CAPÍTULO 2: Manejo terapéutico en pacientes con artritis reumatoidea
Resumen
En este apartado se presentan las 21 recomendaciones sobre el tratamiento de pacientes con artritis reumatoidea (AR) que responden a las 71 preguntas PICO (Patient, Intervention, Comparison, Outcome). La mayoría se analizó en forma cuantitativa a través de la metodología GRADE (Sistem Grade of Recommendation, Assessment, Development, and Evaluation). Toda evidencia que no pudo examinarse por GRADE se analizó en forma cualitativa (Material suplementario-apéndice 1-3).Citas
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II. García-Morales JM, Lozada-Mellado M, Hinojosa-Azaola A, Llorente L, Ogata-Medel M, Pineda-Juárez JA, et al. Effect of a dynamic exercise program in combination with Mediterranean diet on quality of life in women with rheumatoid arthritis. J Clinical Rheumatol. 2020;26(7 Suppl 2):S116-22.
III. Sadeghi A, Tabatabaiee M, Mousavi MA, Mousavi SN, Abdollahi Sabet S, Jalili N. Dietary pattern or weight loss: which one is more important to reduce disease activity score in patients with rheumatoid arthritis? A randomized feeding trial. Int J Clin Pract. 2022;2022:6004916.
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V. McKellar G, Morrison E, McEntegart A, Hampson R, Tierney A, Mackle G, et al. A pilot study of a Mediterranean-type diet intervention in female patients with rheumatoid arthritis living in areas of social deprivation in Glasgow. Ann Rheum Diseases. 2007;66(9):1239-43.
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VII. Braun J, Kästner P, Flaxenberg P, Währisch J, Hanke P, Demary W, et al. 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(1):73-81.
VIII. Islam MS, Haq SA, Islam MN, Azad AK, Islam MA, Barua R, et al. Comparative efficacy of subcutaneous versus oral methotrexate in active rheumatoid arthritis. Mymensingh Med J. 2013;22(3):483-8.
IX. Scott DG, Claydon P, Ellis C. Retrospective evaluation of continuation rates following a switch to subcutaneous methotrexate in rheumatoid arthritis patients failing to respond to or tolerate oral methotrexate: the MENTOR study. MENTOR study. Scand J Rheumatol. 2014;43(6):470-6.
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XI. Gottheil S, Thorne JC, Schieir O, Boire G, Haraoui B, Hitchon C, et al. Early use of subcutaneous MTX monotherapy vs. MTX oral or combination therapy significantly delays time to initiating biologics in early RA. Arthritis and Rheumatology. Conference: ACR/ARHP 2016. United states. et al. Conference start: 20161111. 2016;68:4208‐10.
XII. Kim J, Ryu H, Yoo DH, Park SH, Song GG, Park W, et al. A clinical trial and extension study of infliximab in Korean patients with active rheumatoid arthritis despite methotrexate treatment. J Korean Med Sci. 2013;28(12):1716‐22.
XIII. Maini R, St Clair EW, Breedveld F, Furst D, Kalden J, Weisman M, et al. Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group. Lancet. 1999;354(9194):1932-9.
XIV. Lipsky PE, van der Heijde DM, St Clair EW, Furst DE, Breedveld FC, Kalden JR, et al. Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. N Engl J Med. 2000;343(22):1594-602.
XV. Westhovens R, Yocum D, Han J, Berman A, Strusberg I, Geusens P, et al. The safety of infliximab, combined with background treatments, among patients with rheumatoid arthritis and various comorbidities: a large, randomized, placebo-controlled trial. Arthritis Rheum. 2006;54(4):1075-86.
XVI. Maini RN, Breedveld FC, Kalden JR, Smolen JS, Furst D, Weisman MH, et al. Sustained improvement over two years in physical function, structural damage, and signs and symptoms among patients with rheumatoid arthritis treated with infliximab and methotrexate. Arthritis Rheum. 2004;50(4):1051-65.
XVII. van der Heijde D, Klareskog L, Rodriguez-Valverde V, Codreanu C, Bolosiu H, Melo-Gomes J, et al. Comparison of etanercept and methotrexate, alone and combined, in the treatment of rheumatoid arthritis: two-year clinical and radiographic results from the TEMPO study, a double-blind, randomized trial. Arthritis Rheum. 2006;54(4):1063-74.
