Dose reduction of glucocorticoids in systemic lupus erythematosus

Glucocorticoids are a mainstay of treatment for systemic lupus erythematosus (SLE). But due to long-term adverse effects, dose reduction is becoming a crucial part of treat-to-target management goals. However, data regarding the optimum dose target are conflicting. Recommendations from EULAR - The European Alliance of Associations for Rheumatology - advise a glucocorticoid dose of no more than 5 mg/day. However, the threshold in the validated lupus low disease activity state (LLDAS) definition is no more than 7.5 mg/day. It is also still unclear whether it is safe and feasible to withdraw glucocorticoids after achieving remission.

In a session on diagnosing and managing complex diseases at the 2024 EULAR congress in Vienna, two abstracts tackled this issue.

First, Filippo Vesentini presented on the risk of flare with glucocorticoid compared to low-dose maintenance - based on a retrospective analysis of prospectively collected data from people with SLE. Flare-free remission and predictors of such were evaluated respectively in remitted patients on and off glucocorticoids.

During follow-up, 484 patients achieved remission at least once during follow-up - 360 patients of these discontinued glucocorticoids, while 124 remained on a dose of 5 mg per day or less. There were subsequently 85 flares over a mean period of 87 months. Of these, 48 were in those who had discontinued glucocorticoids, and 37 in those remaining on a low dose - equivalent to an annual flare rate of 8.5 and 1.65 flares per 100 patients/year respectively. Disease duration and anti-U1RNP were positive and negative predictors of flare-free remission, respectively. The group conclude that glucocorticoid discontinuation after proper tapering is safe and associated with a low risk of flare.

A second presentation from Eric Morand explored whether lowering the glucocorticoid ceiling in the definition of LLDAS - to be in line with the 5 mg EULAR recommendations - (LLDAS-5) was associated with improved protection from flare, irreversible organ damage accrual, and mortality when compared with the original 7.5 mg definition (LLDAS-7.5).

Data were analysed from a longitudinal SLE cohort of 2,213 patients. Of these, 2.1% died, 29% accrued organ damage, and 67% experienced flares. LLDAS-7.5 was achieved by 87% of patients in 47% of visits, whereas 83% of patients attained LLDAS-5 in 42% of visits, with considerable and predicted overlap. The magnitude of protection provided by LLDAS attainment against mortality, irreversible organ damage accrual, or flare was similar with both glucocorticoid dose thresholds.

These findings support the idea that while lowering glucocorticoid dose remains a key goal of management for people with SLE, there was no evidence to support revising the dose threshold of the LLDAS definition, and therefore the validated definition should continue to be used in both clinical studies and everyday patient care.

Source:
Journal references:
  • Vesentini, F., et al. (2024). Glucocorticoid withdrawal does not increase the risk of flares during remission in Systemic Lupus Erythematosus. Ann Rheum Dis. DOI: 10.1136/annrheumdis-2024-eular.5032.
  • Kandane-Rathnayake, R., et al. (2024) Impact of glucocorticoid dose threshold in definition of Lupus Low Disease Activity State. Ann Rheum Dis. DOI: 10.1136/annrheumdis-2024-eular.2742.

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