Gradual withdrawal of steroids safe in systemic lupus erythematosus

21st July 2021

Gradual reduction of glucocorticoids in patients with quiescent systemic lupus erythematosus does not increase flares or damage accrual.

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects the joints, skin, brain, lungs and kidney, leading to widespread inflammation and tissue damage. Treatment involves the use of hydroxychloroquine and according to guidance issued by the European Alliance of Associations for Rheumatology (EULAR), chronic maintenance therapy with glucocorticoids. The long-term use of glucocorticoids in SLE however, is associated with organ damage and in one study of over 2,000 patients, it was found that a 1mg/day increase in use of the glucocorticoids, in particular prednisolone, was associated with 2.8% increase in the risk of developing new organ damage. Furthermore, even above a relatively low dose of 4.42mg daily, glucocorticoids can still exert damage in SLE. Not surprisingly, clinicians wish to withdraw glucocorticoids, with one survey finding that 96% of clinicians would withdraw an oral steroid after 5 years in serologically quiescent disease, while the patient continued with hydroxychloroquine.

Nevertheless, an important barrier to glucocorticoid withdrawal in systemic lupus erythematous is that the rate of withdrawal is yet to be determined. In a 2020 study abrupt withdrawal of low-dose prednisolone (5mg) in patients with clinically inactive disease was found to increase the incidence of disease flares compared to those who were maintained on the drug over the following 12 months. But what if gradually tapering the dose of glucocorticoid was used instead and this was a question posed by a team from the University of Toronto Lupus Clinic, Ontario, Canada. They decided to explore the impact of slowly reducing the dose of glucocorticoid in systemic lupus erythematous patients who had been in clinical remission for at least 2 years. Patients taking 5mg of prednisolone were instructed to reduce their dose by 1mg/day as follows: in the first week, maintain 5mg daily for six days and reduce to 4mg on day 7; for the second week, maintain at 5mg for 5 days and reduce to 4mg for 2 days; for the third week, maintain 5mg for 4 days and 4mg for three days and so on. At week 7, the patients remained on the reduced dose until their next clinic appointment with an overall aim of stopping the glucocorticoid after 9 to 18 months. The main outcome of interest was the proportion of patients who experienced a disease flare within the 2 years, assessed in terms of the SELDAI-2K score, which is a global index of ongoing disease activity.

Findings
In total, 204 patients with SLE were included and were equally assigned to a withdrawal or maintenance group. In the withdrawal group, the mean age of participants was 44.1 years (90.2% female). The disease flare rate (i.e., an increase in SELDAI-2k) scores occurred in 17.6% of the withdrawal group compared to 29.4% in the maintenance group (p = 0.023) after 12 months. After 24 months, the corresponding flare rates were 33.0% vs 50% (withdrawal vs maintenance, p = 0.01). At 24 months, the proportion of flares requiring an escalation in systemic therapy, was 14.7% vs 27.5% (withdrawal vs maintenance, p = 0.024). Additionally, after 24 months, a higher proportion of patients in the maintenance group accrued new damage (6.9% vs 17.6%, withdrawal vs maintenance, p = 0.022).
The authors discussed how their results indicated that gradual withdrawal of prednisolone in patients with SLE, did not lead to an increased incidence of flares or organ damage over 24 months. They concluded that the gradual withdrawal of glucocorticoids was a much better strategy that abrupt discontinuation and called for this approach to be examined in a randomised trial.

Citation
Tselios K et al. Gradual glucocorticosteroid Withdrawal Is Safe in Clinically Quiescent Systemic Lupus Erythematosus. ARC Open Rheum 2021