Combination of clinical factors predicts successful glucocorticoid withdrawal in systemic lupus erythematosus (SLE): results from a multicentre, retrospective cohort study

Objective Glucocorticoid (GC) tapering and withdrawal to reduce damage represents a key aspect of the European Alliance of Associations for Rheumatology (EULAR) SLE recommendations. However, optimal strategies for relapse-free GC cessation remain ill-defined. We characterised clinical predictors and their combined effect on flares in patients with SLE who discontinued GC. Methods Retrospective cohort of 324 patients with active SLE (PGA >= 1.5 and/or SLEDAI-2K >= 6) who received GC as part of treatment intensification (median follow-up 60 months). Survival and generalised linear models estimated SELENA-SLEDAI flare risks and their predictors. Results GCs were discontinued in 220 (67.9%) patients with 1-year risks for overall and severe flares of 50% and 25%, respectively (HR: 1.48; 95% CI: 1.12 to 1.96 for overall flares; HR: 1.52; 95% CI: 1.03 to 2.25 for severe flares, compared with non-withdrawers). Flare risk was lowered when GCs were ceased during remission (DORIS) or Lupus Low Disease Activity State (LLDAS; excluding remission) (HR for severe flares: 0.23; 0.12 to 0.43 and 0.30; 0.18 to 0.50, respectively), with each additional month in targets providing further protection. Hydroxychloroquine prevented total (HR: 0.37; 0.26 to 0.53) and severe flares (HR: 0.33; 0.21 to 0.52), while mycophenolate and azathioprine reduced overall flares. Prednisone tapering from 7.5 mg/day to 0 over >6 months improved severe flare-free outcome (HR: 0.57; 0.37 to 0.90). Random survival forests identified DORIS/LLDAS, hydroxychloroquine use and slow GC tapering as top predictors, whose coexistence reduced overall and severe flares by similar to 25 fold and similar to 50 fold, respectively. This combination reduced damage (IRR: 0.31; 0.08 to 0.84) without inducing flares (IRR: 0.52; 95% CI: 0.18 to 1.16) compared with GC non-withdrawers. Conclusion Low or absent disease activity, slow tapering and hydroxychloroquine use minimise the risk of flares, facilitating GC discontinuation-a major goal in SLE.