Phase IIb Trial Shows Low-Dose IL-2 Effective in SLE
A phase IIb trial demonstrated that low-dose IL-2 therapy produced dose-dependent improvements in SLE patients, with 69.7% achieving SRI-4 response at the highest dose versus 23.5% on placebo. A separate systematic review found IL-17 inhibitors remain potential SLE treatment options, though efficacy data are limited.
In a multicentre, double-blind, phase IIb trial, low-dose interleukin-2 (IL-2) demonstrated dose-dependent efficacy and a favorable safety profile in patients with active systemic lupus erythematosus (SLE). The study, which randomised 152 patients to receive subcutaneous IL-2 at three different doses or placebo, found that SRI-4 response rates at week 12 were significantly higher in all IL-2 groups compared to placebo.
Patients were randomised (1:1:1:1) to receive subcutaneous IL-2 at 0.2, 0.5, or 1.0 million IU or placebo every other day for 12 weeks, followed by weekly dosing for another 12 weeks. At week 12, the SRI-4 response rates were 69.7% in the 1.0 million IU group, 64.7% in the 0.5 million IU group, and 42.9% in the 0.2 million IU group, compared with 23.5% in the placebo group. These differences persisted until week 24 (P < 0.001).
Achievement of the Lupus Low Disease Activity State (LLDAS) increased in a dose-dependent manner. Patients who received the highest dose (1 million IU) also showed significant reductions in Physician Global Assessment scores, anti-dsDNA antibody titers, and prednisone dosages. Notably, infection rates were lower in the IL-2 groups compared with placebo. The treatment drove the expansion of regulatory T cells (Tregs) and altered the Treg/effector T cell ratio. The trial was registered at Clinicaltrials.gov under number NCT04077684.
Separately, a systematic literature review has evaluated the safety and potential efficacy of interleukin-17 (IL-17) inhibition in SLE. The review, covering searches from inception to June 2025, examined four IL-17 inhibitors: secukinumab, bimekizumab, brodalumab, and ixekizumab. All agents inhibit IL-17A, with bimekizumab also blocking IL-17A/F.
Across 56 clinical trials of secukinumab in other indications, no cases of drug-induced or paradoxical SLE were reported. No cases of SLE were reported with bimekizumab or ixekizumab, though two cases of ixekizumab-induced lupus tumidus were noted but excluded from the analysis. One case of new-onset SLE was reported in a patient treated with brodalumab for psoriasis.
The review identified four published case reports describing secukinumab use in patients with known active SLE. The most common indications were active cutaneous lupus and inflammatory arthritis (75%, n=3), with one patient (25%) having lupus nephritis. All four patients were ANA and dsDNA positive. Six cases of SLE following secukinumab initiation were identified in the literature, with four reports describing secukinumab being used to treat SLE.
The authors concluded that while rare paradoxical reactions have been described, IL-17 inhibitors remain a potential therapeutic option in SLE. All reported cases of IL-17 inhibitor-induced lupus resolved after withdrawal of the agent, with most requiring only symptomatic management. However, efficacy data remain extremely limited and heterogeneous, and further translational research and dedicated clinical studies are required to clarify the role of IL-17 in SLE pathogenesis.