Immunosuppressant withdrawal versus glucocorticoid withdrawal in SLE: 2-year outcomes of a noninferiority randomized controlled trial.

Abstract

This study aimed to test whether immunosuppressant (IS) withdrawal is noninferior to glucocorticoid (GC) withdrawal in patients with SLE in remission. In this open-label, single-centre, 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 endpoint 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 to 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 to 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.