XVIII. Klareskog L, van der Heijde D, de Jager JP, Gough A, Kalden J, Malaise M, et al. 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(9410):675-81.
XIX. Hobbs K, Deodhar A, Wang B, Bitman B, Nussbaum J, Chung J, et al. Randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of etanercept in patients with moderately active rheumatoid arthritis despite DMARD therapy. Springerplus. 2015;4:113.
XX. Furst DE, Schiff MH, Fleischmann RM, Strand V, Birbara CA, Compagnone D, et al. Adalimumab, a fully human anti tumor necrosis factor-alpha monoclonal antibody, and concomitant standard antirheumatic therapy for the treatment of rheumatoid arthritis: results of STAR (Safety Trial of Adalimumab in Rheumatoid Arthritis). J Rheumatol. 2003;30(12):2563-71.
XXI. Keystone EC, Kavanaugh AF, Sharp JT, Tannenbaum H, Hua Y, Teoh LS, et al. Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial. Arthritis Rheum. 2004;50(5):1400-11.
XXII. Weinblatt ME, Keystone EC, Furst DE, Moreland LW, Weisman MH, Birbara CA, et al. Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum. 2003;48(1):35-45.
XXIII. Keystone EC, Genovese MC, Klareskog L, Hsia EC, Hall ST, Miranda PC, et al. Golimumab, a human antibody to tumour necrosis factor {alpha} given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate therapy: the GO-FORWARD Study. Ann Rheum Dis. 2009;68(6):789-96.
XXIV. Li Z, Zhang F, Kay J, Fei K, Han C, Zhuang Y, et al. Efficacy and safety results from a Phase 3, randomized, placebo-controlled trial of subcutaneous golimumab in Chinese patients with active rheumatoid arthritis despite methotrexate therapy. Int J Rheum Dis. 2016;19(11):1143‐56.
XXV. Tanaka Y, Harigai M, Takeuchi T, Yamanaka H, Ishiguro N, Yamamoto K, et al. Golimumab in combination with methotrexate in Japanese patients with active rheumatoid arthritis: results of the GO-FORTH study. Ann Rheum Dis. 2012;71(6):817-24.
XXVI. Weinblatt ME, Bingham CO, Mendelsohn AM, Kim L, Mack M, Lu J, et al. Intravenous golimumab is effective in patients with active rheumatoid arthritis despite methotrexate therapy with responses as early as week 2: results of the phase 3, randomised, multicentre, double-blind, placebo-controlled GO-FURTHER trial. Ann Rheum Dis. 2013;72(3):381‐9.
XXVII. Conaghan PG, Emery P, Østergaard M, Keystone EC, Genovese MC, Hsia EC, et al. Assessment by MRI of inflammation and damage in rheumatoid arthritis patients with methotrexate inadequate response receiving golimumab: results of the GO-FORWARD trial. Ann Rheum Dis. 2011;70(11):1968-74.
XXVIII. Genovese MC, Han C, Keystone EC, Hsia EC, Buchanan J, Gathany T, et al. Effect of golimumab on patient-reported outcomes in rheumatoid arthritis: results from the GOFORWARD study. J Rheumatol. 2012;39(6):1185-91.
XXIX. Bingham CO, Weinblatt M, Han C, Gathany TA, Kim L, Lo KH, et al. The effect of intravenous golimumab on health-related quality of life in rheumatoid arthritis: 24-week results of the phase III GO-FURTHER trial. J Rheumatol. 2014;41(6):1067‐76.
XXX. Schiff MH, von Kempis J, Goldblum R, Tesser JR, Mueller RB. Rheumatoid arthritis secondary non-responders to TNF can attain an efficacious and safe response by switching to certolizumab pegol: a phase IV, randomised, multicentre, double-blind, 12-week study, followed by a 12-week openlabel phase. Ann Rheum Dis. 2014;73(12):2174‐7.
XXXI. Yamamoto K, Takeuchi T, Yamanaka H, Ishiguro N, Tanaka Y, Eguchi K, et al. Efficacy and safety of certolizumab pegol plus methotrexate in Japanese rheumatoid arthritis patients with an inadequate response to methotrexate: the J-RAPID randomized, placebo-controlled trial. Mod Rheumatol. 2014;24(5):715‐24.
