Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force

Josef S Smolen, Ferdinand C Breedveld, Gerd R Burmester, Vivian Bykerk, Maxime Dougados, Paul Emery, Tore K Kvien, M Victoria Navarro-Compán, Susan Oliver, Monika Schoels, Marieke Scholte-Voshaar, Tanja Stamm, Michaela Stoffer, Tsutomu Takeuchi, Daniel Aletaha, Jose Louis Andreu, Martin Aringer, Martin Bergman, Neil Betteridge, Hans Bijlsma, Harald Burkhardt, Mario Cardiel, Bernard Combe, Patrick Durez, Joao Eurico Fonseca, Alan Gibofsky, Juan J Gomez-Reino, Winfried Graninger, Pekka Hannonen, Boulos Haraoui, Marios Kouloumas, Robert Landewe, Emilio Martin-Mola, Peter Nash, Mikkel Ostergaard, Andrew Östör, Pam Richards, Tuulikki Sokka-Isler, Carter Thorne, Athanasios G Tzioufas, Ronald van Vollenhoven, Martinus de Wit, Desirée van der Heijde, Josef S Smolen, Ferdinand C Breedveld, Gerd R Burmester, Vivian Bykerk, Maxime Dougados, Paul Emery, Tore K Kvien, M Victoria Navarro-Compán, Susan Oliver, Monika Schoels, Marieke Scholte-Voshaar, Tanja Stamm, Michaela Stoffer, Tsutomu Takeuchi, Daniel Aletaha, Jose Louis Andreu, Martin Aringer, Martin Bergman, Neil Betteridge, Hans Bijlsma, Harald Burkhardt, Mario Cardiel, Bernard Combe, Patrick Durez, Joao Eurico Fonseca, Alan Gibofsky, Juan J Gomez-Reino, Winfried Graninger, Pekka Hannonen, Boulos Haraoui, Marios Kouloumas, Robert Landewe, Emilio Martin-Mola, Peter Nash, Mikkel Ostergaard, Andrew Östör, Pam Richards, Tuulikki Sokka-Isler, Carter Thorne, Athanasios G Tzioufas, Ronald van Vollenhoven, Martinus de Wit, Desirée van der Heijde

Abstract

Background: Reaching the therapeutic target of remission or low-disease activity has improved outcomes in patients with rheumatoid arthritis (RA) significantly. The treat-to-target recommendations, formulated in 2010, have provided a basis for implementation of a strategic approach towards this therapeutic goal in routine clinical practice, but these recommendations need to be re-evaluated for appropriateness and practicability in the light of new insights.

Objective: To update the 2010 treat-to-target recommendations based on systematic literature reviews (SLR) and expert opinion.

Methods: A task force of rheumatologists, patients and a nurse specialist assessed the SLR results and evaluated the individual items of the 2010 recommendations accordingly, reformulating many of the items. These were subsequently discussed, amended and voted upon by >40 experts, including 5 patients, from various regions of the world. Levels of evidence, strengths of recommendations and levels of agreement were derived.

Results: The update resulted in 4 overarching principles and 10 recommendations. The previous recommendations were partly adapted and their order changed as deemed appropriate in terms of importance in the view of the experts. The SLR had now provided also data for the effectiveness of targeting low-disease activity or remission in established rather than only early disease. The role of comorbidities, including their potential to preclude treatment intensification, was highlighted more strongly than before. The treatment aim was again defined as remission with low-disease activity being an alternative goal especially in patients with long-standing disease. Regular follow-up (every 1-3 months during active disease) with according therapeutic adaptations to reach the desired state was recommended. Follow-up examinations ought to employ composite measures of disease activity that include joint counts. Additional items provide further details for particular aspects of the disease, especially comorbidity and shared decision-making with the patient. Levels of evidence had increased for many items compared with the 2010 recommendations, and levels of agreement were very high for most of the individual recommendations (≥9/10).

Conclusions: The 4 overarching principles and 10 recommendations are based on stronger evidence than before and are supposed to inform patients, rheumatologists and other stakeholders about strategies to reach optimal outcomes of RA.

