Immunosuppressant withdrawal versus glucocorticoid withdrawal in systemic lupus erythematosus: 2-year outcomes of a noninferiority randomized controlled trial

This study aimed to test whether immunosuppressant (IS) withdrawal is noninferior to glucocorticoid (GC) withdrawal in patients with Systemic Lupus Erythematosus (SLE) in remission. In this open-label, single-center, randomized (1:1) controlled trial, we compared flare occurrence in stable SLE patients undergoing GC or IS tapering. Patients aged >18, on stable GC (prednisolone ≤7.5 mg/day) and maintenance non-biological IS for ≥3 years, in clinical remission for ≥1 year, were enrolled and assigned to taper GC or IS over 3 months. The primary end point was the proportion of patients experiencing a flare, defined by the SELENA-SLEDAI Flare Index (SFI) at 52 weeks. Patients in remission beyond 52 weeks were followed up to the maximum available follow-up duration beyond 104 weeks. Between May and December 2021, 121 patients were randomized, and 117 (GC withdrawal, n = 58; IS withdrawal, n = 59) were included in the primary analysis. Flare occurred in 31% of the GC withdrawal group and 20.3% in the IS withdrawal group (risk difference, 10.6%[95% CI, -26.5-5.1]; p= 0.18), demonstrating the noninferiority of IS withdrawal. At maximum follow-up, 44.8% in the GC withdrawal group and 32.2% in the IS withdrawal group experienced a flare (risk difference, -12.6%[95% CI, -30.1-4.9]; p= 0.11), confirming the noninferiority of IS withdrawal at 2 years. Damage accrual was similar between the two groups at both endpoints. IS withdrawal is noninferior to GC withdrawal in SLE patients in long-term clinical remission. Personalized tapering strategies based on baseline damage and steroid exposure may optimize outcomes. The trial was registered with https://ctri.nic.in/, CTRI/2020/07/026712.