Impact of glucocorticoid dose threshold in definition of lupus low disease activity state: a multinational observational cohort study.

OBJECTIVES: This study examined if lowering the glucocorticoid (GC) ceiling in the definition of lupus low disease activity state (LLDAS) from 7.5 mg/day to 5 mg/day (LLDAS-5) was associated with better outcomes in patients with systemic lupus erythematosus (SLE). METHODS: Data from a 13-country longitudinal SLE cohort (American College of Rheumatology/Systemic Lupus International Collaborating Clinics criteria), collected prospectively between 2013 and 2020, were analysed. Survival analyses were used to examine the longitudinal associations of LLDAS definitions with flare, organ damage accrual (frailty models) and mortality (Cox regression models). RESULTS: 3801 patients with ≥2 visits were studied, with a median of 2.8 years (IQR: 1.0-5.4) of follow-up data (total visits: 40 949). 2141 (56.3%) patients experienced mild-moderate/severe flares; 717 (20.8%) accrued organ damage, and 80 (2.1%) died. 3072 (80%) patients attained LLDAS in 19 293 (47%) visits, while 2858 (75%) patients attained LLDAS-5 in 17 403 (42%) visits. Most patients in LLDAS were also in LLDAS-5; 214 patients (5.6%) attained LLDAS on at least one occasion, but never attained LLDAS-5. The magnitude of protection provided by LLDAS attainment against flare, irreversible organ damage accrual and mortality was similar with both GC thresholds. HRs (95% CIs) of damage accrual subsequent to spending 12 months in sustained LLDAS and LLDAS-5 were 0.42 (0.33 to 0.54, p<0.0001) and 0.43 (0.34 to 0.55, p<0.001), respectively. Likewise, HRs of flare and mortality corresponding to 12 months in LLDAS and LLDAS-5 were similar. CONCLUSIONS: No evidence was found to support revising the GC dose threshold of the LLDAS definition. Regardless, minimising GC exposure remains a key goal of SLE management. TRIAL REGISTRATION NUMBER: NCT03138941.