Keywords: Disease Activity; Early Rheumatoid Arthritis; Outcomes research; Rheumatoid Arthritis; Treatment.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Figures

Figure 1
Figure 1
Algorithm of treating rheumatoid arthritis (RA) to target based on the updated recommendations provided in the table 1 and discussed in detail in the 'Results' section. Indicated as separate threads are the main target (remission and sustained remission) and the alternative target (low-disease activity in patients with long-term disease and sustained low-disease activity), but the approaches to attain the targets and sustain them are essentially identical. Adaptation of therapy should be usually done by performing control examinations with appropriate frequency and using composite disease activity measures that comprise joint counts, but should take comorbidities and other patient factors into account. Setting the target as well start and adaptation of therapy should be done as a shared decision with the patient.

References

    1. Van der Heijde DMFM, van't Hof M, van Riel PL, et al. . Development of a Disease activity score based on judgement in clinical practice by rheumatologists. J Rheumatol 1993;20:579–81.
    1. Prevoo MLL, van't Hof MA, Kuper HH, et al. . Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995;38:44–8. 10.1002/art.1780380107
    1. Smolen JS, Breedveld FC, Schiff MH, et al. . A simplified disease activity index for rheumatoid arthritis for use in clinical practice. Rheumatology 2003;42:244–57. 10.1093/rheumatology/keg072
    1. Felson DT, Anderson JJ, Boers M, et al. . American College of Rheumatology preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum 1995;38:727–35. 10.1002/art.1780380602
    1. Aletaha D, Nell VPK, Stamm T, et al. . Acute phase reactants add little to composite disease activity indices for rheumatoid arthritis: validation of a clinical activity score. Arthritis Res 2005;7:R796–806. 10.1186/ar1740
    1. van der Heide A, Jacobs JW, Bijlsma JW, et al. . The effectiveness of early treatment with “second-line” antirheumatic drugs. A randomized, controlled trial. Ann Intern Med 1996;124:699–707. 10.7326/0003-4819-124-8-199604150-00001
    1. Lard LR, Visser H, Speyer I, et al. . Early versus delayed treatment in patients with recent-onset rheumatoid arthritis: comparison of two cohorts who received different treatment strategies. Am J Med 2001;111:446–51. 10.1016/S0002-9343(01)00872-5
    1. Nell V, Machold KP, Eberl G, et al. . Benefit of very early referral and very early therapy with disease-modifying anti-rheumatic drugs in patients with early rheumatoid arthritis. Rheumatology (Oxford) 2004;43:906–14. 10.1093/rheumatology/keh199
    1. Emery P, Salmon M. Early rheumatoid arthritis: time to aim for remission? Ann Rheum Dis 1995;54:944–7. 10.1136/ard.54.12.944
    1. Luukkainen R, Kajander A, Isomaki H. Treatment of rheumatoid arthritis. Br Med J 1978;2:1501 10.1136/bmj.2.6150.1501-c
    1. Smolen JS, Han C, Van der Heijde DM, et al. . Radiographic changes in rheumatoid arthritis patients attaining different disease activity states with methotrexate monotherapy and infliximab plus methotrexate: the impacts of remission and TNF-blockade. Ann Rheum Dis 2009;68:823–7. 10.1136/ard.2008.090019
    1. Lukas C, van der HD, Fatenajad S, et al. . Repair of erosions occurs almost exclusively in damaged joints without swelling. Ann Rheum Dis 2010;69:851–5. 10.1136/ard.2009.119156
    1. Pincus T, Yazici Y, Sokka T, et al. . Methotrexate as the “anchor drug” for the treatment of early rheumatoid arthritis. Clin Exp Rheumatol 2003;21(Suppl 31):S178–85.