XXXII. Bi L, Li Y, He L, Xu H, Jiang Z, Wang Y, et al. Efficacy and safety of certolizumab pegol in combination with methotrexate in methotrexate-inadequate responder Chinese patients with active rheumatoid arthritis: 24-week results from a randomised, double-blind, placebo-controlled phase 3 study. Clin Exp Rheumatol. 2019;37(2):227‐34.
XXXIII. Kang YM, Park YE, Park W, Choe JY, Cho CS, Shim SC, et al. Rapid onset of efficacy predicts response to therapy with certolizumab plus methotrexate in patients with active rheumatoid arthritis. J Korean Med Sci. 2018;33(6):1224‐33.
XXXIV. Smolen J, Landewé RB, Mease P, Brzezicki J, Mason D, Luijtens K, et al. Efficacy and safety of certolizumab pegol plus methotrexate in active rheumatoid arthritis: the RAPID 2 study. A randomised controlled trial. Ann Rheum Dis. 2009;68(6):797-804.
XXXV. Keystone E, van der Heijde D, Mason D, Jr., Landewé R, Vollenhoven RV, Combe B, et al. Certolizumab pegol plus methotrexate is significantly more effective than placebo plus methotrexate in active rheumatoid arthritis: findings of a fifty-two-week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallelgroup study. Arthritis Rheum. 2008;58(11):3319-29.
XXXVI. Choy E, McKenna F, Vencovsky J, Valente R, Goel N, Vanlunen B, et al. Certolizumab pegol plus MTX administered every 4 weeks is effective in patients with RA who are partial responders to MTX. Rheumatology (Oxford). 2012;51(7):1226-34.
XXXVII. Kivitz A, Olech E, Borofsky M, Zazueta BM, NavarroSarabia F, Radominski SC, et al. Subcutaneous tocilizumab versus placebo in combination with disease-modifying antirheumatic drugs in patients with rheumatoid arthritis. Arthritis Care Res. 2014;66(11):1653‐61.
XXXVIII. Smolen JS, Beaulieu A, Rubbert-Roth A, Ramos-Remus C, Rovensky J, Alecock E, et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebocontrolled, randomised trial. Lancet. 2008;371(9617):987-97.
XXXIX. Genovese MC, McKay JD, Nasonov EL, Mysler EF, da Silva NA, Alecock E, et al. Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: the tocilizumab in combination with traditional diseasemodifying antirheumatic drug therapy study. Arthritis Rheum. 2008;58(10):2968-80.
XL. Baek HJ, Lim MJ, Park W, Park SH, Shim SC, Yoo DH, et al. Efficacy and safety of tocilizumab in Korean patients with active rheumatoid arthritis. J Korean Med Sci. 2019;34(4):917‐31.
XLI. Kremer JM, Blanco R, Brzosko M, Burgos-Vargas R, Halland AM, Vernon E, 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(3):609-21.
XLII. Tanaka Y, Wada K, Takahashi Y, Hagino O, van Hoogstraten H, Graham NMH, et al. Sarilumab plus methotrexate in patients with active rheumatoid arthritis and inadequate response to methotrexate: results of a randomized, placebo-controlled phase III trial in Japan. Arthritis Res Ther. 2019;21(1):79.
XLIII. Genovese MC, Fleischmann R, Kivitz AJ, RellBakalarska M, Martincova R, Fiore S, 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(6):1424-37.
XLIV. Genovese MC, Stanislav M, Van Hoogstraten H, Martincova R, Fan C, Van Adelsberg J. Efficacy of sarilumab plus methotrexate in achieving clinical remission, using 4 different definitions, in patients with active, moderateto-severe rheumatoid arthritis in a phase 3 study. Arthritis Rheumatol. 2015;67(Suppl 10):#2770.
XLV. Strand V, Kosinski M, Chen CI, Joseph G, Rendas-Baum R, Graham NMH, et al. Sarilumab plus methotrexate improves patient-reported outcomes in patients with active rheumatoid arthritis and inadequate responses to methotrexate: results of a phase III trial. Arthritis Res Ther. 2016;18(1):198.
XLVI. Genovese MC, van Adelsberg J, Fan C, Graham NMH, van Hoogstraten H, Parrino J, et al. Two years of sarilumab in patients with rheumatoid arthritis and an inadequate response to MTX: safety, efficacy and radiographic outcomes. Rheumatology (Oxford). 2018;57(8):1423‐31.
XLVII. Matsubara T, Inoue H, Nakajima T, Tanimura K, Sagawa A, Sato Y, et al. Abatacept in combination with methotrexate in Japanese biologic-naive patients with active rheumatoid arthritis: a randomised placebocontrolled phase IV study. RMD Open. 2018;4(2):e000813.
XLVIII. Kremer JM, Westhovens R, Leon M, Di Giorgio E, Alten R, Steinfeld S, et al. Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig. N Engl J Med. 2003;349(20):1907-15.
XLIX. Kremer JM, Genant HK, Moreland LW, Russell AS, Emery P, Abud-Mendoza C, et al. Effects of abatacept in patients with methotrexate-resistant active rheumatoid arthritis: a randomized trial. Ann Intern Med. 2006;144(12):865-76.
L. Schiff M, Keiserman M, Codding C, Songcharoen S, Berman A, Nayiager S, et al. Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: a phase III, multi-centre, randomised, double-blind, placebocontrolled study in patients with rheumatoid arthritis and an inadequate response to methotrexate. Ann Rheum Dis. 2008;67(8):1096-103.
LI. Takeuchi T, Matsubara T, Nitobe T, Suematsu E, Ohta S, Honjo S, et al. Phase II dose-response study of abatacept in Japanese patients with active rheumatoid arthritis with an inadequate response to methotrexate. Mod Rheumatol. 2013;23(2):226-35.
LII. Weinblatt M, Combe B, Covucci A, Aranda R, Becker JC, Keystone E. Safety of the selective costimulation modulator abatacept in rheumatoid arthritis patients receiving background biologic and nonbiologic disease-modifying antirheumatic drugs: A one-year randomized, placebocontrolled study. Arthritis Rheum. 2006;54(9):2807-16.
LIII. Emery P, Kosinski M, Li T, Martin M, Williams GR, Becker JC, et al. Treatment of rheumatoid arthritis patients with abatacept and methotrexate significantly improved health-related quality of life. J Rheumatol. 2006;33(4):681-9.
LIV. Russell AS, Wallenstein GV, Li T, Martin MC, Maclean R, Blaisdell B, et al. Abatacept improves both the physical and mental health of patients with rheumatoid arthritis who have inadequate response to methotrexate treatment. Ann Rheum Dis. 2007;66(2):189-94.
LV. Genovese MC, Covarrubias A, Leon G, Mysler E, Keiserman M, Valente R, et al. Subcutaneous abatacept versus intravenous abatacept: a phase IIIb noninferiority study in patients with an inadequate response to methotrexate. Arthritis Rheumatol. 2011;63(10):2854-64.
LVI. Edwards JC, Szczepanski L, Szechinski J, FilipowiczSosnowska A, Emery P, Close DR, et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med. 2004;350(25):2572-81.
LVII. Emery P, Fleischmann R, Filipowicz-Sosnowska A, Schechtman J, Szczepanski L, Kavanaugh 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(5):1390-400.
LVIII. Emery P, Deodhar A, Rigby WF, Isaacs JD, Combe B, Racewicz AJ, et al. Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebocontrolled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab’s Efficacy in MTX iNadequate rEsponders (SERENE). Ann Rheum Dis. 2010;69(9):1629-35.
LIX. Peterfy C, Emery P, Tak PP, Østergaard M, DiCarlo J, Otsa K, et al. MRI assessment of suppression of structural damage in patients with rheumatoid arthritis receiving rituximab: results from the randomised, placebo-controlled, doubleblind RA-SCORE study. Ann Rheum Dis. 2016;75(1):170‐7.
LX. Mease PJ, Revicki DA, Szechinski J, Greenwald M, Kivitz A, Barile-Fabris L, et al. Improved health-related quality of life for patients with active rheumatoid arthritis receiving rituximab: Results of the Dose-Ranging Assessment: International Clinical Evaluation of Rituximab in Rheumatoid Arthritis (DANCER) Trial. J Rheumatol. 2008;35(1):20-30.
LXI. Strand V, Balbir-Gurman A, Pavelka K, Emery P, Li N, Yin M, et al. Sustained benefit in rheumatoid arthritis following one course of rituximab: improvements in physical function over 2 years. Rheumatology (Oxford). 2006;45(12):1505-13.
LXII. Behrens F, Koehm M, Rossmanith T, Alten R, Aringer M, Backhaus M, et al. Rituximab plus leflunomide in rheumatoid arthritis: a randomized, placebocontrolled, investigator-initiated clinical trial (AMARA study). Rheumatology (Oxford). 2021;60(11):5318‐28.
LXIII. Kremer JM, Bloom BJ, Breedveld FC, Coombs JH, Fletcher MP, Gruben D, et al. The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: Results of a double-blind, placebo-controlled phase IIa trial of three dosage levels of CP-690,550 versus placebo. Arthritis Rheum. 2009;60(7):1895-905.
LXIV. Fleischmann R, Kremer J, Cush J, Schulze-Koops H, Connell CA, Bradley JD, et al. Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. N Engl J Med. 2012;367(6):495-507.
LXV. Kremer JM, Cohen S, Wilkinson BE, Connell CA, French JL, Gomez-Reino J, 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(4):970-81.
LXVI. Kremer J, Li ZG, Hall S, Fleischmann R, Genovese M, Martin-Mola E, et al. Tofacitinib in combination with nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis: a randomized trial. Ann Int Med. 2013;159(4):253‐61.
LXVII. Tanaka Y, Suzuki M, Nakamura H, Toyoizumi S, Zwillich SH. Phase II study of tofacitinib (CP-690,550) combined with methotrexate in patients with rheumatoid arthritis and an inadequate response to methotrexate. Arthritis Care Res (Hoboken). 2011;63(8):1150-8.
LXVIII. van Vollenhoven RF, Fleischmann R, Cohen S, Lee EB, García-Meijide JA, Wagner S, et al. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl J Med. 2012;367(6):508‐19.
LXIX. van der Heijde D, Tanaka Y, Fleischmann R, Keystone E, Kremer J, Zerbini C, et al. Tofacitinib (CP-690,550) in patients with rheumatoid arthritis receiving methotrexate: twelve-month data from a twentyfour-month phase III randomized radiographic study. Arthritis Rheum. 2013;65(3):559‐70.
LXX. Strand V, Kremer JM, Gruben D, Krishnaswami S, Zwillich SH, Wallenstein GV. Tofacitinib in combination with conventional disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis. Patient-reported outcomes from a phase III randomized Controlled Trial. Arthritis Care Res. 2017;69(4):592‐8.
LXXI. Coombs JH, Bloom BJ, Breedveld FC, Fletcher MP, Gruben D, Kremer JM, et al. Improved pain, physical functioning and health status in patients with rheumatoid arthritis treated with CP-690,550, an orally active Janus kinase (JAK) inhibitor: results from a randomised, doubleblind, placebo-controlled trial. Ann Rheum Dis. 2010;69(2):413-6.
LXXII. Burmester GR, Kremer JM, Van den Bosch F, Kivitz A, Bessette L, Li Y, et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (SELECT-NEXT): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018;391(10139):2503‐12.
LXXIII. Kameda H, Takeuchi T, Yamaoka K, Oribe M, Kawano M, Zhou Y, et al. Efficacy and safety of upadacitinib in Japanese patients with rheumatoid arthritis (SELECTSUNRISE): a placebo-controlled phase IIb/III study. Rheumatology (Oxford). 2020;59(11):3303‐13.
LXXIV. Zeng X, Zhao D, Radominski SC, Keiserman M, Lee CK, Meerwein S, et al. Upadacitinib in patients from China, Brazil, and South Korea with rheumatoid arthritis and an inadequate response to conventional therapy. Int J Rheum Dis. 2021;24(12):1530-9.
LXXV. Strand V, Bergman M, Tundia N, Ostor A, Durez P, Song IH, et al. Upadacitinib improves patient-reported outcomes in patients with rheumatoid arthritis and inadequate response to methotrexate: results from select-compare. Ann Rheum Dis. 2019;78:738‐9.
LXXVI. Dougados M, van der Heijde D, Chen YC, Greenwald M, Drescher E, Liu J, 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(1):88‐95.
LXXVII. Fleischmann R, Schiff M, van der Heijde D, RamosRemus C, Spindler A, Stanislav M, et al. Baricitinib, methotrexate, or combination in patients with rheumatoid arthritis and no or limited prior diseasemodifying antirheumatic drug treatment. Arthritis Rheumatol. 2017;69(3):506‐17.
