513
Views
15
CrossRef citations to date
0
Altmetric
Original Article

Iguratimod, a synthetic disease modifying anti-rheumatic drug inhibiting the activation of NF-κB and production of RANKL: Its efficacy, radiographic changes, safety and predictors over two years’ treatment for Japanese rheumatoid arthritis patients

&
Pages 418-429 | Received 29 Jun 2017, Accepted 22 May 2018, Published online: 23 Jul 2018

References

  • Smolen JS, Landewé R, Bijlsma J, Burmester G, Chatzidionysiou K, Dougados M, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017;76(6):960–77.
  • Singh JA, Saag KG, Bridges JRSL, Akl EA, Bannuru RR, Sullivan MC, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2016;68(1):1–25.
  • Shahouri SH, Michaud K, Mikuls TR, Caplan L, Shaver TS, Anderson JD, et al. Remission of rheumatoid arthritis in clinical practice: application of the American College of Rheumatology/European League Against Rheumatism 2011 remission criteria. Arthritis Rheum. 2011;63(11):3204–15.
  • Souto A, Maneiro JR, Gómez-Reino JJ. Rate of discontinuation and drug survival of biologic therapies in rheumatoid arthritis: a systematic review and meta-analysis of drug registries and health care databases. Rheumatology (Oxford). 2016;55(3):523–34.
  • Tanaka K, Shimotori T, Makino S, Aikawa Y, Inaba T, Yoshida C, et al. Pharmacological studies of the new antiinflammatory agent 3-formylamino-7-methylsulfonylamino-6-phenoxy 4H-1-benzopyran-4-one. 1st communication: antiinflammatory, analgesic and other related properties. Arzneim-Forsch/Drug Res. 1992;42(7):935–44.
  • Tanaka K, Kawasaki H, Kurata K, Aikawa Y, Tsukamoto Y, Inaba T. T-614, a novel antirheumatic drug, inhibits both the activity and induction of cyclooxygenase-2 (COX-2) in cultured fibroblasts. Jpn J Pharmacol. 1995;67(4):305–14.
  • Kawakami A, Tsuboi M, Urayama S, Matsuoka N, Yamasaki S, Hida A, et al. Inhibitory effect of a new anti-rheumatic drug T-614 on costimulatory molecule expression, cytokine production, and antigen presentation by synovial cells. J Lab Clin Med. 1999;133(6):566–74.
  • Yamamoto M, Urata N, Yamamoto T, Aikawa Y, Funaki J, Tanaka K. Effect of a disease-modifying antirheumatic drug iguratimod (T-614) on inflammatory cytokine production. Jpn Pharmacol Ther. 2007;35(6):551–9.
  • Tanaka K, Aikawa Y, Kawasaki H, Asaoka K, Inaba T, Yoshida C. Pharmacological studies on 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-one (T-614), a novel antiinflammatory agent. 4th communication: inhibitory effect on the production of interleukin-1 and interleukin-6. J Pharmacobio-Dyn. 1992;15(11):649–55.
  • Kohno M, Aikawa Y, Tsubouchi Y, Hashiramoto A, Yamada R, Kawahito Y, et al. Inhibitory effect of T-614 on tumor necrosis factor-alpha induced cytokine production and nuclear factor-kappaB activation in cultured human synovial cells. J Rheumatol. 2001;28(12):2591–6.
  • Aikawa Y, Yamamoto M, Yamamoto T, Morimoto K, Tanaka K. An anti-rheumatic agent T-614 inhibits NF-κB activation in LPS- and TNF-α-stimulated THP-1 cells without interfering with IκBα degradation. Inflamm Res. 2002;51(4):188–94.
  • Du F, Lü LJ, Fu Q, Dai M, Teng JL, Fan W, et al. T-614, a novel immunomodulator, attenuates joint inflammation and articular damage in collagen-induced arthritis. Arthritis Res Ther. 2008;10(6):R136.
  • Tanaka K, Yamamoto T, Aikawa Y, Kizawa K, Muramoto K, Matsuno H, et al. Inhibitory effects of an anti-rheumatic agent T-614 on immunoglobulin production by cultured B cells and rheumatoid synovial tissues engrafted into SCID mice. Rheumatology (Oxford). 2003;42(11):1365–71.
