Update on low-dose glucocorticoids in SLE Save

Glucocorticoids (GC) have been the mainstay of treatment in systemic lupus erythematosus (SLE) for nearly three quarters of a century. Through their genomic and non-genomic actions, GC induce a range of anti-inflammatory effects, quickly relieve some symptoms and lower mortality in some life-threatening flares.

However, they also have multiple side effects that limit the duration of treatment, as well as the dose used. Thus, GC remain a valuable ‘friend’ if used wisely, yet they can become a ‘foe’ if used in excess. Accordingly, the 2023 EULAR recommendations for SLE set a target dose of ≤5mg/day.

Is low dose GC an achievable target?

At the EULAR 2024 congress, Vesentini F et al. (OP0180) presented data on a retrospective study of an inception cohort of SLE in Italy. Following remission, which was defined as clinical SLEDAI-2K=0 on prednisone ≤5 mg/day and/or stable immunosuppressive/antimalarial therapy, they evaluated those who discontinued GCs vs those who maintained GC therapy (≤5 mg/day). Flare-up was defined as any increase in clinical SLEDAI-2K>0 or the need for changes in SLE medications. Of 484 patients who were in remission for at least once visit, 360 (74%) discontinued GC while 124 (26%) remained on low dose GC. During a mean observational time of 87 months, 85 flares were observed. Interestingly, of these, 48 flares were encountered in those who discontinued GC (0.13 flares/patient) and 37 flares in the low dose GC group (0.29 flares/patient) (p<0.01). Similar finding favouring those who discontinued GC was observed in sensitivity analysis looking at those in prolonged remission (i.e. lasted for >2 consecutive years).

Collectively, this study showed that after clinical remission, GC discontinuation after proper tapering appeared safe and was associated with a low risk of flare.

So, since low dose GC appears to be safe from the perspective of disease flare, should we modify our treat to target in clinical research or practice?

The Lupus Low Disease Activity (LLDAS) is a validated target and consists of a) SLEDAI-2K ≤4, with no activity in major organ systems; b) no new lupus disease activity compared with the previous assessment; c) SELENA-SLEDAI physician global assessment ≤1 point; d) a current prednisolone (or equivalent) dose ≤7.5 mg daily; and e) well tolerated standard maintenance doses of immunosuppressive drugs.

Morand E et al. (OP0124) conducted a multicentre cohort study in Asia Pacific to compare the impact of a modified LLDAS by lowering the GC ceiling to 5 mg/day (LLDAS-5) and the legacy LLDAS on mortality, organ damage accrual and disease flare. Of 1933/2213 patients who achieved LLDAS, most patients who were in LLDAS were also in LLDAS-5 (~95%). This study found no difference in the protective effect of spending 12 months in either LLDAS or LLDAS-5 in terms of mortality, organ damage accrual and disease flare. Thus, the current LLDAS definition does not need to be changed. However in clinical practice, with the advance of steroid-sparing therapies including biologics over the last 3 years, lowering GC dose and perhaps discontinuation of therapy should be a key goal of management in SLE.