Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Perspective
  • Published:

ESSAY

Treat-to-target in rheumatoid arthritis — are we there yet?

Nature Reviews Rheumatology volume 15, pages 180–186 (2019)Cite this article

Subjects

Abstract

Treat-to-target has been established as a guiding principle for the treatment of rheumatoid arthritis (RA) and encompasses several distinct elements: choosing a target and a method for measuring it; assessing the target at a pre-specified time point; a commitment to change the therapy if the target is not achieved; and shared decision-making. A treat-to-target approach yields superior outcomes to standard care in RA, and the ACR, EULAR and other professional organizations have endorsed treat-to-target as a fundamental therapeutic strategy for RA. Nevertheless, data on the degree to which treat-to-target is employed in the clinic are scarce; it seems that although some elements of treat-to-target are widely used, full implementation remains uncommon. Outstanding knowledge gaps to be addressed include how to select the right target for each patient, how often to assess whether the target has been achieved and the selection of each subsequent therapy in an evidence-based manner.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: The meaning of treat-to-target.
Fig. 2: Treat-to-target in the EULAR treatment recommendations for RA.

Similar content being viewed by others

References

  1. Poulter, N. R., Prabhakaran, D. & Caulfield, M. Hypertension. Lancet 386, 801–812 (2015).

    Article  Google Scholar 

  2. Verdecchia, P. et al. Usual versus tight control of systolic blood pressure in non-diabetic patients with hypertension (Cardio-Sis): an open-label randomised trial. Lancet 374, 525–533 (2009).

    Article  Google Scholar 

  3. Nathan, D. M. et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N. Engl. J. Med. 353, 2643–2653 (2005).

    Article  Google Scholar 

  4. Soran, H., Dent, R. & Durrington, P. Evidence-based goals in LDL-C reduction. Clin. Res. Cardiol. 106, 237–248 (2017).

    Article  CAS  Google Scholar 

  5. Smolen, J. S. et al. Treating rheumatoid arthritis to target: recommendations of an international task force. Ann. Rheum. Dis. 69, 631–637 (2010).

    Article  Google Scholar 

  6. Smolen, J. S. et al. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann. Rheum. Dis. 75, 3–15 (2016).

    Article  Google Scholar 

  7. Winthrop, K. L. et al. The unmet need in rheumatology: reports from the targeted therapies meeting 2017. Clin. Immunol. 186, 87–93 (2018).

    Article  CAS  Google Scholar 

  8. Smolen, J. S. et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann. Rheum. Dis. 76, 960–977 (2017).

    Article  Google Scholar 

  9. Singh, J. A. et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 68, 1–26 (2016).

    PubMed  Google Scholar 

  10. Prevoo, M. L. 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. 38, 44–48 (1995).

    Article  CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  12. Smolen, J. S. & Aletaha, D. Scores for all seasons: SDAI and CDAI. Clin. Exp. Rheumatol. 32 (Suppl. 85), S75–S79 (2014).

    Google Scholar 

  13. Anderson, J. K., Zimmerman, L., Caplan, L. & Michaud, K. Measures of rheumatoid arthritis disease activity: Patient (PtGA) and Provider (PrGA) Global Assessment of Disease Activity, Disease Activity Score (DAS) and Disease Activity Score with 28-Joint Counts (DAS28), Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), Patient Activity Score (PAS) and Patient Activity Score-II (PASII), Routine Assessment of Patient Index Data (RAPID), Rheumatoid Arthritis Disease Activity Index (RADAI) and Rheumatoid Arthritis Disease Activity Index-5 (RADAI-5), Chronic Arthritis Systemic Index (CASI), Patient-Based Disease Activity Score With ESR (PDAS1) and Patient-Based Disease Activity Score without ESR (PDAS2), and Mean Overall Index for Rheumatoid Arthritis (MOI-RA). Arthritis Care Res. 63 (Suppl. 11), S14–S36 (2011).

    Article  Google Scholar 

  14. Farheen, K. & Agarwal, S. K. Assessment of disease activity and treatment outcomes in rheumatoid arthritis. J. Manag. Care Pharm. 17 (Suppl. B), S09–S13 (2011).

    PubMed  Google Scholar 

  15. Gaujoux-Viala, C. et al. Evaluating disease activity in rheumatoid arthritis: which composite index is best? A systematic literature analysis of studies comparing the psychometric properties of the DAS, DAS28, SDAI and CDAI. Joint Bone Spine 79, 149–155 (2012).

