruinsma IE, Schreuder GM, Zanelli E, Dijkmans BA: Influence of HLA polymorphism on persistent remission in rheumatoid arthritis. Ann Rheum Dis 2002, 61:351-353.
  • [164]Saruhan-Direskeneli G, Inanc M, Fresko I, Akkoc N, Dalkilic E, Erken E, Karaaslan Y, Kinikli G, Oksel F, Pay S, Yucel E, Yentur SP, Duymaz-Tozkir J, Yilmaz V, Inanc N, Yazici H, Konice M, Direskeneli H: The role of HLA-DRB1 shared epitope alleles in predicting short-term response to leflunomide in rheumatoid arthritis. Rheumatology (Oxford) 2007, 46:1842-1844.
  • [165]Dervieux T, Lein DO, Park G, Barham R, Smith K, Walsh M: Single nucleotide polymorphisms (SNPs) in the folate/purine synthesis pathway predict methotrexate's effects in rhematoid arthritis. Arthritis Rheum 2003, 48(Suppl 9):S438.
  • [166]James HM, Gillis D, Hissaria P, Lester S, Somogyi AA, Cleland LG, Proudman SM: Common polymorphisms in the folate pathway predict efficacy of combination regimens containing methotrexate and sulfasalazine in early rheumatoid arthritis. J Rheumatol 2008, 35:562-571.
  • [167]Drozdzik M, Rudas T, Pawlik A, Gornik W, Kurzawski M, Herczynska M: Reduced folate carrier-1 80G>A polymorphism affects methotrexate treatment outcome in rheumatoid arthritis. Pharmacogenomics J 2007, 7:404-407.
  • [168]Dervieux T, Kremer J, Lein DO, Capps R, Barham R, Meyer G, Smith K, Caldwell J, Furst DE: Contribution of common polymorphisms in reduced folate carrier and gamma-glutamylhydrolase to methotrexate polyglutamate levels in patients with rheumatoid arthritis. Pharmacogenetics 2004, 14:733-739.
  • [169]Laverdiere C, Chiasson S, Costea I, Moghrabi A, Krajinovic M: Polymorphism G80A in the reduced folate carrier gene and its relationship to methotrexate plasma levels and outcome of childhood acute lymphoblastic leukemia. Blood 2002, 100:3832-3834.
  • [170]Baslund B, Gregers J, Nielsen CH: Reduced folate carrier polymorphism determines methotrexate uptake by B cells and CD4+ T cells. Rheumatology (Oxford) 2008, 47:451-453.
  • [171]Wessels JA, de Vries-Bouwstra JK, Heijmans BT, Slagboom PE, Goekoop-Ruiterman YP, Allaart CF, Kerstens PJ, van Zeben D, Breedveld FC, Dijkmans BA, Huizinga TW, Guchelaar HJ: Efficacy and toxicity of methotrexate in early rheumatoid arthritis are associated with single-nucleotide polymorphisms in genes coding for folate pathway enzymes. Arthritis Rheum 2006, 54:1087-1095.
  • [172]Takatori R, Takahashi KA, Tokunaga D, Hojo T, Fujioka M, Asano T, Hirata T, Kawahito Y, Satomi Y, Nishino H, Tanaka T, Hirota Y, Kubo T: ABCB1 C3435T polymorphism influences methotrexate sensitivity in rheumatoid arthritis patients. Clin Exp Rheumatol 2006, 24:546-554.
  • [173]Owen SA, Hider SL, Martin P, Bruce IN, Barton A, Thomson W: Genetic polymorphisms in key methotrexate pathway genes are associated with response to treatment in rheumatoid arthritis patients. Pharmacogenomics J 2012. doi: 10.1038/tpj.2012.7
  • [174]Stamp LK, Roberts RL: Effect of genetic polymorphisms in the folate pathway on methotrexate therapy in rheumatic diseases. Pharmacogenomics 2011, 12:1449-1463.
  • [175]van der Heijden JW, Dijkmans BA, Scheper RJ, Jansen G: Drug Insight: resistance to methotrexate and other disease-modifying antirheumatic drugs--from bench to bedside. Nat Clin Pract Rheumatol 2007, 3:26-34.
