Low dose IL-2 therapy restores regulatory T cells in patients with systemic lupus erythematosus in a dose-dependent manner: a phase IIb trial

Abstract

Low-dose interleukin 2 (Ld-IL2) has shown therapeutic effects in autoimmune diseases, particularly systemic lupus erythematosus (SLE), yet optimal dosage has not been established in clinical trials. In this multicentre, double-blind, phase IIb trial, 152 patients with active SLE were randomised (1:1:1:1) to receive subcutaneous IL2 (0.2, 0.5, or 1.0 million IU) or placebo every other day for 12 weeks, then weekly for another 12 weeks. At week 12, SRI-4 response rates were higher in the IL2 1 M IU (69.7%), 0.5 M IU (64.7%), and 0.2 M IU (42.9%) groups than the placebo control group (23.5%). Notably, these differences persisted until week 24 (P < 0.001). Moreover, achievement of LLDAS increased in a dose-dependent manner. Patients who received 1 M IU also showed significant reductions in PGA scores, anti-dsDNA antibody titres and prednisone dosages. Infection rates were lower in the IL2 groups compared with placebo. Ld-IL2 drove the expansion of regulatory T cells (Tregs) and altered Treg/effector T cell ratios. These findings highlight the dose-dependent efficacy of IL2 with a favourable safety profile. (Clinicaltrials.gov registration number: NCT04077684).