Treat-to-target SLE strategy in 10 years: Discussion of current limitations and available options for implementation in real-world clinical practice
https://doi.org/10.47360/1995-4484-2025-229-238
Abstract
In January 2013, at the initiative of the world’s leading rheumatologists Ronald F. van Vollenhoven, Josef Smolen, Marta Mosca and Matthias Schneider, a project was launched to create the “Treat-to-Target” concept for systemic lupus erythematosus (SLE). In 2014, the group published recommendations “Treat-to-Target for SLE”. The article discusses the problems of implementing the strategy in real clinical practice and discusses the proposed ways of its implementation, proposed by international experts in 2025: 5 basic principles and 11 statements.
About the Authors
E. A. AseevaRussian Federation
Elena A. Aseeva.
115522, Moscow, Kashirskoye Highway, 34A
Competing Interests:
None
S. K. Solovyev
Russian Federation
Sergey K. Solovyev.
115522, Moscow, Kashirskoye Highway, 34A
Competing Interests:
None
E. A. Pletnev
Russian Federation
Evgenii A. Pletnev.
115522, Moscow, Kashirskoye Highway, 34A
Competing Interests:
None
G. M. Koilubaeva
Kyrgyzstan
Gulazik M. Koilubaeva.
720040, Bishkek, Togoloka Moldo str., 3
Competing Interests:
None
B. G. Issayeva
Kazakhstan
Bakytsholpan G. Issayeva.
050012, Almaty, Tole bi str., 94
Competing Interests:
None
E. L. Nasonov
Russian Federation
Evgeny L. Nasonov.
115522, Moscow, Kashirskoye Highway, 34A
Competing Interests:
None
References
1. Nasonov EL, Soloviev SK, Arshinov AV. Systemic lupus erythematosus: History and modernity. Nauchno-Prakticheskaya Revmatologia = Rheumatology Science and Practice. 2022;60(4):397-412 (In Russ.). doi: 10.47360/1995-4484-2022-397-412
2. van Vollenhoven RF, Mosca M, Bertsias G, Isenberg D, Kuhn A, Lerstrøm K, et al. Treat-to-target in systemic lupus erythematosus: Recommendations from an international task force. Ann Rheum Dis. 2014;73(6):958-967. doi: 10.1136/annrheumdis-2013-205139
3. Soloviev SK, Aseeva EA, Popkova TV, Klyukvina NG, Reshetnyak TM, Lisitsyna TA, et al. Treat-to-target SLE recommendations from the international task force and Russian experts’ commentaries. Nauchno-Prakticheskaya Revmatologia = Rheumatology Science and Practice. 2015;53(1):9-16 (In Russ.). doi: 10.14412/1995-4484-2015-9-16
4. Fanouriakis A, Kostopoulou M, Alunno A, Aringer M, Bajema I, Boletis JN, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis. 2019;78(6):736-745. doi: 10.1136/annrheumdis-2019-215089
5. Fanouriakis A, Kostopoulou M, Andersen J, Aringer M, Arnaud L, Bae SC, et al. EULAR recommendations for the management of systemic lupus erythematosus: 2023 update. Ann Rheum Dis. 2024;83(1):15-29. doi: 10.1136/ard-2023-224762
6. Franklyn K, Hoi A, Nikpour M, Morand EF. The need to define treatment goals for systemic lupus erythematosus. Nat Rev Rheumatol. 2014;10(9):567-571. doi: 10.1038/nrrheum.2014.118
7. Franklyn K, Lau CS, Navarra SV, Louthrenoo W, Lateef A, Hamijoyo L, et al.; Asia-Pacific Lupus Collaboration. Definition and initial validation of a Lupus Low Disease Activity State (LLDAS). Ann Rheum Dis. 2016;75(9):1615-1621. doi: 10.1136/annrheumdis-2015-207726
8. Gladman DD, Ibañez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. J Rheumatol. 2002;29(2):288-291.
9. Urowitz MB, Feletar M, Bruce IN, Ibañez D, Gladman DD. Prolonged remission in systemic lupus erythematosus. J Rheumatol. 2005;32(8):1467-1472.