    1. Visser K, van der Heijde D. Optimal dosage and route of administration of methotrexate in rheumatoid arthritis: a systematic review of the literature. Ann Rheum Dis 2009;68:1094–9. 10.1136/ard.2008.092668
    1. van Ede AE, Laan RF, Rood MJ, et al. . 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;44:1515–24. 10.1002/1529-0131(200107)44:7<1515::AID-ART273>;2-7
    1. Grigor C, Capell H, Stirling A, et al. . Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial. Lancet 2004;364:263–9. 10.1016/S0140-6736(04)16676-2
    1. Verstappen SMM, Jacobs JWG, van der Venn MJ, et al. . 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;66:1443–9. 10.1136/ard.2007.071092
    1. Vermeer M, Kuper HH, Bernelot Moens HJ, et al. . Adherence to a treat-to-target strategy in early rheumatoid arthritis: results of the DREAM remission induction cohort. Arthritis Res Ther 2012;14:R254 10.1186/ar4099
    1. Smolen JS, Aletaha D, Bijlsma JW, et al. . Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis 2010;69:631–7. 10.1136/ard.2009.123919
    1. Singh JA, Furst DE, Bharat A, et al. . 2012 update of the 2008 american college of rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken) 2012;64:625–39. 10.1002/acr.21641
    1. Smolen JS, Landewe R, Breedveld FC, et al. . EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis 2010;69:964–75. 10.1136/ard.2009.126532
    1. Smolen JS, Landewe R, Breedveld FC, et al. . EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis 2014;73:492–509. 10.1136/annrheumdis-2013-204573
    1. Wollenhaupt J, Albrecht K, Kruger K, et al. . The new 2012 German recommendations for treating rheumatoid arthritis: differences compared to the European standpoint. Z Rheumatol 2013;72:6–9. 10.1007/s00393-012-1093-6
    1. Cardiel MH, Diaz-Borjon A, Vazquez del Mercado EM, et al. . Update of the Mexican College of Rheumatology guidelines for the pharmacologic treatment of rheumatoid arthritis. Reumatol Clin 2014;10:227–40. 10.1016/j.reuma.2013.10.006
    1. Klarenbeek NB, Koevoets R, Van der Heijde DM, et al. . Association with joint damage and physical functioning of nine composite indices and the 2011 ACR/EULAR remission criteria in rheumatoid arthritis. Ann Rheum Dis 2011;70:1815–21. 10.1136/ard.2010.149260
    1. Radner H, Smolen JS, Aletaha D. Remission in rheumatoid arthritis: benefit over low disease activity in patient reported outcomes and costs. Arthritis Res Ther 2014;16:R56 10.1186/ar4491
    1. Linde L, Sorensen J, Ostergaard M, et al. . Does clinical remission lead to normalization of EQ-5D in patients with rheumatoid arthritis and is selection of remission criteria important? J Rheumatol 2010;37:285–90. 10.3899/jrheum.090898
    1. Felson DT, Smolen JS, Wells G, et al. . American college of rheumatology/european league against rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Ann Rheum Dis 2011;70:404–13. 10.1136/ard.2011.149765
    1. Porter D, Dale J, Sattar N. How low to aim in rheumatoid arthritis? Learning from other disciplines. Ann Rheum Dis 2014;73:480–2. 10.1136/annrheumdis-2013-204339
    1. Solomon DH, Bitton A, Katz JN, et al. . Review: treat to target in rheumatoid arthritis: fact, fiction, or hypothesis? Arthritis Rheumatol 2014;66:775–82. 10.1002/art.38323
    1. Waimann Christian A, Citero G, Dal Pra F, et al. . Adherence to a Treat-to-Target (T2T) strategy in early rheumatoid arthritis. Is it feasible in daily clinical practice? Arthritis Rheum 2014;66(Suppl):S1037.
    1. Haraoui B, Smolen JS, Aletaha D, et al. . Treating rheumatoid arthritis to target: multinational recommendations assessment questionnaire. Ann Rheum Dis 2011;70:1999–2002. 10.1136/ard.2011.154179
    1. Stoffer MA, Schoels M, Smolen JS, et al. . Evidence for treating rheumatoid arthritis to target—a systematic literature research informing the treat-to-target task force. Ann Rheum Dis 2015; in press.