    Article  Google Scholar 

  16. Bentley, M. J. & Reed, G. W. Simplified composite disease activity measures in rheumatoid arthritis: should they be used in standard care? Clin. Exp. Rheumatol. 26, 358–366 (2008).

    CAS  PubMed  Google Scholar 

  17. Makinen, H., Hannonen, P. & Sokka, T. Definitions of remission for rheumatoid arthritis and review of selected clinical cohorts and randomised clinical trials for the rate of remission. Clin. Exp. Rheumatol. 24 (Suppl. 43), S22–S28 (2006).

    Google Scholar 

  18. Schoels, M., Alasti, F., Smolen, J. S. & Aletaha, D. Evaluation of newly proposed remission cut-points for disease activity score in 28 joints (DAS28) in rheumatoid arthritis patients upon IL-6 pathway inhibition. Arthritis Res. Ther. 19, 155 (2017).

    Article  CAS  Google Scholar 

  19. Hirsh, J. et al. Limited health literacy predicts patient confusion about patient global assessments of disease activity and rheumatoid arthritis model disease states. Arthritis Care Res. https://doi.org/10.1002/acr.23692 (2018).

  20. Canhao, H. et al. Common evaluations of disease activity in rheumatoid arthritis reach discordant classifications across different populations. Front. Med. (Lausanne) 5, 40 (2018).

    Article  Google Scholar 

  21. Ferreira, R. J. O. et al. Drivers of patient global assessment in patients with rheumatoid arthritis who are close to remission: an analysis of 1588 patients. Rheumatology 56, 1573–1578 (2017).

    Article  Google Scholar 

  22. van Nies, J. A. et al. What is the evidence for the presence of a therapeutic window of opportunity in rheumatoid arthritis? A systematic literature review. Ann. Rheum. Dis. 73, 861–870 (2014).

    Article  Google Scholar 

  23. Mottonen, T. et al. Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial. FIN-RACo trial group. Lancet 353, 1568–1573 (1999).

    Article  CAS  Google Scholar 

  24. Pinals, R. S., Masi, A. T. & Larsen, R. A. Preliminary criteria for clinical remission in rheumatoid arthritis. Arthritis Rheum. 24, 1308–1315 (1981).

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  26. Verstappen, S. M. 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. 66, 1443–1449 (2007).

    Article  CAS  Google Scholar 

  27. van Vollenhoven, R. F. et al. Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to methotrexate in patients with early rheumatoid arthritis (SWEFOT trial): 1-year results of a randomised trial. Lancet 374, 459–466 (2009).

    Article  Google Scholar 

  28. Goekoop-Ruiterman, Y. P. et al. Comparison of treatment strategies in early rheumatoid arthritis: a randomized trial. Ann. Intern. Med. 146, 406–415 (2007).

    Article  Google Scholar 

  29. O’Dell, J. R. et al. Therapies for active rheumatoid arthritis after methotrexate failure. N. Engl. J. Med. 369, 307–318 (2013).

    Article  Google Scholar 

  30. Haavardsholm, E. A. et al. Ultrasound in management of rheumatoid arthritis: ARCTIC randomised controlled strategy trial. BMJ 354, i4205 (2016).

    Article  Google Scholar 

  31. Dale, J. et al. Targeting ultrasound remission in early rheumatoid arthritis: the results of the TaSER study, a randomised clinical trial. Ann. Rheum. Dis. 75, 1043–1050 (2016).

    Article  Google Scholar 

  32. Møller-Bisgaard, S. et al. The value of adding MRI to a clinical treat-to-target strategy in rheumatoid arthritis patients in clinical remission: clinical and radiographic outcomes from the IMAGINE-RA randomised controlled trial [abstract]. Ann. Rheum. Dis. 77 (Suppl. 2), A58 (2018).

    Google Scholar 

  33. de Wit, M. P., Smolen, J. S., Gossec, L. & van der Heijde, D. M. Treating rheumatoid arthritis to target: the patient version of the international recommendations. Ann. Rheum. Dis. 70, 891–895 (2011).