  • [176]Ranganathan P: An update on methotrexate pharmacogenetics in rheumatoid arthritis. Pharmacogenomics 2008, 9:439-451.
  • [177]Pawlik A, Wrzesniewska J, Fiedorowicz-Fabrycy I, Gawronska-Szklarz B: The MDR1 3435 polymorphism in patients with rheumatoid arthritis. Int J Clin Pharmacol Ther 2004, 42:496-503.
  • [178]Drozdzik M, Rudas T, Pawlik A, Kurzawski M, Czerny B, Gornik W, Herczynska M: The effect of 3435C>T MDR1 gene polymorphism on rheumatoid arthritis treatment with disease-modifying antirheumatic drugs. Eur J Clin Pharmacol 2006, 62:933-937.
  • [179]Bohanec Grabar P, Logar D, Lestan B, Dolzan V: Genetic determinants of methotrexate toxicity in rheumatoid arthritis patients: a study of polymorphisms affecting methotrexate transport and folate metabolism. Eur J Clin Pharmacol 2008, 64:1057-1068.
  • [180]Kooloos WM, Wessels JA, van der Straaten T, Allaart CF, Huizinga TW, Guchelaar HJ: Functional polymorphisms and methotrexate treatment outcome in recent-onset rheumatoid arthritis. Pharmacogenomics 2010, 11:163-175.
  • [181]Ranganathan P, Culverhouse R, Marsh S, Ahluwalia R, Shannon WD, Eisen S, McLeod HL: Single nucleotide polymorphism profiling across the methotrexate pathway in normal subjects and patients with rheumatoid arthritis. Pharmacogenomics 2004, 5:559-569.
  • [182]Warren RB, Smith RL, Campalani E, Eyre S, Smith CH, Barker JN, Worthington J, Griffiths CE: Genetic variation in efflux transporters influences outcome to methotrexate therapy in patients with psoriasis. J Invest Dermatol 2008, 128:1925-1929.
  • [183]Cheng Q, Wu B, Kager L, Panetta JC, Zheng J, Pui CH, Relling MV, Evans WE: A substrate specific functional polymorphism of human gamma-glutamyl hydrolase alters catalytic activity and methotrexate polyglutamate accumulation in acute lymphoblastic leukaemia cells. Pharmacogenetics 2004, 14:557-567.
  • [184]van der Straaten RJ, Wessels JA, de Vries-Bouwstra JK, Goekoop-Ruiterman YP, Allaart CF, Bogaartz J, Tiller M, Huizinga TW, Guchelaar HJ: Exploratory analysis of four polymorphisms in human GGH and FPGS genes and their effect in methotrexate-treated rheumatoid arthritis patients. Pharmacogenomics 2007, 8:141-150.
  • [185]Sharma S, Das M, Kumar A, Marwaha V, Shankar S, Singh P, Raghu P, Aneja R, Grover R, Arya V, Dhir V, Gupta R, Kumar U, Juyal RC, Thelma BK: Purine biosynthetic pathway genes and methotrexate response in rheumatoid arthritis patients among north Indians. Pharmacogenet Genomics 2009, 19:823-828.
  • [186]Horie N, Aiba H, Oguro K, Hojo H, Takeishi K: Functional analysis and DNA polymorphism of the tandemly repeated sequences in the 5'-terminal regulatory region of the human gene for thymidylate synthase. Cell Struct Funct 1995, 20:191-197.
  • [187]Dervieux T, Furst D, Lein DO, Capps R, Smith K, Walsh M, Kremer J: Polyglutamation of methotrexate with common polymorphisms in reduced folate carrier, aminoimidazole carboxamide ribonucleotide transformylase, and thymidylate synthase are associated with methotrexate effects in rheumatoid arthritis. Arthritis Rheum 2004, 50:2766-2774.
  • [188]Kumagai K, Hiyama K, Oyama T, Maeda H, Kohno N: Polymorphisms in the thymidylate synthase and methylenetetrahydrofolate reductase genes and sensitivity to the low-dose methotrexate therapy in patients with rheumatoid arthritis. Int J Mol Med 2003, 11:593-600.
