Predictors of a successful glucocorticoid tapering and withdrawal in an inception cohort of patients with lupus nephritis and associations with long-term outcomes and damage accrual.

Abstract

Objectives: The optimal duration of glucocorticoid (GC) treatment in lupus nephritis (LN) remains unclear. We examined predictors of GC tapering and discontinuation (D/C), flares during tapering and post-D/C and long-term outcomes.

Methods: We analysed inception cohort data (1992-2021) from 136 patients with LN (median follow-up: 121 months) and applied regression models to assess predictors of successful GC D/C and long-term outcomes, including clinical/laboratory, histological and treatment characteristics.

Results: Median time to 7.5 mg/day, 5 mg/day and GC D/C was 9, 12 and 29 months post-diagnosis, respectively. Composite complete renal response (CR) and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K≤4, sustainedly attained until GC D/C (HR: 1.85, p=0.016), membranous LN (HR: 1.81, p=0.01) and persistent use of hydroxychloroquine (HR: 1.49, p=0.04) were associated with a shorter time to GC D/C. Patients diagnosed after 2010 achieved earlier GC D/C.Shorter time to CR (OR: 1.05, p=0.034) and Lupus Low Disease Activity State at tapering from 7.5 mg/day onwards (OR: 0.23, p=0.046) reduced flare risk during tapering. Definition Of Remission In Systemic Lupus Erythematosus (DORIS) complete remission at D/C (OR: 0.20, p=0.005) and persistent hydroxychloroquine use (OR: 0.28, p=0.031) protected against post-D/C renal flares. Neither higher initial GC dose (>40 mg/day) nor slower GC tapering prevented renal flares. Time to GC D/C (OR: 1.02/month, p=0.04) and flares (OR: 2.08, p=0.036) were associated with damage risk at the end of follow-up.

Conclusion: Sustained CR/SLEDAI-2K≤4, membranous LN and persistent hydroxychloroquine use emerged as main predictors of shorter time to D/C, while DORIS complete remission at D/C and persistent hydroxychloroquine use predicted post-DC flares. Time to GC D/C and flares independently contributed to 10-year damage accrual.