    1. Schoels M, Knevel R, Aletaha D, et al. . Evidence for treating rheumatoid arthritis to target: results of a systematic literature search. Ann Rheum Dis 2010;69:638–43. 10.1136/ard.2009.123976
    1. van Eijk IC, Nielen MM, van dH-B, et al. . Aggressive therapy in patients with early arthritis results in similar outcome compared with conventional care: the STREAM randomized trial. Rheumatology (Oxford) 2012;51:686–94. 10.1093/rheumatology/ker355
    1. Schipper LG, Vermeer M, Kuper HH, 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;71:845–50. 10.1136/annrheumdis-2011-200274
    1. Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Kerstens PJ, et al. . DAS-driven therapy versus routine care in patients with recent-onset active rheumatoid arthritis. Ann Rheum Dis 2010;69:65–9. 10.1136/ard.2008.097683
    1. Soubrier M, Lukas C, Sibilia J, et al. . Disease activity score-driven therapy versus routine care in patients with recent-onset active rheumatoid arthritis: data from the GUEPARD trial and ESPOIR cohort. Ann Rheum Dis 2011;70:611–15. 10.1136/ard.2010.137695
    1. Gullick NJ, Oakley SP, Zain A, et al. . Goal-directed therapy for RA in routine practice is associated with improved function in patients with disease duration up to 15 years. Rheumatology (Oxford) 2012;51:759–61. 10.1093/rheumatology/ker399
    1. Pope JE, Haraoui B, Rampakakis E, et al. . Treating to a target in established active rheumatoid arthritis patients receiving a tumor necrosis factor inhibitor: results from a real-world cluster-randomized adalimumab trial. Arthritis Care Res (Hoboken) 2013;65:1401–9. 10.1002/acr.22010
    1. Dougados M, Devauchelle-Pensec V, Ferlet JF, et al. . The ability of synovitis to predict structural damage in rheumatoid arthritis: a comparative study between clinical examination and ultrasound. Ann Rheum Dis 2013;72:665–71. 10.1136/annrheumdis-2012-201469
    1. Dale J, Striling A, McInnes IB, et al. . Targeting ultrasound remission in early rheumatoid arthritis—results of the Taser study. Arthritis Rheum 2013;65(Suppl):S338–9.
    1. Thiele K, Huscher D, Bischoff S, et al. . Performance of the 2011 ACR/EULAR preliminary remission criteria compared with DAS28 remission in unselected patients with rheumatoid arthritis. Ann Rheum Dis 2013;72:1194–9. 10.1136/annrheumdis-2012-201821
    1. Provan SA, Semb AG, Hisdal J, et al. . Remission is the goal for cardiovascular risk management in patients with rheumatoid arthritis: a cross-sectional comparative study. Ann Rheum Dis 2011;70:812–17. 10.1136/ard.2010.141523
    1. Balsa A, de Miguel E, Castillo C, et al. . Superiority of SDAI over DAS-28 in assessment of remission in rheumatoid arthritis patients using power Doppler ultrasonography as a gold standard. Rheumatology (Oxford) 2010;49:683–90. 10.1093/rheumatology/kep442
    1. Sakellariou G, Scire CA, Verstappen SM, et al. . In patients with early rheumatoid arthritis, the new ACR/EULAR definition of remission identifies patients with persistent absence of functional disability and suppression of ultrasonographic synovitis. Ann Rheum Dis 2013;72:245–9. 10.1136/annrheumdis-2012-201817
    1. Gronning K, Rodevand E, Steinsbekk A. Paid work is associated with improved health-related quality of life in patients with rheumatoid arthritis. Clin Rheumatol 2010;29:1317–22. 10.1007/s10067-010-1534-z
    1. Stucki G, Cieza A, Geyh S, et al. . ICF Core Sets for rheumatoid arthritis. J Rehabil Med 2004;(44 Suppl):87–93. 10.1080/16501960410015470
    1. van Tuyl LH, Felson DT, Wells G, et al. . Evidence for predictive validity of remission on long-term outcome in rheumatoid arthritis: A systematic review. Arthritis Care Res (Hoboken) 2010;62:108–17. 10.1002/acr.20021
    1. Gartner M, Mandl P, Radner H, et al. . Sonographic joint assessment in rheumatoid arthritis: associations with clinical joint assessment in remission. Arthritis Rheum 2013;65:2005–14. 10.1002/art.38016
    1. Wakefield RJ, D'Agostino MA, Naredo E, et al. . After treat-to-target: can a targeted ultrasound initiative improve RA outcomes? Ann Rheum Dis 2012;71:799–803. 10.1136/annrheumdis-2011-201048
    1. van der Heijde D. Remission by imaging in rheumatoid arthritis: should this be the ultimate goal? Ann Rheum Dis 2012;71(Suppl 2):i89–92. 10.1136/annrheumdis-2011-200797
    1. Aletaha D, Smolen JS. The definition and measurement of disease modification in inflammatory rheumatic diseases. Rheum Dis Clin North Am 2006;32:9–44. 10.1016/j.rdc.2005.09.005
    1. Makinen H, Kautiainen H, Hannonen P, et al. . Is DAS28 an appropriate tool to assess remission in rheumatoid arthritis? Ann Rheum Dis 2005;64:1410–3. 10.1136/ard.2005.037333
    1. van der Heijde D, Klareskog L, Boers M, et al. . Comparison of different definitions to classify remission and sustained remission: 1 year TEMPO results. Ann Rheum Dis 2005;64:1582–7. 10.1136/ard.2004.034371
    1. Smolen JS, Aletaha D. Interleukin-6 receptor inhibition with tocilizumab and attainment of disease remission in rheumatoid arthritis: the role of acute-phase reactants. Arthritis Rheum 2011;63:43–52. 10.1002/art.27740
    1. Aletaha D, Smolen JS. Joint damage in rheumatoid arthritis progresses in remission according to the Disease Activity Score in 28 joints and is driven by residual swollen joints. Arthritis Rheum 2011;63:3702–11. 10.1002/art.30634
    1. Radner H, Alasti F, Smolen JS, et al. . Time in remission is important for improvement of physical function in patients with rheumatoid arthritis (RA). Arthritis Rheum 2012;64(Suppl):S1104–5.