    Article  Google Scholar 

  34. Smolen, J. S. et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann. Rheum. Dis. 73, 492–509 (2014).

    Article  CAS  Google Scholar 

  35. Harrold, L. R. et al. Prescribing practices in a US cohort of rheumatoid arthritis patients before and after publication of the American College of Rheumatology treatment recommendations. Arthritis Rheum. 64, 630–638 (2012).

    Article  Google Scholar 

  36. Gvozdenovic, E. et al. When rheumatologists report that they agree with a guideline, does this mean that they practise the guideline in clinical practice? Results of the International Recommendation Implementation Study (IRIS). RMD Open 2, e000221 (2016).

    Article  Google Scholar 

  37. Yu, Z. et al. Implementation of treat-to-target for rheumatoid arthritis in the US: analysis of baseline data from a randomized controlled trial. Arthritis Care Res. 70, 801–806 (2018).

    Article  Google Scholar 

  38. Solomon, D. H. et al. Implementation of treat-to-target in rheumatoid arthritis through a learning collaborative: results of a randomized controlled trial. Arthritis Rheumatol. 69, 1374–1380 (2017).

    Article  Google Scholar 

  39. Felson, D. T. et al. American College of Rheumatology/European League against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Ann. Rheum. Dis. 70, 404–413 (2011).

    Article  Google Scholar 

  40. Hetland, M. L. et al. Aggressive combination therapy with intra-articular glucocorticoid injections and conventional disease-modifying anti-rheumatic drugs in early rheumatoid arthritis: second-year clinical and radiographic results from the CIMESTRA study. Ann. Rheum. Dis. 67, 815–822 (2008).

    Article  CAS  Google Scholar 

  41. Horslev-Petersen, K. et al. Adalimumab added to a treat-to-target strategy with methotrexate and intra-articular triamcinolone in early rheumatoid arthritis increased remission rates, function and quality of life. The OPERA Study: an investigator-initiated, randomised, double-blind, parallel-group, placebo-controlled trial. Ann. Rheum. Dis. 73, 654–661 (2014).

    Article  CAS  Google Scholar 

  42. Glinatsi, D. et al. Head-to-head comparison of aggressive conventional therapy and three biological treatments and comparison of two de-escalation strategies in patients who respond to treatment: study protocol for a multicenter, randomized, open-label, blinded-assessor, phase 4 study. Trials 18, 161 (2017).

    Article  Google Scholar 

  43. Taylor, P. C. et al. Baricitinib versus placebo or adalimumab in rheumatoid arthritis. N. Engl. J. Med. 376, 652–662 (2017).

    Article  CAS  Google Scholar 

  44. van Vollenhoven, R. F. et al. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N. Engl. J. Med. 367, 508–519 (2012).

    Article  Google Scholar 

  45. Fleischmann, R. et al. Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b/4, double-blind, head-to-head, randomised controlled trial. Lancet 390, 457–468 (2017).

    Article  CAS  Google Scholar 

  46. Hambardzumyan, K. et al. A multi-biomarker disease activity score and the choice of second-line therapy in early rheumatoid arthritis after methotrexate failure. Arthritis Rheumatol. 69, 953–963 (2017).

    Article  CAS  Google Scholar 

  47. Porter, D., Dale, J. & Sattar, N. How low to aim in rheumatoid arthritis? Learning from other disciplines. Ann. Rheum. Dis. 73, 480–482 (2014).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Amsterdam University Medical Centers, Amsterdam, Netherlands

    Ronald van Vollenhoven

  2. Amsterdam Rheumatology and Immunology Centre, Amsterdam, Netherlands

    Ronald van Vollenhoven

Authors
  1. Ronald van Vollenhoven
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ronald van Vollenhoven.

Ethics declarations

Competing interests

R.v.V. declares that he has received research support and grants from AbbVie, Bristol Myers Squibb, GlaxoSmithKline, Pfizer and UCB and consultancy fees or honoraria from AbbVie, AstraZeneca, Biogen, Biotest, Bristol Myers Squibb, Celgene, Gilead, GlaxoSmithKline, Janssen, Lilly, Novartis, Pfizer and UCB.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Reviewer information

Nature Reviews Rheumatology thanks S. Proudman, D. Porter and the other anonymous reviewer(s), for their contribution to the peer review of this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

van Vollenhoven, R. Treat-to-target in rheumatoid arthritis — are we there yet?. Nat Rev Rheumatol 15, 180–186 (2019). https://doi.org/10.1038/s41584-019-0170-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41584-019-0170-5

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing