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.

  • Opinion
  • Published:

The need to define treatment goals for systemic lupus erythematosus

Nature Reviews Rheumatology volume 10, pages 567–571 (2014)Cite this article

Subjects

Abstract

In the current therapeutic climate, mortality rates from systemic lupus erythematosus (SLE) remain unacceptably high. Although new therapies are on the horizon, pending their emergence and availability, optimization of the currently available therapies is potentially achievable. A 'treat-to-target' approach is now considered routine for many diseases, including rheumatoid arthritis, for which it has substantially improved patient outcomes. The heterogeneity of SLE, as well as lack of universal agreement over methods to measure disease activity and treatment responses, has impeded the development of such an approach for this disease. In this article, the potential benefits of a treatment-target definition are explored, obstacles to the development of a treatment target in SLE are identified, and possible strategies to achieve this goal are discussed.

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

Figure 1
Figure 2: The phenotypic diversity of active and inactive SLE.

Similar content being viewed by others

References

  1. Uramoto, K. M. et al. Trends in the incidence and mortality of systemic lupus erythematosus, 1950–1992. Arthritis Rheum. 42, 46–50 (1999).

    Article  CAS  Google Scholar 

  2. Mak, A., Cheung, M. W., Chiew, H. J., Liu, Y. & Ho, R. C. Global trend of survival and damage of systemic lupus erythematosus: meta-analysis and meta-regression of observational studies from the 1950s to 2000s. Semin. Arthritis Rheum. 41, 830–839 (2012).

    Article  Google Scholar 

  3. Cook, C. D., Wedgewood, R. J., Craig, J. M., Hartmann, J. R. & Janeway, C. A. Systemic lupus erythematosus. Description of 37 cases in children and a discussion of endocrine therapy in 32 of the cases. Pediatrics 26, 570–585 (1960).

    CAS  PubMed  Google Scholar 

  4. van Vollenhoven, R. F. et al. Treat-to-target in systemic lupus erythematosus: recommendations from an international task force. Ann. Rheum. Dis. 73, 958–967 (2014).

    Article  Google Scholar 

  5. 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 

  6. 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 

  7. 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 

  8. Bernatsky, S. et al. Mortality in systemic lupus erythematosus. Arthritis Rheum. 54, 2550–2557 (2006).

    Article  CAS  Google Scholar 

  9. Mok, C. C., To, C. H., Ho, L. Y. & Yu, K. L. Incidence and mortality of systemic lupus erythematosus in a southern Chinese population, 2000–2006. J. Rheumatol. 35, 1978–1982 (2008).

    Google Scholar 

  10. Urowitz, M. B., Gladman, D. D., Tom, B. D., Ibañez, D. & Farewell, V. T. Changing patterns in mortality and disease outcomes for patients with systemic lupus erythematosus. J. Rheumatol. 35, 2152–2158 (2008).

    Article  Google Scholar 

  11. Manzi, S. et al. Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study. Am. J. Epidemiol. 145, 408–415 (1997).

    Article  CAS  Google Scholar 

  12. Nived, O., Jönsen, A., Bengtsson, A. A., Bengtsson, C. & Sturfelt, G. High predictive value of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for survival in systemic lupus erythematosus. J. Rheumatol. 29, 1398–1400 (2002).

    PubMed  Google Scholar 

  13. Nossent, J. et al. Disease activity and damage accrual during the early disease course in a multinational inception cohort of patients with systemic lupus erythematosus. Lupus 19, 949–956 (2010).

    Article  CAS  Google Scholar 

  14. Uribe, A. G., McGwin, G., Jr, Reveille, J. D. & Alarcón, G. S. What have we learned from a 10-year experience with the LUMINA (Lupus in Minorities; Nature vs. nurture) cohort? Where are we heading? Autoimmun. Rev. 3, 321–329 (2004).

    Article  Google Scholar 

  15. Alarcón, G. S. et al. Systemic lupus erythematosus in three ethnic groups. XX. Damage as a predictor of further damage. Rheumatology (Oxford) 43, 202–205 (2004).