    1. Koevoets R, van der Heijde D. Being in remission or in low disease activity in rheumatoid arthritis: different meaning with the use of different composite scores. Arthritis Rheum 2009;60(Suppl):957.
    1. Mierau M, Schoels M, Gonda G, et al. . Assessing remission in clinical practice. Rheumatology 2007;46:975–9. 10.1093/rheumatology/kem007
    1. Smolen JS, Wollenhaupt J, Durez P, et al. . Time to achieve remission and sustained remission for MTX-naïve patients with early RA treated with abatacept plus mtx versus mtx alone in the agree trial. Ann Rheum Dis 2013;72(Suppl 3):455–6. 10.1136/annrheumdis-2013-eular.1369
    1. Aletaha D, Ward MM, Machold KP, et al. . Remission and active disease in rheumatoid arthritis: defining criteria for disease activity states. Arthritis Rheum 2005;52:2625–36. 10.1002/art.21235
    1. Bakker MF, Jacobs JW, Verstappen SM, et al. . Tight control in the treatment of rheumatoid arthritis: efficacy and feasibility. Ann Rheum Dis 2007;66(Suppl 3):iii56–60. 10.1136/ard.2007.078360
    1. Kavanaugh A, Fleischmann RM, Emery P, 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;72:64–71. 10.1136/annrheumdis-2011-201247
    1. Fleischmann R, van der Heijde D, Koenig AS, et al. How much does Disease Activity Score in 28 joints ESR and CRP calculations underestimate Disease Activity compared with the Simplified Disease Activity Index? Ann Rheum Dis. 2014 doi: 10.1136/annrheumdis-2013-204920. Published Online First 20 Aug 2014. doi: 10.1136/annrheumdis-2013-204920.
    1. Food and Drug Administration. Guidance for Industry—Rheumatoid arthritis: Developing drug products for treatment. Draft Gudance May 2013. (accessed 5 Oct 2013).
    1. Van der Heijde DM, van Riel PL, van Leeuwen MA, et al. . Prognostic factors for radiographic damage and physical disability in early rheumatoid arthritis. A prospective follow-up study of 147 patients. Br J Rheumatol 1992;31:519–25. 10.1093/rheumatology/31.8.519
    1. van Leeuwen MA, Van der Heijde DM, van Rijswijk MH, et al. . Interrelationship of outcome measures and process variables in early rheumatoid arthritis. A comparison of radiologic damage, physical disability, joint counts, and acute phase reactants. J Rheumatol 1994;21:425–9.