  • [189]Inoue S, Hashiguchi M, Takagi K, Kawai S, Mochizuki M: Preliminary study to identify the predictive factors for the response to methotrexate therapy in patients with rheumatoid arthritis. Yakugaku Zasshi 2009, 129:843-849.
  • [190]Ulrich CM, Bigler J, Velicer CM, Greene EA, Farin FM, Potter JD: Searching expressed sequence tag databases: discovery and confirmation of a common polymorphism in the thymidylate synthase gene. Cancer Epidemiol Biomarkers Prev 2000, 9:1381-1385.
  • [191]Mandola MV, Stoehlmacher J, Zhang W, Groshen S, Yu MC, Iqbal S, Lenz HJ, Ladner RD: A 6 bp polymorphism in the thymidylate synthase gene causes message instability and is associated with decreased intratumoral TS mRNA levels. Pharmacogenetics 2004, 14:319-327.
  • [192]Banerjee D, Mayer-Kuckuk P, Capiaux G, Budak-Alpdogan T, Gorlick R, Bertino JR: Novel aspects of resistance to drugs targeted to dihydrofolate reductase and thymidylate synthase. Biochim Biophys Acta 2002, 1587:164-173.
  • [193]Goto Y, Yue L, Yokoi A, Nishimura R, Uehara T, Koizumi S, Saikawa Y: A novel single-nucleotide polymorphism in the 3'-untranslated region of the human dihydrofolate reductase gene with enhanced expression. Clin Cancer Res 2001, 7:1952-1956.
  • [194]Milic V, Jekic B, Lukovic L, Bunjevacki V, Milasin J, Novakovic I, Damnjanovic T, Popovic B, Maksimovic N, Damjanov N, Radunovic G, Pejnovic N, Krajinovic M: Association of dihydrofolate reductase (DHFR) -317AA genotype with poor response to methotrexate in patients with rheumatoid arthritis. Clin Exp Rheumatol 2012, 30:178-183.
  • [195]Lee YC, Cui J, Costenbader KH, Shadick NA, Weinblatt ME, Karlson EW: Investigation of candidate polymorphisms and disease activity in rheumatoid arthritis patients on methotrexate. Rheumatology (Oxford) 2009, 48:613-617.
  • [196]Wessels JA, Kooloos WM, De Jonge R, De Vries-Bouwstra JK, Allaart CF, Linssen A, Collee G, De Sonnaville P, Lindemans J, Huizinga TW, Guchelaar HJ: Relationship between genetic variants in the adenosine pathway and outcome of methotrexate treatment in patients with recent-onset rheumatoid arthritis. Arthritis Rheum 2006, 54:2830-2839.
  • [197]Hinks A, Moncrieffe H, Martin P, Ursu S, Lal S, Kassoumeri L, Weiler T, Glass DN, Thompson SD, Wedderburn LR, Thomson W: Association of the 5-aminoimidazole-4-carboxamide ribonucleotide transformylase gene with response to methotrexate in juvenile idiopathic arthritis. Ann Rheum Dis 2011, 70:1395-1400.
  • [198]van Ede AE, Laan RF, Blom HJ, Huizinga TW, Haagsma CJ, Giesendorf BA, de Boo TM, van de Putte LB: The C677T mutation in the methylenetetrahydrofolate reductase gene: a genetic risk factor for methotrexate-related elevation of liver enzymes in rheumatoid arthritis patients. Arthritis Rheum 2001, 44:2525-2530.
  • [199]Kang SS, Zhou J, Wong PW, Kowalisyn J, Strokosch G: Intermediate homocysteinemia: a thermolabile variant of methylenetetrahydrofolate reductase. Am J Hum Genet 1988, 43:414-421.
  • [200]Ulrich CM, Robien K, Sparks R: Pharmacogenetics and folate metabolism -- a promising direction. Pharmacogenomics 2002, 3:299-313.
  • [201]Weisberg I, Tran P, Christensen B, Sibani S, Rozen R: A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab 1998, 64:169-172.
