Low-dose IL-2 for active SLE: Phase IIb study results

Results from a multicenter, randomized, double-blind, placebo-controlled phase IIb trial (NCT04077684), evaluating low-dose interleukin-2 (IL-2) in 152 patients with active systemic lupus erythematosus (SLE), were published in Nature Communications by Zhang et al. Study participants were randomized to receive subcutaneous (SC) IL-2 (0.2, 0.5, or 1.0 million international units [MIU]) or placebo every other day for 12 weeks, then weekly for 12 weeks. The primary endpoint was SLE Responder Index 4 (SRI-4) response rate at Week 12. Secondary endpoints included the proportion of patients achieving lupus low disease activity state (LLDAS); change from baseline in SLE Disease Activity Index (SLEDAI) score, physician’s global assessment (PGA) score, and glucocorticoid dose; immune responses; and safety at Weeks 12 and 24. 

Key data: At Week 12, SRI-4 response rates were significantly greater in the 1.0 MIU (69.7%) and 0.5 MIU (64.7%) groups vs placebo (23.5%; both p < 0.001). The proportion of patients achieving LLDAS at Week 12 was greater in the 1.0 MIU (27.3%; p = 0.005) and 0.5 MIU groups (20.6%; p = 0.024) vs placebo (2.9%). A greater reduction in PGA scores was observed at Week 12 in the 1.0 MIU (p = 0.001) and 0.5 MIU (p < 0.001) groups vs placebo. Significant reductions in SLEDAI score were observed in all IL-2 dose groups vs placebo. A significant reduction in corticosteroid dose was demonstrated in the 1.0 MIU group vs placebo at Week 12 (p = 0.041). All differences remained significant until Week 24. IL-2 led to increases in CD4+ T-cell counts and expansion of regulatory T cells (Tregs) in all dose groups. The most common treatment-related adverse event (TRAE) was injection site reaction. 

Key learning: Low-dose IL-2 provides clinically meaningful, dose-dependent disease control in active SLE, with 1.0 MIU delivering the greatest improvement in disease activity and steroid-sparing benefit; these findings require confirmation in phase III trials.