    1. Smolen JS, van der Heijde DMFM, St.Clair EW, et al. . Predictors of joint damage in patients with early rheumatoid arthritis treated with high-dose methotrexate without or with concomitant infliximab. Results from the ASPIRE trial. Arthritis Rheum 2006;54:702–10. 10.1002/art.21678
    1. Klarenbeek NB, Guler-Yuksel M, Van der Heijde DM, et al. . Clinical synovitis in a particular joint is associated with progression of erosions and joint space narrowing in that same joint, but not in patients initially treated with infliximab. Ann Rheum Dis 2010;69:2107–13. 10.1136/ard.2010.131201
    1. Aletaha D, Landewe R, Karonitsch T, et al. . Reporting disease activity in clinical trials of patients with rheumatoid arthritis: EULAR/ACR collaborative recommendations. Ann Rheum Dis 2008;67:1360–4. 10.1136/ard.2008.091454
    1. Pincus T, Swearingen CJ, Bergman M, et al. . RAPID3 (Routine Assessment of Patient Index Data 3), a rheumatoid arthritis index without formal joint counts for routine care: proposed severity categories compared to disease activity score and clinical disease activity index categories. J Rheumatol 2008;35:2136–47. 10.3899/jrheum.080182
    1. Curtis JR, Koetse W, Tambiah J, et al. . Prediction of week 52 treatment response based on a week 12 assessment in rheumatoid arthritis patients receiving certolizumab pegol: comparison of a patient-reported instrument versus physician-based disease activity assessment. Arthritis Rheum 2013;65:S186–7. 10.1002/art.37732
    1. Navarro-Compan V, Gherghe AM, Smolen JS, et al. . Relationship between disease activity indices and their individual components and radiographic progression in RA: a systematic literature review. Rheumatology 2014. [Epub ahead of print 20 Nov 2014]. 10.1093/rheumatology/keu413
    1. Listing J, Kekow J, Manger B, et al. . Mortality in rheumatoid arthritis: the impact of disease activity, treatment with glucocorticoids, TNFalpha inhibitors and rituximab. Ann Rheum Dis 2015;74:415–2110.1136/annrheumdis-2013-204021.
    1. Simard JF, Neovius M, Askling J. Mortality rates in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors: drug-specific comparisons in the Swedish Biologics Register. Arthritis Rheum 2012;64:3502–10. 10.1002/art.34582
    1. Westlake SL, Colebatch AN, Baird J, et al. . Tumour necrosis factor antagonists and the risk of cardiovascular disease in patients with rheumatoid arthritis: a systematic literature review. Rheumatology (Oxford) 2011;50:518–31. 10.1093/rheumatology/keq316
    1. Choi HK, Hernan MA, Seeger JD, et al. . Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study. Lancet 2002;359:1173–7. 10.1016/S0140-6736(02)08213-2
    1. Westlake SL, Colebatch AN, Baird J, et al. . The effect of methotrexate on cardiovascular disease in patients with rheumatoid arthritis: a systematic literature review. Rheumatology (Oxford) 2010;49:295–307. 10.1093/rheumatology/kep366
    1. Tutuncu Z, Reed G, Kremer J, et al. . Do patients with older-onset rheumatoid arthritis receive less aggressive treatment? Ann Rheum Dis 2006;65:1226–9. 10.1136/ard.2005.051144
    1. Bathon JM, Fleischmann RM, van der HD, et al. . Safety and efficacy of etanercept treatment in elderly subjects with rheumatoid arthritis. J Rheumatol 2006;33:234–43.
    1. Koller MD, Aletaha D, Funovits J, et al. . Response of elderly patients with rheumatoid arthritis to methotrexate or TNF inhibitors compared with younger patients. Rheumatology (Oxford) 2009;48:1575–80. 10.1093/rheumatology/kep291
    1. Aletaha D, Funovits J, Smolen JS. Physical disability in rheumatoid arthritis is associated with cartilage damage rather than bone destruction. Ann Rheum Dis 2011;70:733–9. 10.1136/ard.2010.138693
    1. Radner H, Smolen JS, Aletaha D. Impact of comorbidity on physical function in patients with rheumatoid arthritis. Ann Rheum Dis 2010;69:536–41. 10.1136/ard.2009.118430
    1. Radner H, Smolen JS, Aletaha D. Comorbidity affects all domains of physical function and quality of life in patients with rheumatoid arthritis. Rheumatology (Oxford) 2011;50:381–8. 10.1093/rheumatology/keq334
    1. van den Hoek J, Roorda LD, Boshuizen HC, et al. . Long-term physical functioning and its association with somatic comorbidity and comorbid depression in patients with established rheumatoid arthritis: a longitudinal study. Arthritis Care Res (Hoboken) 2013;65:1157–65. 10.1002/acr.21950
    1. Aletaha D, Funovits J, Keystone EC, et al. . Disease activity early in the course of treatment predicts response to therapy after one year in rheumatoid arthritis patients. Arthritis Rheum 2007;56:3226–35. 10.1002/art.22943
    1. van der Heijde D, Keystone EC, Curtis JR, 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 RAPID 1 trial. J Rheumatol 2012;39:1326–33. 10.3899/jrheum.111171