10. van Vollenhoven RF, Bertsias G, Doria A, Isenberg D, Morand E, Petri MA, et al. 2021 DORIS definition of remission in SLE: Final recommendations from an international task force. Lupus Sci Med. 2021;8(1):e000538. doi: 10.1136/lupus-2021-000538
11. Zucchi D, Cardelli C, Elefante E, Tani C, Mosca M. Treat-to-target in systemic lupus erythematosus: Reality or pipe dream. J Clin Med. 2023;12(9):3348. doi: 10.3390/jcm12093348
12. Zonana-Nacach A, Barr SG, Magder LS, Petri M. Damage in systemic lupus erythematosus and its association with corticosteroids. Arthritis Rheum. 2000;43:1801-1808.
13. Gladman DD, Urowitz MB, Rahman P, Ibañez D, Tam LS. Accrual of organ damage over time in patients with systemic lupus erythematosus. J Rheumatol. 2003;30(9):1955-1959.
14. Magder LS, Petri M. Incidence of and risk factors for adverse cardiovascular events among patients with systemic lupus erythematosus. Am J Epidemiol. 2012;176:708-719. doi: 10.1093/aje/kws130
15. Ruiz-Irastorza G, Olivares N, Ruiz-Arruza I, Martinez-Berriotxoa A, Egurbide MV, Aguirre C. Predictors of major infections in systemic lupus erythematosus. Arthritis Res Ther. 2009;11(4):R109. doi: 10.1186/ar2764
16. Murimi-Worstell IB, Lin DH, Nab H, Kan HJ, Onasanya O, Tierce JC, et al. Association between organ damage and mortality in systemic lupus erythematosus: A systematic review and meta-analysis. BMJ Open. 2020;10(5):e031850. doi: 10.1136/bmjo-pen-2019-031850
17. Zahr ZA, Fang H, Magder LS, Petri M. Predictors of corticosteroid tapering in SLE patients: The Hopkins Lupus Cohort. Lupus. 2013;22(7):697-701. doi: 10.1177/0961203313490434
18. Mathian A, Pha M, Haroche J, Cohen-Aubart F, Hié M, Pineton de Chambrun M, et al. Withdrawal of low-dose prednisone in SLE patients with a clinically quiescent disease for more than 1 year: A randomised clinical trial. Ann Rheum Dis. 2020;79(3):339-346. doi: 10.1136/annrheumdis-2019-216303
19. Tselios K, Gladman DD, Su J, Urowitz MB. Gradual glucocorticosteroid withdrawal is safe in clinically quiescent systemic lupus erythematosus. ACR Open Rheumatol. 2021;3(8):550-557. doi: 10.1002/acr2.11267
20. Tani C, Elefante E, Signorini V, Zucchi D, Lorenzoni V, Carli L, et al. Glucocorticoid withdrawal in systemic lupus erythematosus: Are remission and low disease activity reliable starting points for stopping treatment? A real-life experience. RMD Open. 2019;5(2):e000916. doi: 10.1136/rmdopen-2019-000916
21. Nakai T, Fukui S, Ikeda Y, Suda M, Tamaki H, Okada M. Glucocorticoid discontinuation in patients with SLE with prior severe organ involvement: A single-center retrospective analysis. Lupus Sci Med. 2022;9(1):e000682. doi: 10.1136/lupus-2022-000682
22. Goswami RP, Sit H, Ghosh P, Sircar G, Ghosh A. Steroid-free remission in lupus: Myth or reality; an observational study from a tertiary referral centre. Clin Rheumatol. 2019;38(4):1089-1097. doi: 10.1007/s10067-018-4377-7
23. Piga M, Parodis I, Touma Z, Legge A, Ugarte-Gil MF, Hmamouchi I, et al. Framework for implementing treat-to-target in systemic lupus erythematosus routine clinical care: Consensus statements from an international task force. Autoimmun Rev. 2025;24(5):103773. doi: 10.1016/j.autrev.2025.103773