LXXVIII. Keystone EC, Taylor PC, Drescher E, Schlichting DE, Beattie SD, Berclaz PY, et al. Safety and efficacy of baricitinib at 24 weeks in patients with rheumatoid arthritis who have had an inadequate response to methotrexate. Ann Rheum Dis. 2015;74(2):333‐40.
LXXIX. Tanaka Y, Lee CK, Li ZG, Li KJ, Ishii T, Won JE, et al. Baricitinib in East Asian patients with active RA and inadequate response to methotrexate: post hoc subanalysis of the RA-BEAM study. Int J Rheum Dis. 2016;19:187‐8.
LXXX. Genovese M, Keystone E, Taylor P, Drescher E, Berclaz PY, Lee CH, et al. Results of a blinded Phase2b dose-ranging study of baricitinib in combination with traditional disease-modifying antirheumatic drugs in patients with rheumatoid arthritis. Int J Rheum Dis. 2013;16:62.
LXXXI. Emery P, Blanco R, Maldonado Cocco J, Chen YC, Gaich CL, Delozier AM, et al. Patient-reported outcomes from a phase III study of baricitinib in patients with conventional synthetic DMARD-refractory rheumatoid arthritis. RMD open. 2017;3(1):e000410.
LXXXII. Smolen JS, Kremer JM, Gaich CL, DeLozier AM, Schlichting DE, Xie L, et al. Patient-reported outcomes from a randomised phase III study of baricitinib in patients with rheumatoid arthritis and an inadequate response to biological agents (RA-BEACON). Ann Rheum Diseases. 2017;76(4):694-700.
LXXXIII. Emery P, Breedveld FC, Hall S, Durez P, Chang DJ, Robertson D, et al. Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial. Lancet. 2008;372(9636):375-82.
LXXXIV. Breedveld FC, Weisman MH, Kavanaugh AF, Cohen SB, Pavelka K, van Vollenhoven R, et al. The PREMIER study: A multicenter, randomized, doubleblind 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(1):26-37.
LXXXV. Kavanaugh A, Fleischmann RM, Emery P, Kupper H, Redden L, Guerette B, et al. Clinical, functional and radiographic consequences of achieving stable low disease activity and remission with adalimumab plus methotrexate or methotrexate alone in early rheumatoid arthritis: 26-week results from the randomised, controlled OPTIMA study. Ann Rheum Dis. 2013;72(1):64‐71.
LXXXVI. Detert J, Bastian H, Listing J, Weiß A, Wassenberg S, Liebhaber A, et al. Induction therapy with adalimumab plus methotrexate for 24 weeks followed by methotrexate monotherapy up to week 48 versus methotrexate therapy alone for DMARD-naive patients with early rheumatoid arthritis: HIT HARD, an investigator-initiated study. Ann Rheum Dis. 2013;72(6):844‐50.
LXXXVII. Hørslev-Petersen K, Hetland ML, Junker P, Pødenphant J, Ellingsen T, Ahlquist P, et al. Adalimumab added to a treat-to-target strategy with methotrexate and intraarticular triamcinolone in early rheumatoid arthritis increased remission rates, function and quality of life. The OPERA Study: an investigator-initiated, randomised, double-blind, parallel-group, placebocontrolled trial. Ann Rheum Dis. 2014;73(4):654‐61.
LXXXVIII. Emery P, Fleischmann RM, Moreland LW, Hsia EC, Strusberg I, Durez P, et al. Golimumab, a human antitumor necrosis factor alpha monoclonal antibody, injected subcutaneously every four weeks in methotrexate-naive patients with active rheumatoid arthritis: twenty-four-week results of a phase III, multicenter, randomized, double-blind, placebocontrolled study of golimumab before methotrexate as first-line therapy for early-onset rheumatoid arthritis. Arthritis Rheum. 2009;60(8):2272‐83.
LXXXIX. Atsumi T, Yamamoto K, Takeuchi T, Yamanaka H, Ishiguro N, Tanaka Y, et al. The first double-blind, randomised, parallel-group certolizumab pegol study in methotrexate-naive early rheumatoid arthritis patients with poor prognostic factors, C-OPERA, shows inhibition of radiographic progression. Ann Rheum Dis. 2016;75(1):75‐83.
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