    1. Soubrier M, Puechal X, Sibilia J, et al. . Evaluation of two strategies (initial methotrexate monotherapy vs its combination with adalimumab) in management of early active rheumatoid arthritis: data from the GUEPARD trial. Rheumatology (Oxford) 2009;48:1429–34. 10.1093/rheumatology/kep261
    1. Aletaha D, Funovits J, Breedveld FC, et al. . Rheumatoid arthritis joint progression in sustained remission is determined by disease activity levels preceding the period of radiographic assessment. Arthritis Rheum 2009;60:1242–9. 10.1002/art.24433
    1. Molenaar E, Voskuyl AE, Dinant HJ, et al. . Progression of radiologic damage in patients with rheumatoid arthritis in clinical remission. Arthritis Rheum 2004;50:36–42. 10.1002/art.11481
    1. Smolen JS, Nash P, Durez P, et al. . Maintenance, reduction, or withdrawal of etanercept after treatment with etanercept and methotrexate in patients with moderate rheumatoid arthritis (PRESERVE): a randomised controlled trial. Lancet 2013;381:918–29. 10.1016/S0140-6736(12)61811-X
    1. Takeuchi T, Matsubara T, Ohta S, et al. . Biologic-free remission of established rheumatoid arthritis after discontinuation of abatacept: a prospective, multicentre, observational study in Japan. Rheumatology (Oxford) 2015;54:683–9110.1093/rheumatology/keu338.
    1. Tanaka Y, Takeuchi T, Mimori T, et al. . Discontinuation of infliximab after attaining low disease activity in patients with rheumatoid arthritis: RRR (remission induction by Remicade in RA) study. Ann Rheum Dis 2010;69:1286–91. 10.1136/ard.2009.121491
    1. Tanaka Y, Hirata S, Kubo S, et al. . Discontinuation of adalimumab after achieving remission in patients with established rheumatoid arthritis: 1-year outcome of the HONOR study. Ann Rheum Dis 2015;74:389–9510.1136/annrheumdis-2013-204016.
    1. Saleem B, Keen H, Goeb V, et al. . Patients with RA in remission on TNF blockers: when and in whom can TNF blocker therapy be stopped? Ann Rheum Dis 2010;69:1636–42. 10.1136/ard.2009.117341
    1. Tanaka Y, Hirata S, Saleem B, et al. . Discontinuation of biologics in patients with rheumatoid arthritis. Clin Exp Rheumatol 2013;31(4 Suppl 78):S22–7.
    1. van der Woude D, Visser K, Klarenbeek NB, et al. . Sustained drug-free remission in rheumatoid arthritis after DAS-driven or non-DAS-driven therapy: a comparison of two cohort studies. Rheumatology (Oxford) 2012;51:1120–8. 10.1093/rheumatology/ker516
    1. Emery P, Hammoudeh M, Fitzgerald O, et al. . Assessing maintenance of remission with reduced dose etanercept plus methotrexate, methotrexate alone, or placebo in patients with early rheumatoid arthritis who achieved remission with etanercept and methotrextate: the PRIZE study. Ann Rheum Dis 2013;72(Suppl 3):399 10.1136/annrheumdis-2013-203485
    1. Smolen JS, Emery P, Fleischmann R, et al. . Adjustment of therapy in rheumatoid arthritis on the basis of achievement of stable low disease activity with adalimumab plus methotrexate or methotrexate alone: the randomised controlled OPTIMA trial. Lancet 2014;383:321–32. 10.1016/S0140-6736(13)61751-1
    1. Fautrel B, Gandjbakhch F, Foltz V, et al. . Targeting the lowest efficacious dose for rheumatoid arthritis patients in remission: clinical and structural impact of a stepdown strategy trial based on progressive spacing of TNF-blocker injections (STRASS trial). Ann Rheum Dis 2013;72(Suppl 3):72 10.1136/annrheumdis-2013-eular.271
    1. Smolen JS, van der Heijde D, Machold KP, et al. . Proposal for a new nomenclature of disease-modifying antirheumatic drugs. Ann Rheum Dis 2014;73:3–5. 10.1136/annrheumdis-2013-204317
    1. ten Wolde S, Breedveld FC, Hermans J, et al. . Randomised placebo-controlled study of stopping second-line drugs in rheumatoid arthritis. Lancet 1996;347:347–52. 10.1016/S0140-6736(96)90535-8
    1. Contreras-Yanez I, Ponce De LS, Cabiedes J, et al. . Inadequate therapy behavior is associated to disease flares in patients with rheumatoid arthritis who have achieved remission with disease-modifying antirheumatic drugs. Am J Med Sci 2010;340:282–90. 10.1097/MAJ.0b013e3181e8bcb0
    1. Goodacre LJ, Goodacre JA. Factors influencing the beliefs of patients with rheumatoid arthritis regarding disease-modifying medication. Rheumatology (Oxford) 2004;43:583–6. 10.1093/rheumatology/keh116
    1. Fraenkel L, Peters E, Charpentier P, et al. . Decision tool to improve the quality of care in rheumatoid arthritis. Arthritis Care Res (Hoboken) 2012;64:977–85. 10.1002/acr.21657
    1. Viller F, Guillemin F, Briancon S, et al. . Compliance to drug treatment of patients with rheumatoid arthritis: a 3 year longitudinal study. J Rheumatol 1999;26:2114–22.