24. Piga M, Floris A, Sebastiani GD, Prevete I, Iannone F, Coladonato L, et al. Risk factors of damage in early diagnosed systemic lupus erythematosus: Results of the Italian multicentre Early Lupus Project inception cohort. Rheumatology (Oxford). 2020;59(9):2272-2281. doi: 10.1093/rheumatology/kez584
25. Piga M, Floris A, Cappellazzo G, Chessa E, Congia M, Mathieu A, et al. Failure to achieve lupus low disease activity state (LLDAS) six months after diagnosis is associated with early damage accrual in Caucasian patients with systemic lupus erythematosus. Arthritis Res Ther. 2017;19(1):247. doi: 10.1186/s13075-017-1451-5
26. Zen M, Gatto M, Doria A. Defining the targets in SLE management: Insights and unmet gaps. Ann Rheum Dis. 2022;81(11):1483-1485. doi: 10.1136/ard-2022-222991
27. Mendoza-Pinto C, Etchegaray-Morales I, Ugarte-Gil MF. Improving access to SLE therapies in low and middle-income countries. Rheumatology (Oxford). 2023;62(Suppl 1):30-35. doi: 10.1093/rheumatology/keac530
28. Charles C, Gafni A, Whelan T. Shared decision-making in the medical encounter: What does it mean? (or it takes at least two to tango). Soc Sci Med. 1997;44(5):681-692. doi: 10.1016/s0277-9536(96)00221-3
29. Cai T, Zhao J, Yang Y, Jiang Y, Zhang JA. Hydroxychloroquine use reduces mortality risk in systemic lupus erythematosus: A systematic review and meta-analysis of cohort studies. Lupus. 2022;31(14):1714-1725. doi: 10.1177/09612033221129774
30. Pagès-Puigdemont N, Mangues MA, Masip M, Gabriele G, Fernández-Maldonado L, Blancafort S, et al. Patients’ perspective of medication adherence in chronic conditions: A qualitative study. Adv Ther. 2016;33(10):1740-1754. doi: 10.1007/s12325-016-0394-6
31. Parodis I, Girard-Guyonvarc’h C, Arnaud L, Distler O, Domján A, Van den Ende CHM, et al. EULAR recommendations for the non-pharmacological management of systemic lupus erythematosus and systemic sclerosis. Ann Rheum Dis. 2024;83(6):720-729. doi: 10.1136/ard-2023-224416
32. So H, Szeto CC, Tam LS. Patient acceptance of using telemedicine for follow-up of lupus nephritis in the COVID-19 outbreak. Ann Rheum Dis. 2021;80(6):e97. doi: 10.1136/annrheumdis-2020-218220
33. Au Eong JTW, Lateef A, Liang S, Lim SHH, Tay SH, Mak A, et al. Impact of teleconsultation on subsequent disease activity and flares in patients with systemic lupus erythematosus. Rheumatology (Oxford). 2022;61(5):1911-1918. doi: 10.1093/rheumatology/keab694
34. Pons-Estel BA, Bonfa E, Soriano ER, Cardiel MH, Izcovich A, Popoff F, et al.; Grupo Latino Americano de Estudio del Lupus (GLADEL) and Pan-American League of Associations of Rheumatology (PANLAR). First Latin American clinical practice guidelines for the treatment of systemic lupus erythematosus: Latin American Group for the Study of Lupus (GLADEL, Grupo Latino Americano de Estudio del Lupus)-Pan-American League of Associations of Rheumatology (PANLAR). Ann Rheum Dis. 2018;77(11):1549-1557. doi: 10.1136/annrheumdis-2018-213512
35. Kandane-Rathnayake R, Golder V, Louthrenoo W, Chen YH, Cho J, Lateef A, et al.; Asia-Pacific Lupus Collaboration. Lupus low disease activity state and remission and risk of mortality in patients with systemic lupus erythematosus: A prospective, multinational, longitudinal cohort study. Lancet Rheumatol. 2022;4(12):e822-e830. doi: 10.1016/S2665-9913(22)00304-6