  • Tanaka K, Shimotori T, Taniguchi Y, Eguchi M, Abe C. Pharmacological studies on T-614, a novel antiinflammatory agent: effect on type II collagen-induced arthritis in DBA/1J mice and spontaneous arthritis in MRL/1 mice. Int J Immunotherapy. 1993;9(2):69–78.
  • Kuriyama K, Higuchi C, Tanaka K, Yoshikawa H, Itoh K. A novel anti-rheumatic drug, T-614, stimulates osteoblastic differentiation in vitro and bone morphogenetic protein-2-induced bone formation in vivo. Biochem Biophys Res Commun. 2002;299(5):903–9.
  • Du F, Lü LJ, Teng JL, Shen N, Ye P, Bao CD. T-614 alters the production of matrix metalloproteinases (MMP-1 andMMP-3) and inhibits the migratory expansion of rheumatoid synovial fibroblasts, in vitro. Int Immunopharmacol. 2012;13(1):54–60.
  • Wei Y, Sun X, Hua M, Tan W, Wang F, Zhang M. Inhibitory effect of a novel antirheumatic drug T-614 on the IL-6-induced RANKL/OPG, IL-17, and MMP-3 expression in synovial fibroblasts from rheumatoid arthritis patients. BioMed Res Int. 2015;2015:214683.
  • Hara M, Abe T, Sugawara S, Mizushima Y, Hoshi K, Irimajiri S, et al. Efficacy and safety of iguratimod compared with placebo and salazosulfapyridine in active rheumatoid arthritis: a controlled, multicenter, double-blind, parallel-group study. Mod Rheumatol. 2007;17(1):1–9.
  • Ishiguro N, Yamamoto K, Katayama K, Kondo M, Sumida T, Mimori T, et al. Concomitant iguratimod therapy in patients with active rheumatoid arthritis despite stable doses of methotrexate a randomized, double-blind, placebo-controlled trial. Mod Rheumatol. 2013;23(3):430–9.
  • Lu LJ, Bao CD, Dai M, Teng JL, Fan W, Du F, et al. Multicenter, randomized, double-blind, controlled trial of treatment of active rheumatoid arthritis with T-614 compared with methotrexate. Arthritis Rheum. 2009;61(7):979–87.
  • Mimori T, Harigai M, Atsumi T, Fujii T, Kuwana M, Matsuno H, et al. Safety and effectiveness of 24-week treatment with iguratimod, a new oral disease-modifying drug, for patient with rheumatoid arthritis: interim analysis of post-marketing surveillance study of 2679 patients in Japan. Mod Rheumatol. 2017;27(5):755–65.
  • Hara M, Abe T, Sugawara S, Mizushima Y, Hoshi K, Irimajiri S, et al. Long-term safety study of iguratimod in patients with rheumatoid arthritis. Mod Rheumatol. 2007;17(1):10–6.
  • Hara M, Ishiguro N, Katayama K, Kondo M, Sumida T, Mimori T, Iguratimod-Clinical Study group, et al. Safety and efficacy of combination therapy of iguratimod with methotrexate for patients with active rheumatoid arthritis with an inadequate response to methotrexate: an open-level extension of a randomized, double-blind, placebo-controlled trial. Mod Rheumatol. 2014;24(3):410–8.
  • Okamura K, Yonemoto Y, Suto T, Okura C, Takagishi K. Efficacy at 52 weeks of daily clinical use of iguratimod in patients with rheumatoid arthritis. Mod Rheumatol. 2015;25:534–9.
  • Li J, Mao H, Liang Y, Lu Y, Chen S, Yang N, et al. Efficacy and safety of iguratimod for the treatment of rheumatoid arthritis. Clin Dev Immunol. 2013;2013:310628.
  • Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO, III, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569–81.
  • Fransen J, Creemers MCW, van Riel PLCM. Remission in rheumatoid arthritis: agreement of the disease activity score (DAS28) with the ARA preliminary remission criteria. Rheumatology (Oxford). 2004;43(10):1252–5.
  • Smolen JS, Breedveld FC, Schiff MH, Kalden JR, Emery P, Eberl G, et al. A simplified disease activity index for rheumatoid arthritis for use in clinical practice. Rheumatology (Oxford). 2003;42(2):244–57.
