Remission and low disease activity (LDA) are the most important targets to achieve in systemic lupus erythematosus (SLE) management.^1–4 Belimumab is the only biologic drug approved for SLE and whether or not it can help lupus patients to achieve these targets is a critical question.

In a post-hoc analysis carried out in patients enrolled in BLISS-52 and BLISS-76, remission and LDA were able to discriminate response to belimumab 10 mg/kg from placebo.^{5 6} Notably, clinical (c) SLEDAI-2K=0 was the best discriminator⁶ and, importantly, in a recent multicentre cohort study including 646 patients, cSLEDAI=0 had the best performance in predicting damage accrual compared with all other definitions of remission.⁷

In real-life the proportion of patients who can achieve a stable low lupus disease activity state (LLDAS) and remission was higher than that obtained in randomised controlled trials, as shown in two recent studies.^{8 9}

A recent Italian multicentre cohort study of 466 patients on the use of belimumab in clinical practice settings, with a median follow-up of 18 months (range 1–60 months), showed that 71.7% of patients achieved LDA, 61.3% SRI-4, and 41.1% remission at 12 months, with these figures being maintained over time.¹⁰ The most important independent predictors of SRI-4 response were baseline SLEDAI2K≥10, SLE duration ≤2 years and a baseline SLICC damage index=0. Independent predictors of remission and LDA were baseline SLEDAI-2K <10, baseline SLICC damage index=0 and prednisone intake ≤7.5 mg, and negative predictors of remission and LDA were number of flares in the 3 years before belimumab treatment initiation and baseline renal involvement. Notably, patients spending at least 50% of follow-up in LDA (66%) or at least 25% of follow-up in remission (42.9%) accumulated less damage at the end of the follow-up.

Consequently, this study provided novel evidence that an earlier use of belimumab in patients with active SLE and low damage may maximise its efficacy in clinical practice.

Learning Objectives

• Explain the importance of achieving remission or LDA in SLE management

• Describe the role of belimumab in achieving remission or LDA in post-hoc analysis of the randomised control trials

• Discuss the best use of belimumab in clinical practice settings

References

1. Gatto M, Zen M, Iaccarino L, et al. New therapeutic strategies in systemic lupus erythematosus management. Nat Rev Rheumatol 2019;15(1):30–48.

2. Zen M, Iaccarino L, Gatto M, et al. Prolonged remission in Caucasian patients with SLE: prevalence and outcomes. Ann Rheum Dis 2015;74(12):2117–22.

3. Zen M, Iaccarino L, Gatto M, 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):562–65.

4. Zen M, Iaccarino L, Gatto M, et al. Lupus low disease activity state is associated with a decrease in damage progression in Caucasian patients with SLE, but overlaps with remission. Ann Rheum Dis 2018;77(1):104–10.

5. Oon S, Huq M, Golder V, et al. 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):629–33.

6. Parodis I, Emamikia S, Gomez A, et al. Clinical SLEDAI-2K zero may be a pragmatic outcome measure in SLE studies. Expert opinion on biological therapy 2019;19(2):157–68.

7. Saccon F, Zen M, Gatto M, et al. Remission in systemic lupus erythematosus: testing different definitions in a large multicentre cohort. Ann Rheum Dis 2020;79(7):943–50.

8. Fanouriakis A, Adamichou C, Koutsoviti S, et al. Low disease activity-irrespective of serologic status at baseline-associated with reduction of corticosteroid dose and number of flares in patients with systemic lupus erythematosus treated with belimumab: A real-life observational study. Semin Arthritis Rheum 2018;48(3):467–74.

9. Sbeih N, Mathian A, Pineton de Chambrun M, et al. Achieving lupus low-disease activity and remission states under belimumab in refractory systemic lupus erythematosus: time and organ involvement matter. Ann Rheum Dis 2019:annrheumdis-2019-215732.

10. Gatto M, Saccon F, Zen M, et al. Early disease and low baseline damage predict response to belimumab in patients with systemic lupus erythematosus. Arthritis Rheumatol 2020 doi: 10.1002/art.41253 [published Online First: 2020/04/11]