36. Golder V, Kandane-Rathnayake R, Huq M, Nim HT, Louthrenoo W, Luo SF, et al. Lupus low disease activity state as a treatment endpoint for systemic lupus erythematosus: A prospective validation study. Lancet Rheumatol. 2019;1(2):e95-e102. doi: 10.1016/S2665-9913(19)30037-2
37. Zen M, Iaccarino L, Gatto M, Bettio S, Nalotto L, Ghirardello A, et al. Prolonged remission in Caucasian patients with SLE: Prevalence and outcomes. Ann Rheum Dis. 2015;74(12):2117-2122. doi: 10.1136/annrheumdis-2015-207347
38. Yang Z, Cheng C, Wang Z, Wang Y, Zhao J, Wang Q, et al. Prevalence, predictors, and prognostic benefits of remission achievement in patients with systemic lupus erythematosus: A systematic review. Arthritis Care Res (Hoboken). 2022;74(2):208-218. doi: 10.1002/acr.24464
39. Floris A, Piga M, Perra D, Chessa E, Congia M, Mathieu A, et al. Treatment target in newly diagnosed systemic lupus erythematosus: The association of lupus low disease activity state and remission with lower accrual of early damage. Arthritis Care Res (Hoboken). 2020;72(12):1794-1799. doi: 10.1002/acr.24086
40. Moroni G, Gatto M, Tamborini F, Quaglini S, Radice F, Saccon F, et al. Lack of EULAR/ERA-EDTA response at 1 year predicts poor long-term renal outcome in patients with lupus nephritis. Ann Rheum Dis. 2020;79(8):1077-1083. doi: 10.1136/annrheumdis-2020-216965
41. Gatto M, Frontini G, Calatroni M, Reggiani F, Depascale R, Cruciani C, et al. Effect of sustained clinical remission on the risk of lupus flares and impaired kidney function in patients with lupus nephritis. Kidney Int Rep. 2024;9(4):1047-1056. doi: 10.1016/j.ekir.2024.01.016
42. Chambers SA, Rahman A, Isenberg DA. Treatment adherence and clinical outcome in systemic lupus erythematosus. Rheumatology (Oxford). 2007;46:895-898.
43. Nguyen Y, Blanchet B, Urowitz MB, Hanly JG, Gordon C, Bae SC, et al. Association between severe nonadherence to hydroxychloroquine and systemic lupus erythematosus flares, damage, and mortality in 660 patients from the SLICC inception cohort. Arthritis Rheumatol. 2023;75(12):2195-2206. doi: 10.1002/art.42645
44. Dall’Era M, Stone D, Levesque V, Cisternas M, Wofsy D. Identification of biomarkers that predict response to treatment of lupus nephritis with mycophenolate mofetil or pulse cyclophosphamide. Arthritis Care Res (Hoboken). 2011;63(3):351-357. doi: 10.1002/acr.20397
45. Tamirou F, Lauwerys BR, Dall’Era M, Mackay M, Rovin B, Cervera R, et al.; MAINTAIN Nephritis Trial Investigators. A proteinuria cut-off level of 0.7 g/day after 12 months of treatment best predicts long-term renal outcome in lupus nephritis: Data from the MAINTAIN Nephritis Trial. Lupus Sci Med. 2015;2(1):e000123. doi: 10.1136/lupus-2015-000123
46. Parodis I, Adamichou C, Aydin S, Gomez A, Demoulin N, Weinmann-Menke J, et al. Per-protocol repeat kidney biopsy portends relapse and long-term outcome in incident cases of proliferative lupus nephritis. Rheumatology (Oxford). 2020;59(11):3424-3434. doi: 10.1093/rheumatology/keaa129
47. Cruciani C, Zen M, Gatto M, Morand E, Doria A. Assessment of disease activity and damage in SLE: Are we there yet? Best Pract Res Clin Rheumatol. 2023;37(4):101896. doi: 10.1016/j.berh.2023.101896
48. Zen M, Iaccarino L, Gatto M, Bettio S, Saccon F, Ghirardello A, et al. The effect of different durations of remission on damage accrual: Results from a prospective monocentric cohort of Caucasian patients. Ann Rheum Dis. 2017;76(3):562-565. doi: 10.1136/annrheumdis-2016-210154
49. Zen M, Salmaso L, Barbiellini Amidei C, Fedeli U, Bellio S, Iaccarino L, et al. Mortality and causes of death in systemic lupus erythematosus over the last decade: Data from a large population-based study. Eur J Intern Med. 2023;112:45-51. doi: 10.1016/j.ejim.2023.02.004
50. Ugarte-Gil MF, Mendoza-Pinto C, Reátegui-Sokolova C, Pons-Estel GJ, van Vollenhoven RF, Bertsias G, et al. Achieving remission or low disease activity is associated with better outcomes in patients with systemic lupus erythematosus: A systematic literature review. Lupus Sci Med. 2021;8(1):e000542. doi: 10.1136/lupus-2021-000542
51. Fanouriakis A, Kostopoulou M, Cheema K, Anders HJ, Aringer M, Bajema I, et al. 2019 update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis. Ann Rheum Dis. 2020;79(6):713-723. doi: 10.1136/annrheumdis-2020-216924
52. Kidney Disease: Improving Global Outcomes (KDIGO) Lupus Nephritis Work Group. KDIGO 2024 clinical practice guideline for the management of lupus nephritis. Kidney Int. 2024;105(1S):1-69. doi: 10.1016/j.kint.2023.09.002
53. Sammaritano LR, Askanase A, Bermas BL, Dall’Era M, Duarte-García A, Hiraki LT, et al. 2024 American College of Rheumatology (ACR) guideline for the screening, treatment, and management of lupus nephritis. Arthritis Care Res (Hoboken). 2025 Mar 24. doi: 10.1002/acr.25528
54. Floris A, Chessa E, Sebastiani GD, Prevete I, Iannone F, Coladonato L, et al.; Study Group on Early SLE of the Italian Society of Rheumatology (SIR). Glucocorticoid tapering and associated outcome in patients with newly diagnosed systemic lupus erythematosus: The real-world GULP prospective observational study. RMD Open. 2022;8(2):e002701. doi: 10.1136/rmdopen-2022-002701
55. Mathian A, Arnaud L, Ruiz-Irastorza G. Is it safe to withdraw low-dose glucocorticoids in SLE patients in remission? Autoimmun Rev. 2024;23(1):103446. doi: 10.1016/j.autrev.2023.103446
56. Palmowski A, Pankow A, Terziyska K, Nielsen SM, Christensen R, Bliddal H, et al. Continuing versus tapering low-dose glucocorticoids in patients with rheumatoid arthritis and systemic lupus erythematosus in states of low disease activity or remission: A systematic review and meta-analysis of randomised trials. Semin Arthritis Rheum. 2024;64:152349. doi: 10.1016/j.semarthrit.2023.152349
57. Tselios K, Gladman DD, Su J, Urowitz MB. Gradual glucocorticosteroid withdrawal is safe in clinically quiescent systemic lupus erythematosus. ACR Open Rheumatol. 2021;3(8):550-557. doi: 10.1002/acr2.11267
58. Oiwa H, Suga T, Hosokawa Y, Araki K. Glucocorticoid-free remission in patients with SLE in the era of biologics: Immune complex disease is likely to benefit from current medications. Lupus. 2024;33(5):502-510. doi: 10.1177/09612033241238055
59. Fasano S, Coscia MA, Pierro L, Ciccia F. Which patients with systemic lupus erythematosus in remission can withdraw low dose steroids? Results from a single inception cohort study. Lupus. 2021;30(6):991-997. doi: 10.1177/09612033211002269
60. Katsumata Y, Inoue E, Harigai M, Cho J, Louthrenoo W, Hoi A, et al.; Asia-Pacific Lupus Collaboration. Risk of flare and damage accrual after tapering glucocorticoids in modified serologically active clinically quiescent patients with systemic lupus erythematosus: A multinational observational cohort study. Ann Rheum Dis. 2024;83(8):998-1005. doi: 10.1136/ard-2023-225369
61. Ji L, Gao D, Hao Y, Huang H, Wang Y, Deng X, et al. Low-dose glucocorticoids withdrawn in systemic lupus erythematosus: A desirable and attainable goal. Rheumatology (Oxford). 2022;62(1):181-189. doi: 10.1093/rheumatology/keac225
62. Ordi-Ros J, Sáez-Comet L, Pérez-Conesa M, Vidal X, Mitjavila F, Castro Salomó A, et al. Enteric-coated mycophenolate sodium versus azathioprine in patients with active systemic lupus erythematosus: A randomised clinical trial. Ann Rheum Dis. 2017;76(9):1575-1582. doi: 10.1136/annrheumdis-2016-210882
63. Oon S, Huq M, Golder V, Ong PX, Morand EF, Nikpour M. Lupus low disease activity state (LLDAS) discriminates responders in the BLISS-52 and BLISS-76 phase III trials of belimumab in systemic lupus erythematosus. Ann Rheum Dis. 2019;78(5):629-633. doi: 10.1136/annrheumdis-2018-214427
64. Zen M, Saccon F, Gatto M, Montesso G, Larosa M, Benvenuti F, et al. Prevalence and predictors of flare after immunosuppressant discontinuation in patients with systemic lupus erythematosus in remission. Rheumatology (Oxford). 2020;59(7):1591-1598. doi: 10.1093/rheumatology/kez422
65. Zen M, Fuzzi E, Loredo Martinez M, Depascale R, Fredi M, Gatto M, et al. Immunosuppressive therapy withdrawal after remission achievement in patients with lupus nephritis. Rheumatology (Oxford). 2022;61(2):688-695. doi: 10.1093/rheumatology/keab373
66. Floris A, Piga M, Cauli A, Mathieu A. Predictors of flares in systemic lupus erythematosus: Preventive therapeutic intervention based on serial anti-dsDNA antibodies assessment. Analysis of a monocentric cohort and literature review. Autoimmun Rev. 2016;15(7):656-663. doi: 10.1016/j.autrev.2016.02.019
67. Kostopoulou M, Ugarte-Gil MF, Pons-Estel B, van Vollenhoven RF, Bertsias G. The association between lupus serology and disease outcomes: A systematic literature review to inform the treat-to-target approach in systemic lupus erythematosus. Lupus. 2022;31(3):307-318. doi: 10.1177/09612033221074580
68. Yeo AL, Kandane-Rathnayake R, Koelmeyer R, Golder V, Louthrenoo W, Chen YH, et al.; Asia Pacific Lupus Collaboration. SMART-SLE: Serology monitoring and repeat testing in systemic lupus erythematosus – An analysis of anti-double-stranded DNA monitoring. Rheumatology (Oxford). 2024;63(2):525-533. doi: 10.1093/rheumatology/kead231
Review
For citations:
Aseeva E.A., Solovyev S.K., Pletnev E.A., Koilubaeva G.M., Issayeva B.G., Nasonov E.L. Treat-to-target SLE strategy in 10 years: Discussion of current limitations and available options for implementation in real-world clinical practice. Rheumatology Science and Practice. 2025;63(3):229-238. (In Russ.) https://doi.org/10.47360/1995-4484-2025-229-238