  • Anderson J, Caplan L, Yazdany J, Robbins ML, Neogi T, Michaud K, et al. Rheumatoid arthritis disease activity measures: American College of Rheumatology recommendations for use in clinical practice. Arthritis Care Res. 2012;64(5):640–7.
  • Welsing PMJ, van Riel PLCM. The Nijmegen inception cohort of early rheumatoid arthritis. J Rheumatol Suppl. 2004;69:14–21.
  • Genant HK, Jiang Y, Peterfy C, Lu Y, Redei J, Countryman PJ. Assessment of rheumatoid arthritis using a modified scoring method on digitized and original radiographs. Arthritis Rheum. 1998;41(9):1583–90.
  • Genant HK, Peterfy CG, Westhovens R, Becker JC, Aranda R, Vratsanos G, et al. Abatacept inhibits progression of structural damage in rheumatoid arthritis: results from the long-term extension of the AIM trial. Ann Rheum Dis. 2008;67(8):1084–9.
  • Kremer JM, Peterfy C, Russel AS, Emery P, Abud-Mendoza C, Sibilia J, et al. Longterm safety, efficacy, and inhibition of structural damage progression over 5 years of treatment with abatacept in patients with rheumatoid arthritis in the abatacept in inadequate responders to methotrexate trial. J Rheumatol. 2014;41(6):1077–87.
  • Dougados M, Kissel K, Conaghan PG, Mola EM, Schett G, Gerli R, et al. Clinical, radiographic and immunogenic effects after 1 year of tocilizumab-based treatment strategies in rheumatoid arthritis: the ACT-RAY study. Ann Rheum Dis. 2014;73(5):803–9.
  • Shrout PE, Fleiss JL. Intraclass correlations: uses in assessing rater reliability. Psychol Bull. 1979;86(2):420–8.
  • Van der Heijde D, Boers M, Lassere M. Methodological issues in radiographic scoring methods in rheumatoid arthritis. J Rheumatol. 1999;26(3):726–30.
  • Bruynesteyn K, Boers M, Kostense P, van der Linden S, van der Heijde D. Deciding on progression of joint damage in paired films of individual patients: smallest detectable difference or change. Ann Rheum Dis. 2005;64(2):179–82.
  • Woodworth TG, Furst DE, Strand V, Kempeni J, Fenner H, Lau CS, et al. Standardizing assessment of adverse effects in rheumatology clinical trials: status of OMERACT toxicity working group March 2000: towards a common understanding of comparative toxicity/safety profiles for antirheumatic therapies. J Rheumatol. 2001;28:1163–9.
  • Ishikawa K, Sakaguchi M. SA 96 (N-(2-mercapto-2-methylpropanoyl)-L-cysteine) in rheumatoid arthritis. Scand J Rheumatol. 1986;15(1):85–90.
  • Chatham WW. Traditional disease-modifying antirheumatic drugs: gold compounds, D-penicillamine, sulfasalazine, and antimalarials. In: Koopman WJ, Moreland LW, editors. Arthritis and Allied Conditions, A Textbook of Rheumatology. 15th ed. Philadelphia: Lippincott Williams & Wilkins; 2005. p. 915–44.
  • Ichikawa Y, Saito T, Yamanaka H, Akizuki M, Kondo H, Kobayashi S, et al. Therapeutic effects of the combination of methotrexate and bucillamine in early rheumatoid arthritis: a multicenter, double-blind, randomized controlled study. Mod Rheumatol. 2005;15(5):323–8.
  • Matsuno H, Okada M, Sakai Y, Abe C, Katayama K, Sagawa A, et al. The usefulness of a new triple combination treatment utilizing methotrexate. salazosulfapyridine, and bucillamine in rheumatoid arthritis. Mod Rheumatol. 2016;26(1):51–6.
  • Tanaka E, Inoue E, Kawaguchi Y, Tomatsu T, Yamanaka H, Hara M, et al. Acceptability and usefulness of mizoribine in the management of rheumatoid arthritis in methotrexate-refractory patients and elderly patients, based on analysis of data from a large-scale observational cohort study. Mod Rheumatol. 2006;16(4):214–9.
  • Horikoshi M, Ito S, Ishikawa M, Umeda N, Kondo Y, Tsuboi H, et al. Efficacy of mizoribine pulse therapy in patients with rheumatoid arthritis who show a reduced or insufficient response to infliximab. Mod Rheumatol. 2009;19(3):229–34.
  • Kremer JM, Habros JS, Kolba KS, Kaine JL, Borton MA, Mengle-Gaw LJ, for the Tacrolimus-Methotrexate Rheumatoid Arthritis Study Group, et al. Tacrolimus in rheumatoid arthritis patients receiving concomitant methotrexate: a six-month, open-label study. Arthritis Rheum. 2003;48(10):2763–8.
  • Yocum DE, Furst DE, Kaine JL, Baldassare AR, Stevenson JT, Borton MA, for the Tacrolimus Rheumatoid Arthritis Study Group, et al. Efficacy and safety of tacrolimus in patients with rheumatoid arthritis: a double-blind trial. Arthritis Rheum. 2003;48(12):3328–37.
  • Nakajima A, Inoue E, Taniguchi A, Momohara S, Yamanaka H. Effectiveness of tacrolimus in comparison with methotrexate or biologics in propensity score-matched patients with rheumatoid arthritis. Mod Rheumatol. 2016;26(6):836–43.
  • Fujisawa K, Aono H, Hasunuma T, Yamamoto K, Mita S, Nishioka K. Activation of transcription factor NF-κB in human synovial cells in response to tumor necrosis factor α. Arthritis Rheum. 1996;39(2):197–203.
  • Yarilina A, Xu K, Chan C, Ivashkiv LB. Regulation of inflammatory responses in tumor necrosis factor-activated and rheumatoid arthritis synovial macrophages by Janus kinase inhibitors. Arthritis Rheum. 2012;64(12):3856–66.
  • Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 1998;93(2):165–76.
  • Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA. 1998;95(7):3597–602.
  • Kotake S, Udagawa N, Takahashi N, Matsuzaki K, Itoh K, Ishiyama S, et al. IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest. 1999;103(9):1345–52.
  • Lee CK, Lee EY, Chung SM, Mun SH, Yoo B, Moon HB. Effects of disease-modifying antirheumatic drugs and antiinflammatory cytokines on human osteoclastogenesis through interaction with receptor activator of nuclear factor kappaB, osteoprotegerin, and receptor activator of nuclear factor kappaB ligand. Arthritis Rheum. 2004;50(12):3831–43.
  • Hashizume M, Hayakawa N, Mihara M. IL-6 trans-signaling directly induces RANKL on fibroblast-like synovial cells and is involved in RANKL induction by TNF-α and IL-17. Rheumatology (Oxford). 2008;47(11):1635–40.
  • LaBranche TP, Jesson MI, Radi ZA, Storer CE, Guzova JA, Bonar SL, et al. JAX inhibition with tofacitinib suppresses arthritic joint structural damage through decreased RANKL production. Arthritis Rheum. 2012;64(11):3531–42.
  • Yeo L, Toellner KM, Salmon M, Filer A, Buckley CD, Raza K, et al. Cytokine mRNA profiling identifies B cells as a major source of RANKL in rheumatoid arthritis. Ann Rheum Dis. 2011;70(11):2022–8.
  • Meednu N, Zhang H, Owen T, Sun W, Wang V, Cistrone C, et al. Production of RANKL by memory B cells: a link between B cells and bone erosion in rheumatoid arthritis. Arthritis Rheum. 2016;68(4):805–16.
  • Kostenuik PJ, Nguyen HQ, McCabe J, Warmington KS, Kurahara C, Sun N, et al. Denosumab, a fully human monoclonal antibody to RANKL, inhibits bone resorption and increases BMD in knock-in mice that express chimeric (murine/human) RANKL. J Bone Miner Res. 2009;24(2):182–95.
  • Takeuchi T, Tanaka Y, Ishiguro N, Yamanaka H, Yoneda T, Ohira T, et al. Effect of denosumab on Japanese patients with rheumatoid arthritis: a dose-response study of AMG 162 (Denosumab) in patients with rheumatoid arthritis on methotrexate to validate inhibitory effect on bone erosion (DRIVE) – a 12-month, multicentre, randomised, double-blind, placebo-controlled, phase II clinical trial. Ann Rheum Dis. 2016;75(6):983–90.
  • Majumdar S, Aggarwal BB. Methotrexate suppresses NF-kappaB activation through inhibition of IkappaBalpha phosphorylation and degradation. J Immunol. 2001;167(5):2911–20.
  • Spurlock IIICF, Tossberg JT, Matlock BK, Olsen NJ, Aune TM. Methotrexate inhibits NF-κB activity via long intergenic (noncoding) RNA-p21 induction. Arthritis Rheum. 2014;66(11):2947–57.
  • Yang J-P, Merin JP, Nakano T, Kato T, Kitade Y, Okamoto T. Inhibition of the DNA-binding activity of NF-kappa B by gold compounds in vitro. FEBS Lett. 1995;361(1):89–96.
  • Smolen JS, Kalden JR, Scott DL, Rozman B, Kvien TK, Larsen A, the European leflunomide study group, et al. Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomised, multicentre trial. Lancet. 1999;353(9149):259–66.
  • Choy EHS, Scott DL, Kingsley GH, Williams P, Wojtulewski J, Papasavvas G, et al. Treating rheumatoid arthritis early with disease modifying drugs reduces joint damage: a randomized double blind trial of sulphasalazine vs diclofenac sodium. Clin Exp Rheumatol. 2002;20:351–8.
  • Shergy WJ, Isern RA, Cooley DA, Harshbarger JL, Huffstutter JE, Hughes GM, The prompt study group, et al. Open label study to assess infliximab safety and timing of onset of clinical benefit among patients with rheumatoid arthritis. J Rheumatol. 2002;29:667–77.
  • Baumgartner SW, Fleischmann RM, Moreland LW, Schiff MH, Markenson J, Whitmore JB. Etanercept (Enbrel) in patients with rheumatoid arthritis with recent onset versus established disease: improvement in disability. J Rheumatol. 2004;31:1532–7.
  • 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.
  • Nishimoto N, Hashimoto J, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, et al. Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): evidence of clinical and radiographic benefit from an x ray reader-blinded randomized controlled trial of tocilizumab. Ann Rheum Dis. 2007;66(9):1162–7.
  • Kubo S, Nakayamada S, Nakano K, Hirata S, Fukuyo S, Miyagawa I, et al. Comparison of the efficacies of abatacept and tocilizumab in patients with rheumatoid arthritis by propensity score matching. Ann Rheum Dis. 2016;75:1321–7.
  • Bingham CO, III, Mendelsohn AM, Kim L, Xu Z, Leu J, Han C, on behalf of the GO-Further investigators, et al. Maintenance of clinical and radiographic benefit with intravenous golimumab therapy in patients with active rheumatoid arthritis despite methotrexate therapy week-112 efficacy and safety results of the open-label long-term extension of a phase III, double-blind, randomized, placebo-controlled trial. Arthritis Care Res (Hoboken). 2015;67(12):1627–36.
  • Combe B, Furst DE, Keystone EC, van der Heijde D, Luijtens K, Ionescu L, et al. Certolizumab pegol efficacy across methotrexate regimens: a pre-specified analysis of two phase III trials. Arthritis Care Res (Hoboken). 2016;68(3):299–307.
  • Van der Heijde D, Tanaka Y, Fleischmann R, Keystone E, Kremer J, Zerbini C, and the ORAL scan investigators, et al. Tofacitinib (CP-690, 550) in patients with rheumatoid arthritis receiving methotrexate: twelve-month data from a twenty-four-month phase III randomized radiographic study. Arthritis Rheum. 2013;65(3):559–70.
  • Tanaka Y, Takeuchi T, Yamanaka H, Nakamura H, Toyoizumi S, Zwillich S. Efficacy and safety of tofacitinib as monotherapy in Japanese patients with active rheumatoid arthritis: a 12-week, randomized, phase 2 study. Mod Rheumatol. 2015;25(4):514–21.
  • Schipper LG, Fransen J, den Broeder AA, van Riel PLCM. Time to achieve remission determines time to be in remission. Arthritis Res Ther. 2010;12(3):R97.
  • Van der Heijde D, Keystone EC, Curtis JR, Landewé RB, Schiff MH, Khanna D, et al. Timing and magnitude of initial change in disease activity score 28 predicts the likelihood of achieving low disease activity at 1 year in rheumatoid arthritis patients treated with certolizumab pegol: a post-hoc analysis of the RAPID1 trial. J Rheumatol. 2012;39:1326–33.
  • Curtis JR, McVie T, Mikuls TR, Reynolds RJ, Navarro-Millán I, O’Dell J, et al. Clinical response within 12 weeks as a predictor of future low disease activity in patients with early RA: results from the TEAR Trial. J Rheumatol. 2013;40(5):572–8.
  • White D, Pahau H, Duggan E, Paul S, Thomas R. Trajectory of intensive treat-to-target disease modifying drug regimen in an observational study of an early rheumatoid arthritis cohort. BMJ Open. 2013;3(7):e003083.
  • Kuriya B, Xiong J, Boire G, Haraoui B, Hitchon C, Pope J, for the CATCH investigators, et al. Earlier time to remission predicts sustained clinical remission in early rheumatoid arthritis: results from the Canadian early arthritis cohort (CATCH). J Rheumatol. 2014;41:2161–6.
  • Grigor C, Capell H, Stirling A, McMahon AD, Lock P, Vallance R, et al. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial. Lancet. 2004;364(9430):263–9.
  • Schipper LG, Vermeer M, Kuper HH, Hoekstra MO, Haagsma CJ, den Broeder AA, et al. A tight control treatment strategy aiming for remission in early rheumatoid arthritis is more effective than usual care treatment in daily clinical practice: a study of two cohorts in the Dutch Rheumatoid Arthritis Monitoring registry. Ann Rheum Dis. 2012;71(6):845–50.
  • Rantalaiho V, Kautiainen H, Korpela M, Hannonen P, Kaipiainen-Seppänen O, Möttönen T, for the NEO-RACo study group, et al. Targeted treatment with a combination of traditional DMARDs produces excellent clinical and radiographic long-term outcomes in early rheumatoid arthritis regardless of initial infliximab: the 5-year follow-up results of a randomised clinical trial, the NEO-RACo trial. Ann Rheum Dis. 2014;73(11):1954–61.
  • Smith RT, Peak WP, Kron KM, Hermann IF, DelToro RA, Goldman M. Increasing the effectiveness of gold therapy in rheumatoid arthritis. J Am Med Assoc. 1958;167(10):1197–204.
  • Tak PP. A personalized medicine approach to biologic treatment of rheumatoid arthritis: a preliminary treatment algorithm. Rheumatology (Oxford). 2012;51(4):600–9.
  • De Punder YMR, Jansen TLTA, van Ede AE, den Broeder AA, van Riel PLCM, Fransen J. Personalizing treatment targets in rheumatoid arthritis by using a simple prediction model. J Rheumatol. 2015;42(3):398–404.
  • Isaacs JD, Ferraccioli G. The need for personalised medicine for rheumatoid arthritis. Ann Rheum Dis. 2011;70(1):4–7.
  • Van der Heijde D, Klareskog L, Landewé R, Bruyn GAW, Cantagrel A, Durez P, for the TEMPO study investigators, et al. Disease remission and sustained halting of radiographic progression with combination etanercept and methotrexate in patients with rheumatoid arthritis. Arthritis Rheum. 2007;56(12):3928–39.
  • Hoekstra M, van Ede AE, Haagsma CJ, van de Laar MAFJ, Huizinga TWJ, Kruijsen MWM, et al. Factors associated with toxicity, final dose, and efficacy of methotrexate in patients with rheumatoid arthritis. Ann Rheum Dis. 2003;62(5):423–6.
  • 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(1):22–9.
  • Kroot EJA, de Jong BAW, van Leeuwen MA, Swinkels H, van den Hoogen FHJ, van’t HOF M, et al. The prognostic value of anti-cyclic citrullinated peptide antibody in patients with recent-onset rheumatoid arthritis. Arthritis Rheum. 2000;43(8):1831–5.
  • Gremese E, Salaffi F, Bosello SL, Ciapetti A, Bobbio-Pallavicini F, Caporali R, et al. Very early rheumatoid arthritis as a predictor of remission: a multicentre real life prospective study. Ann Rheum Dis. 2013;72(6):858–62.
  • Boers M. Understanding the window of opportunity concept in early rheumatoid arthritis. Arthritis Rheum. 2003;48(7):1771–4.
  • Luukkainen R, Kajander A, Isomäki H. Effect of gold on progression of erosions in rheumatoid arthritis: better results with early treatment. Scand J Rheum. 1977;6(3):189–92.