    Article  Google Scholar 

  16. Da Silva, J. A. Safety of low dose glucocorticoid treatment in rheumatoid arthritis: published evidence and prospective trial data. Ann. Rheum. Dis. 65, 285–293 (2006).

    Article  CAS  Google Scholar 

  17. Ibañez, D., Gladman, D. D. & Urowitz, M. B. Adjusted mean Systemic Lupus Erythematosus Disease Activity Index-2K is a predictor of outcome in SLE. J. Rheumatol. 32, 824–827 (2005).

    PubMed  Google Scholar 

  18. Nikpour, M., Urowitz, M. B., Ibañez, D., Harvey, P. J. & Gladman, D. D. Importance of cumulative exposure to elevated cholesterol and blood pressure in development of atherosclerotic coronary artery disease in systemic lupus erythematosus: a prospective proofofconcept cohort study. Arthritis Res. Ther. 13, R156 (2011).

    Article  Google Scholar 

  19. Golder, V., Connelly, K., Staples, M., Morand, E. & Hoi, A. Association of Asian ethnicity with disease activity in SLE: an observational study from the Monash Lupus Clinic. Lupus 22, 1425–1430 (2013).

    Article  CAS  Google Scholar 

  20. Turchetti, G., Yazdany, J., Palla, I., Yelin, E. & Mosca, M. Systemic lupus erythematosus and the economic perspective: a systematic literature review and points to consider. Clin. Exp. Rheumatol. 30 (4 Suppl. 73) S116–S122 (2012).

    PubMed  PubMed Central  Google Scholar 

  21. Sutcliffe, N., Clarke, A. E., Taylor, R., Frost, C. & Isenberg, D. A. Total costs and predictors of costs in patients with systemic lupus erythematosus. Rheumatology (Oxford) 40, 37–47 (2001).

    Article  CAS  Google Scholar 

  22. Gladman, D. et al. The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum. 39, 363–369 (1996).

    Article  CAS  Google Scholar 

  23. Bombardier, C., Gladman, D. D., Urowitz, M. B., Caron, D. & Chang, C. H. Derivation of the SLEDAI. A disease activity index for lupus patients. The committee on prognosis studies in SLE. Arthritis Rheum. 35, 630–640 (1992).

    Article  CAS  Google Scholar 

  24. Strand, V. Clinical trial design in systemic lupus erythematosus: lessons learned and future directions. Lupus 13, 406–411 (2004).

    Article  CAS  Google Scholar 

  25. Yee, C.S. et al. Revised British Isles Lupus Assessment Group 2004 index: a reliable tool for assessment of systemic lupus erythematosus activity. Arthritis Rheum. 54, 3300–3305 (2006).

    Article  Google Scholar 

  26. Neville, C. et al. Learning from discordance in patient and physician global assessments of systemic lupus erythematosus disease activity. J. Rheumatol. 27, 675–679 (2000).

    CAS  PubMed  Google Scholar 

  27. Yen, J. C. et al. Determinants of discordance between patients and physicians in their assessment of lupus disease activity. J. Rheumatol. 30, 1967–1976 (2003).

    PubMed  Google Scholar 

  28. Wallace, D. J. et al. A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus. Arthritis Rheum. 61, 1168–1178 (2009).

    Article  CAS  Google Scholar 

  29. Wallace, D. J. et al. Efficacy and safety of epratuzumab in patients with moderate/severe active systemic lupus erythematosus: results from EMBLEM, a phase IIb, randomised, double-blind, placebo-controlled, multicentre study. Ann. Rheum. Dis. 73, 183–190 (2013).

    Article  Google Scholar 

  30. Urowitz, M. B., Feletar, M., Bruce, I. N., Ibañez, D. & Gladman, D. D. Prolonged remission in systemic lupus erythematosus. J. Rheumatol. 32, 1467–1472 (2005).