  • [202]Hider SL, Bruce IN, Thomson W: The pharmacogenetics of methotrexate. Rheumatology (Oxford) 2007, 46:1520-1524.
  • [203]van der Put NM, Gabreels F, Stevens EM, Smeitink JA, Trijbels FJ, Eskes TK, van den Heuvel LP, Blom HJ: A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? Am J Hum Genet 1998, 62:1044-1051.
  • [204]Wesoly J, Wessels JA, Guchelaar HJ, Huizinga TW: Genetic markers of treatment response in rheumatoid arthritis. Curr Rheumatol Rep 2006, 8:369-377.
  • [205]Kurzawski M, Pawlik A, Safranow K, Herczynska M, Drozdzik M: 677C>T and 1298A>C MTHFR polymorphisms affect methotrexate treatment outcome in rheumatoid arthritis. Pharmacogenomics 2007, 8:1551-1559.
  • [206]Aggarwal P, Naik S, Mishra KP, Aggarwal A, Misra R: Correlation between methotrexate efficacy & toxicity with C677T polymorphism of the methylenetetrahydrofolate gene in rheumatoid arthritis patients on folate supplementation. Indian J Med Res 2006, 124:521-526.
  • [207]van Ede AE, Laan RF, Rood MJ, Huizinga TW, van de Laar MA, van Denderen CJ, Westgeest TA, Romme TC, de Rooij DJ, Jacobs MJ, de Boo TM, van der Wilt GJ, Severens JL, Hartman M, Krabbe PF, Dijkmans BA, Breedveld FC, van de Putte LB: Effect of folic or folinic acid supplementation on the toxicity and efficacy of methotrexate in rheumatoid arthritis: a forty-eight week, multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum 2001, 44:1515-1524.
  • [208]Taniguchi A, Urano W, Tanaka E, Furihata S, Kamitsuji S, Inoue E, Yamanaka M, Yamanaka H, Kamatani N: Validation of the associations between single nucleotide polymorphisms or haplotypes and responses to disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: a proposal for prospective pharmacogenomic study in clinical practice. Pharmacogenet Genomics 2007, 17:383-390.
  • [209]Urano W, Taniguchi A, Yamanaka H, Tanaka E, Nakajima H, Matsuda Y, Akama H, Kitamura Y, Kamatani N: Polymorphisms in the methylenetetrahydrofolate reductase gene were associated with both the efficacy and the toxicity of methotrexate used for the treatment of rheumatoid arthritis, as evidenced by single locus and haplotype analyses. Pharmacogenetics 2002, 12:183-190.
  • [210]Berkun Y, Levartovsky D, Rubinow A, Orbach H, Aamar S, Grenader T, Abou Atta I, Mevorach D, Friedman G, Ben-Yehuda A: Methotrexate related adverse effects in patients with rheumatoid arthritis are associated with the A1298C polymorphism of the MTHFR gene. Ann Rheum Dis 2004, 63:1227-1231.
  • [211]Hughes LB, Beasley TM, Patel H, Tiwari HK, Morgan SL, Baggott JE, Saag KG, McNicholl J, Moreland LW, Alarcon GS, Bridges SL Jr: Racial or ethnic differences in allele frequencies of single-nucleotide polymorphisms in the methylenetetrahydrofolate reductase gene and their influence on response to methotrexate in rheumatoid arthritis. Ann Rheum Dis 2006, 65:1213-1218.
  • [212]Ghodke Y, Chopra A, Joshi K, Patwardhan B: Are thymidylate synthase and methylene tetrahydrofolate reductase genes linked with methotrexate response (efficacy, toxicity) in Indian (Asian) rheumatoid arthritis patients? Clin Rheumatol 2008, 27:787-789.
  • [213]Owen SA, Lunt M, Bowes J, Hider SL, Bruce IN, Thomson W, Barton A: MTHFR gene polymorphisms and outcome of methotrexate treatment in patients with rheumatoid arthritis: analysis of key polymorphisms and meta-analysis of C677T and A1298C polymorphisms. Pharmacogenomics J 2011. doi: 10.1038/tpj.2011.42
  • [214]Taraborelli M, Andreoli L, Archetti S, Ferrari M, Cattaneo R, Tincani A: Methylenetetrahydrofolate reductase polymorphisms and methotrexate: no association with response to therapy nor with drug-related adverse events in an Italian population of rheumatic patients. Clin Exp Rheumatol 2009, 27:499-502.
  • [215]Hayashi H, Fujimaki C, Daimon T, Tsuboi S, Matsuyama T, Itoh K: Genetic polymorphisms in folate pathway enzymes as a possible marker for predicting the outcome of methotrexate therapy in Japanese patients with rheumatoid arthritis. J Clin Pharm Ther 2009, 34:355-361.
  • [216]Lee YH, Song GG: Associations between the C677T and A1298C polymorphisms of MTHFR and the efficacy and toxicity of methotrexate in rheumatoid arthritis: a meta-analysis. Clin Drug Investig 2010, 30:101-108.
  • [217]Sharma S, Das M, Kumar A, Marwaha V, Shankar S, Aneja R, Grover R, Arya V, Dhir V, Gupta R, Kumar U, Juyal RC, Thelma BK: Interaction of genes from influx-metabolism-efflux pathway and their influence on methotrexate efficacy in rheumatoid arthritis patients among Indians. Pharmacogenet Genomics 2008, 18:1041-1049.
  • [218]Dervieux T, Wessels JA, van der Straaten T, Penrod N, Moore JH, Guchelaar HJ, Kremer JM: Gene-gene interactions in folate and adenosine biosynthesis pathways affect methotrexate efficacy and tolerability in rheumatoid arthritis. Pharmacogenet Genomics 2009, 19:935-944.
  • [219]Dervieux T, Wessels JA, Kremer JM, Padyukov L, Seddighzadeh M, Saevarsdottir S, van Vollenhoven RF, Klareskog L, Huizinga TW, Guchelaar HJ: Patterns of interaction between genetic and nongenetic attributes and methotrexate efficacy in rheumatoid arthritis. Pharmacogenet Genomics 2012, 22:1-9.
  • [220]Hider SL, Bruce IN, Silman AJ, Symmons DP: Defining response to disease modifying antirheumatic drugs in patients with rheumatoid arthritis. J Rheumatol 2005, 32:6-10.
  • [221]Galivan J: Evidence for the cytotoxic activity of polyglutamate derivatives of methotrexate. Mol Pharmacol 1980, 17:105-110.
  • [222]Hooijberg JH, Broxterman HJ, Kool M, Assaraf YG, Peters GJ, Noordhuis P, Scheper RJ, Borst P, Pinedo HM, Jansen G: Antifolate resistance mediated by the multidrug resistance proteins MRP1 and MRP2. Cancer Res 1999, 59:2532-2535.
  • [223]Zeng H, Chen ZS, Belinsky MG, Rea PA, Kruh GD: Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport. Cancer Res 2001, 61:7225-7232.
  • [224]Kool M, van der Linden M, de Haas M, Scheffer GL, de Vree JM, Smith AJ, Jansen G, Peters GJ, Ponne N, Scheper RJ, Elferink RP, Baas F, Borst P: MRP3, an organic anion transporter able to transport anti-cancer drugs. Proc Natl Acad Sci USA 1999, 96:6914-6919.
  • [225]White JC, Goldman ID: Mechanism of action of methotrexate. IV. Free intracellular methotrexate required to suppress dihydrofolate reduction to tetrahydrofolate by Ehrlich ascites tumor cells in vitro. Mol Pharmacol 1976, 12:711-719.
  • [226]Allegra CJ, Chabner BA, Drake JC, Lutz R, Rodbard D, Jolivet J: Enhanced inhibition of thymidylate synthase by methotrexate polyglutamates. J Biol Chem 1985, 260:9720-9726.
  • [227]Szeto DW, Cheng YC, Rosowsky A, Yu CS, Modest EJ, Piper JR, Temple C Jr, Elliott RD, Rose JD, Montgomery JA: Human thymidylate synthetase--III. Effects of methotrexate and folate analogs. Biochem Pharmacol 1979, 28:2633-2637.
  • [228]Allegra CJ, Drake JC, Jolivet J, Chabner BA: Inhibition of phosphoribosylaminoimidazolecarboxamide transformylase by methotrexate and dihydrofolic acid polyglutamates. Proc Natl Acad Sci USA 1985, 82:4881-4885.
  • [229]Chan ES, Cronstein BN: Molecular action of methotrexate in inflammatory diseases. Arthritis Res 2002, 4:266-273. BioMed Central Full Text
  • [230]Cronstein BN, Naime D, Ostad E: The antiinflammatory mechanism of methotrexate. Increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vivo model of inflammation. J Clin Invest 1993, 92:2675-2682.
  • [231]Alarcon GS, Kremer JM, Macaluso M, Weinblatt ME, Cannon GW, Palmer WR, St Clair EW, Sundy JS, Alexander RW, Smith GJ, Axiotis CA: Risk factors for methotrexate-induced lung injury in patients with rheumatoid arthritis. A multicenter, case-control study. Methotrexate-Lung Study Group. Ann Intern Med 1997, 127:356-364.
  • [232]Kent PD, Luthra HS, Michet C Jr: Risk factors for methotrexate-induced abnormal laboratory monitoring results in patients with rheumatoid arthritis. J Rheumatol 2004, 31:1727-1731.
  • [233]Walker AM, Funch D, Dreyer NA, Tolman KG, Kremer JM, Alarcon GS, Lee RG, Weinblatt ME: Determinants of serious liver disease among patients receiving low-dose methotrexate for rheumatoid arthritis. Arthritis Rheum 1993, 36:329-335.
  • [234]Beyeler C, Jordi B, Gerber NJ, Im Hof V: Pulmonary function in rheumatoid arthritis treated with low-dose methotrexate: a longitudinal study. Br J Rheumatol 1996, 35:446-452.
  • [235]Ito S, Nakazono K, Murasawa A, Mita Y, Hata K, Saito N, Kikuchi M, Yoshida K, Nakano M, Gejyo F: Development of fulminant hepatitis B (precore variant mutant type) after the discontinuation of low-dose methotrexate therapy in a rheumatoid arthritis patient. Arthritis Rheum 2001, 44:339-342.
  • [236]Shergy WJ, Polisson RP, Caldwell DS, Rice JR, Pisetsky DS, Allen NB: Methotrexate-associated hepatotoxicity: retrospective analysis of 210 patients with rheumatoid arthritis. Am J Med 1988, 85:771-774.
  • [237]Phillips CA, Cera PJ, Mangan TF, Newman ED: Clinical liver disease in patients with rheumatoid arthritis taking methotrexate. J Rheumatol 1992, 19:229-233.
  • [238]Furst DE, Koehnke R, Burmeister LF, Kohler J, Cargill I: Increasing methotrexate effect with increasing dose in the treatment of resistant rheumatoid arthritis. J Rheumatol 1989, 16:313-320.
  • [239]Schnabel A, Reinhold-Keller E, Willmann V, Gross WL: Tolerability of methotrexate starting with 15 or 25 mg/week for rheumatoid arthritis. Rheumatol Int 1994, 14:33-38.
  • [240]Verstappen SM, Jacobs JW, van der Veen MJ, Heurkens AH, Schenk Y, ter Borg EJ, Blaauw AA, Bijlsma JW, Utrecht Rheumatoid Arthritis Cohort study group: Intensive treatment with methotrexate in early rheumatoid arthritis: aiming for remission. Computer Assisted Management in Early Rheumatoid Arthritis (CAMERA, an open-label strategy trial). Ann Rheum Dis 2007, 66:1443-1449.
  • [241]Wegrzyn J, Adeleine P, Miossec P: Better efficacy of methotrexate given by intramuscular injection than orally in patients with rheumatoid arthritis. Ann Rheum Dis 2004, 63:1232-1234.