  • Gottenberg JE, Ravaud P, Cantagrel A, Combe B, Flipo RM, Schaeverbeke T, et al. Positivity for anti-cyclic citrullinated peptide is associated with a better response to abatacept: data from the ‘Orencia and Rheumatoid Arthritis’ registry. Ann Rheum Dis. 2012;71(11):1815–9.
  • Buch MH, Smolen JS, Betteridge N, Breedveld FC, Burmester G, Dörner T, for the rituximab consensus expert committee, et al. Updated consensus statement on the use of rituximab in patients with rheumatoid arthritis. Ann Rheum Dis. 2011;70:909–20.
  • Harigai M, Ishiguro N, Inokuma S, Mimori T, Ryu J, Takei S, et al. Postmarketing surveillance of the safety and effectiveness of abatacept in Japanese patients with rheumatoid arthritis. Mod Rheumatol. 2016;26(4),491–98.
  • Lindqvist E, Eberhardt K, Bendtzen K, Heinegård D, Saxne T. Prognostic laboratory markers of joint damage in rheumatoid arthritis. Ann Rheum Dis. 2005;64(2):196–201.
  • Courvoisier N, Dougados M, Cantagrel A, Goupille P, Meyer O, Sibilia J, et al. Prognostic factors of 10-year radiographic outcome in early rheumatoid arthritis: a prospective study. Arthritis Res Ther. 2008;10(5):R106.
  • Hetland ML, Stengaard-Pedersen K, Junker P, Østergaard M, Ejbjerg BJ, Jacobsen S, the CIMESTRA study group, et al. 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(10):1789–95.
  • Wang SY, Liu YY, Ye H, Guo JP, Li R, Liu X, et al. Circulating dickkopf-1 is correlated with bone erosion and inflammation in rheumatoid arthritis. J Rheumatol. 2011;38(5):821–7.
  • Vliet Vlieland TPM, Buitenhuis NA, van Zeben D, Vandenbroucke JP, Breedveld FC, Hazes JMW. Sociodemographic factors and the outcome of rheumatoid arthritis in young women. Ann Rheum Dis. 1994;53(12):803–6.
  • Strehl C, Bijlsma JWJ, de Wit M, Boers M, Caeyers N, Cutolo M, et al. Defining conditions where long-term glucocorticoid treatment has an acceptably low level of harm to facilitate implementation of existing recommendations: viewpoints from an EULAR task force. Ann Rheum Dis. 2016;75(6):952–7.
  • De Jong PH, Hazes JM, Barendregt PJ, Huisman M, van Zeben D, van der Lubbe PA, et al. Induction therapy with a combination of DMARDs is better than methotrexate monotherapy: first results of the tREACH trial. Ann Rheum Dis. 2013;72(1):72–8.
  • Breedveld FC, Weisman MH, Kavanaugh AF, Cohen SB, Pavelka K, van Vollenhoven R, for the PREMIER investigators, et al. The PREMIER study: a multicenter, randomized double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum. 2006;54(1):26–37.
  • 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.
  • Kaneko Y, Atsumi T, Tanaka Y, Inoo M, Kobayashi-Haraoka H, Amano K, et al. Comparison of adding tocilizumab to methotrexate with switching to tocilizumab in patients with rheumatoid arthritis with inadequate response to methotrexate: 52-week results from a prospective, randomised, controlled study (SURPRISE study). Ann Rheum Dis. 2016;0:1–7.
  • Lipsky PE, van der Heijde DMFM, St. Clair EW, Furst DE, Breedveld FC, Kalden JR, for the anti-tumor necrosis factor trial in rheumatoid arthritis with concomitant therapy study group, et al. Infliximab and methotrexate in the treatment of rheumatoid arthritis. N Engl J Med. 2000;343(22):1594–602.
  • Yamamoto T, Hasegawa K, Onoda M, Tanaka K. Pharmacokinetic and pharmacodynamic analysis of drug-drug interactions between iguratimod and warfarin. Yakugaku Zasshi. 2016;136(6):905–11.
  • Felson DT, Smolen JS, Wells G, Zhang B, van Tuyl LHD, Funovits J, et al. American College of Rheumatology/European League Against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Arthritis Rheum. 2011;63(3):573–86.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.