    PubMed  Google Scholar 

  31. Steiman, A. J., Gladman, D. D., Ibañez, D. & Urowitz, M. B. Prolonged serologically active clinically quiescent systemic lupus erythematosus: frequency and outcome. J. Rheumatol. 37, 1822–1827 (2010).

    Article  Google Scholar 

  32. Steiman, A. J., Gladman, D. D., Ibañez, D. & Urowitz, M. B. Outcomes in patients with systemic lupus erythematosus with and without a prolonged serologically active clinically quiescent period. Arthritis Care Res. 64, 511–518 (2012).

    Article  Google Scholar 

  33. Khanna, D. et al. Evaluation of the preliminary definitions of minimal disease activity and remission in an early seropositive rheumatoid arthritis cohort. Arthritis Rheum. 57, 440–447 (2007).

    Article  Google Scholar 

  34. Rullo, O. J. & Tsao, B. P. Recent insights into the genetic basis of systemic lupus erythematosus. Ann. Rheum. Dis. 72 (Suppl. 2), ii56–ii61 (2013).

    Article  CAS  Google Scholar 

  35. Alarcón, G. S. et al. Systemic lupus erythematosus in three ethnic groups. VII [correction of VIII]. Predictors of early mortality in the LUMINA cohort. LUMINA Study Group. Arthritis Rheum. 45, 191–202 (2001).

    Article  Google Scholar 

  36. Walsh, S. J. & DeChello, L. M. Geographical variation in mortality from systemic lupus erythematosus in the United States. Lupus 10, 637–646 (2001).

    Article  CAS  Google Scholar 

  37. Bossingham, D. Systemic lupus erythematosus in the far north of Queensland. Lupus 12, 327–331 (2003).

    Article  CAS  Google Scholar 

  38. Gladman, D. D., Ibañez, D. & Urowitz, M. B. Systemic lupus erythematosus disease activity index 2000. J. Rheumatol. 29, 288–291 (2002).

    Google Scholar 

  39. van der Heijde, D. M., van 't Hof, M., van Riel, P. L. & van de Putte, L. B. Development of a disease activity score based on judgment in clinical practice by rheumatologists. J. Rheumatol. 20, 579–581 (1993).

    CAS  PubMed  Google Scholar 

  40. Felson, D. T. et al. American College of Rheumatology/European League Against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Arthritis Rheum. 63, 573–586 (2011).

    Article  Google Scholar 

Download references

Acknowledgements

E.F.M. receives funding support from Arthritis Victoria and the National Health and Medical Research Council, Australia. M.N. receives funding support from the National Health and Medical Research Council, Australia. K.F. receives funding support from Arthritis Australia.

Author information

Authors and Affiliations

  1. Monash University School of Clinical Sciences, Monash Medical Centre, 246 Clayton Road, Clayton, Melbourne, 3168, VIC, Australia

    Kate Franklyn, Alberta Hoi & Eric F. Morand

  2. Departments of Medicine and Rheumatology, The University of Melbourne at St Vincent's Hospital Melbourne, 41 Victoria Parade, Fitzroy, Melbourne, 3065, VIC, Australia

    Mandana Nikpour

Authors
  1. Kate Franklyn
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alberta Hoi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mandana Nikpour
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eric F. Morand
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

K.F. researched the data for the article and wrote the manuscript. A.H, M.N. and E.F.M provided a substantial contribution to discussions of the content, and to review and/or editing of the manuscript before submission. M.N. and E.F.M. contributed equally.

Corresponding author

Correspondence to Eric F. Morand.

Ethics declarations

Competing interests

E.F.M. declares that he has received an unrestricted educational grant from GSK. The other authors declare no competing interests.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Franklyn, K., Hoi, A., Nikpour, M. et al. The need to define treatment goals for systemic lupus erythematosus. Nat Rev Rheumatol 10, 567–571 (2014). https://doi.org/10.1038/nrrheum.2014.118

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrrheum.2014.118

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