  • [242]Braun J, Kastner P, Flaxenberg P, Wahrisch J, Hanke P, Demary W, von Hinuber U, Rockwitz K, Heitz W, Pichlmeier U, Guimbal-Schmolck C, Brandt A, MC-MTX 6/Rh Study Group: Comparison of the clinical efficacy and safety of subcutaneous versus oral administration of methotrexate in patients with active rheumatoid arthritis: results of a six-month, multicenter, randomized, double-blind, controlled, phase IV trial. Arthritis Rheum 2008, 58:73-81.
  • [243]Morgan SL, Baggott JE, Vaughn WH, Young PK, Austin JV, Krumdieck CL, Alarcon GS: The effect of folic acid supplementation on the toxicity of low-dose methotrexate in patients with rheumatoid arthritis. Arthritis Rheum 1990, 33:9-18.
  • [244]Morgan SL, Baggott JE, Vaughn WH, Austin JS, Veitch TA, Lee JY, Koopman WJ, Krumdieck CL, Alarcon GS: Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. A double-blind, placebo-controlled trial. Ann Intern Med 1994, 121:833-841.
  • [245]Shiroky JB, Neville C, Esdaile JM, Choquette D, Zummer M, Hazeltine M, Bykerk V, Kanji M, St-Pierre A, Robidoux L, Bourque L: Low-dose methotrexate with leucovorin (folinic acid) in the management of rheumatoid arthritis. Results of a multicenter randomized, double-blind, placebo-controlled trial. Arthritis Rheum 1993, 36:795-803.
  • [246]Kremer JM, Furst DE, Weinblatt ME, Blotner SD: Significant changes in serum AST across hepatic histological biopsy grades: prospective analysis of 3 cohorts receiving methotrexate therapy for rheumatoid arthritis. J Rheumatol 1996, 23:459-461.
  • [247]Kremer JM, Alarcon GS, Lightfoot RW Jr, Willkens RF, Furst DE, Williams HJ, Dent PB, Weinblatt ME: Methotrexate for rheumatoid arthritis. Suggested guidelines for monitoring liver toxicity. American College of Rheumatology. Arthritis Rheum 1994, 37:316-328.
  • [248]Gutierrez-Urena S, Molina JF, Garcia CO, Cuellar ML, Espinoza LR: Pancytopenia secondary to methotrexate therapy in rheumatoid arthritis. Arthritis Rheum 1996, 39:272-276.
  • [249]Rau R, Karger T, Herborn G, Frenzel H: Liver biopsy findings in patients with rheumatoid arthritis undergoing longterm treatment with methotrexate. J Rheumatol 1989, 16:489-493.
  • [250]Kremer JM, Lee RG, Tolman KG: Liver histology in rheumatoid arthritis patients receiving long-term methotrexate therapy. A prospective study with baseline and sequential biopsy samples. Arthritis Rheum 1989, 32:121-127.
  • [251]Visser K, van der Heijde D: Incidence of liver enzyme elevations and liver biopsy abnormalities during methotrexate treatment in rheumatoid arthritis: a systematic review of the literature. Arthritis Rheum 2008, 58(Suppl):S557.
  • [252]Ros S, Juanola X, Condom E, Canas C, Riera J, Guardiola J, Del Blanco J, Rebasa P, Valverde J, Roig-Escofet O: Light and electron microscopic analysis of liver biopsy samples from rheumatoid arthritis patients receiving long-term methotrexate therapy. Scand J Rheumatol 2002, 31:330-336.
  • [253]Choi HK, Hernan MA, Seeger JD, Robins JM, Wolfe F: Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study. Lancet 2002, 359:1173-1177.
  • [254]van Halm VP, Nurmohamed MT, Twisk JW, Dijkmans BA, Voskuyl AE: Disease-modifying antirheumatic drugs are associated with a reduced risk for cardiovascular disease in patients with rheumatoid arthritis: a case control study. Arthritis Res Ther 2006, 8:R151. BioMed Central Full Text
  • [255]Salliot C, van der Heijde D: Long-term safety of methotrexate monotherapy in patients with rheumatoid arthritis: a systematic literature research. Ann Rheum Dis 2009, 68:1100-1104.
  • [256]Doran MF, Crowson CS, Pond GR, O'Fallon WM, Gabriel SE: Predictors of infection in rheumatoid arthritis. Arthritis Rheum 2002, 46:2294-2300.