    1. De Wit M, Smolen JS, Gossec L, et al. . Treating rheumatoid arthritis to target: The patient version of the international recommendations. Ann Rheum Dis 2011;70:891–5. 10.1136/ard.2010.146662
    1. Dougados M, Betteridge N, Burmester GR, et al. . EULAR standardised operating procedures for the elaboration, evaluation, dissemination, and implementation of recommendations endorsed by the EULAR standing committees. Ann Rheum Dis 2004;63:1172–6. 10.1136/ard.2004.023697
    1. Putrik P, Ramiro S, Kvien TK, et al. . Inequities in access to biologic and synthetic DMARDs across 46 European countries. Ann Rheum Dis 2014;73:198–206. 10.1136/annrheumdis-2012-202603
    1. Putrik P, Ramiro S, Kvien TK, et al. . Variations in criteria regulating treatment with reimbursed biologic DMARDs across European countries. Are differences related to country's wealth? Ann Rheum Dis 2014;73:2010–21. 10.1136/annrheumdis-2013-203819
    1. Bakker MF, Jacobs JW, Welsing PM, et al. . Low-dose prednisone inclusion in a methotrexate-based, tight control strategy for early rheumatoid arthritis: a randomized trial. Ann Intern Med 2012;156:329–39. 10.7326/0003-4819-156-5-201203060-00004
    1. Woodburn J, Hennessy K, Steultjens MP, et al. . Looking through the ‘window of opportunity’: is there a new paradigm of podiatry care on the horizon in early rheumatoid arthritis? J Foot Ankle Res 2010;3:8 10.1186/1757-1146-3-8
    1. Allaart CF, Lems WF, Huizinga TW. The BeSt way of withdrawing biologic agents. Clin Exp Rheumatol 2013;31(4 Suppl 78):S14–18.
    1. Heimans L, Wevers-de Boer KV, Visser K, et al. . A two-step treatment strategy trial in patients with early arthritis aimed at achieving remission: the IMPROVED study. Ann Rheum Dis 2014;73:1356–61. 10.1136/annrheumdis-2013-203243
    1. Nam JL, Villeneuve E, Hensor EM, et al. . Remission induction comparing infliximab and high-dose intravenous steroid, followed by treat-to-target: a double-blind, randomised, controlled trial in new-onset, treatment-naive, rheumatoid arthritis (the IDEA study). Ann Rheum Dis 2014;73:75–85. 10.1136/annrheumdis-2013-203440
    1. Nam JL, Villeneuve E, Hensor EM, et al. . A randomised controlled trial of etanercept and methotrexate to induce remission in early inflammatory arthritis: the EMPIRE trial. Ann Rheum Dis 2014;73:1027–36. 10.1136/annrheumdis-2013-204882
    1. Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, et al. . Comparison of treatment strategies in early rheumatoid arthritis: a randomized trial. Ann Intern Med 2007;146:406–15. 10.7326/0003-4819-146-6-200703200-00005
    1. Nasonov EL, Karateev DE. Does Russia need a treat-to-target initiative? Rheumatology (Oxford) 2015;54:381–2. 10.1093/rheumatology/keu156

Source: PubMed

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