  • [257]Wolfe F, Michaud K: Lymphoma in rheumatoid arthritis: the effect of methotrexate and anti-tumor necrosis factor therapy in 18,572 patients. Arthritis Rheum 2004, 50:1740-1751.
  • [258]Hoshida Y, Xu JX, Fujita S, Nakamichi I, Ikeda J, Tomita Y, Nakatsuka S, Tamaru J, Iizuka A, Takeuchi T, Aozasa K: Lymphoproliferative disorders in rheumatoid arthritis: clinicopathological analysis of 76 cases in relation to methotrexate medication. J Rheumatol 2007, 34:322-331.
  • [259]Katchamart W, Trudeau J, Phumethum V, Bombardier C: Efficacy and toxicity of methotrexate (MTX) monotherapy versus MTX combination therapy with non-biological disease-modifying antirheumatic drugs in rheumatoid arthritis: a systematic review and meta-analysis. Ann Rheum Dis 2009, 68:1105-1112.
  • [260]Tugwell P, Pincus T, Yocum D, Stein M, Gluck O, Kraag G, McKendry R, Tesser J, Baker P, Wells G: Combination therapy with cyclosporine and methotrexate in severe rheumatoid arthritis. The Methotrexate-Cyclosporine Combination Study Group. N Engl J Med 1995, 333:137-141.
  • [261]Capell HA, Madhok R, Porter DR, Munro RA, McInnes IB, Hunter JA, Steven M, Zoma A, Morrison E, Sambrook M, Wui Poon F, Hampson R, McDonald F, Tierney A, Henderson N, Ford I: Combination therapy with sulfasalazine and methotrexate is more effective than either drug alone in patients with rheumatoid arthritis with a suboptimal response to sulfasalazine: results from the double-blind placebo-controlled MASCOT study. Ann Rheum Dis 2007, 66:235-241.
  • [262]Haagsma CJ, van Riel PL, de Jong AJ, van de Putte LB: Combination of sulphasalazine and methotrexate versus the single components in early rheumatoid arthritis: a randomized, controlled, double-blind, 52 week clinical trial. Br J Rheumatol 1997, 36:1082-1088.
  • [263]Dougados M, Combe B, Cantagrel A, Goupille P, Olive P, Schattenkirchner M, Meusser S, Paimela L, Rau R, Zeidler H, Leirisalo-Repo M, Peldan K: Combination therapy in early rheumatoid arthritis: a randomised, controlled, double blind 52 week clinical trial of sulphasalazine and methotrexate compared with the single components. Ann Rheum Dis 1999, 58:220-225.
  • [264]Sany J, Anaya JM, Canovas F, Combe B, Jorgensen C, Saker S, Thaury MN, Gavroy JP: Influence of methotrexate on the frequency of postoperative infectious complications in patients with rheumatoid arthritis. J Rheumatol 1993, 20:1129-1132.
  • [265]Murata K, Yasuda T, Ito H, Yoshida M, Shimizu M, Nakamura T: Lack of increase in postoperative complications with low-dose methotrexate therapy in patients with rheumatoid arthritis undergoing elective orthopedic surgery. Mod Rheumatol 2006, 16:14-19.
  • [266]Ostensen M, Hartmann H, Salvesen K: Low dose weekly methotrexate in early pregnancy. A case series and review of the literature. J Rheumatol 2000, 27:1872-1875.
  • [267]Ostensen M, von Esebeck M, Villiger PM: Therapy with immunosuppressive drugs and biological agents and use of contraception in patients with rheumatic disease. J Rheumatol 2007, 34:1266-1269.
  • [268]Lewden B, Vial T, Elefant E, Nelva A, Carlier P, Descotes J, French Network of Regional Pharmacovigilance C: Low dose methotrexate in the first trimester of pregnancy: results of a French collaborative study. J Rheumatol 2004, 31:2360-2365.
  • [269]Oxford Centre for Evidence Based Medicine - Levels of Evidence [http://www.cebm.net/index.aspx?o=1025] webcite (accessed March 2008)
  文献评价指标  
  下载次数:16次 浏览次数:38次