Efficacy and Safety of Low-Dose Interleukin 2 for Behçet’s Syndrome: a Phase 2 Randomized Double-Blind Placebo-Controlled Clinical Trial

Behçet’s syndrome (BS), a chronic relapsing systemic vasculitis, leads to recurrent oral aphthous ulcers, severely impacting quality of life. We conducted a randomized double-blind placebo-controlled clinical trial to evaluate the efficacy and safety of Low-dose interleukin-2 (LD-IL-2) in BS patients. We randomly assigned BS patients (aged 18 to 70 years) with active oral ulcers to receive LD-IL-2 or placebo for 12 weeks (1:1 ratio). The primary endpoint was the oral ulcer count at week 12. Secondary endpoints included the changes in oral ulcer pain (100-mm VAS), overall disease activity and quality of life, genital ulcer count, and complete oral ulcer response rates, along with the change of CD4 + T cell subsets. A total of 60 randomly assigned participants received at least one dose of LD-IL-2 or placebo and 51 completed the trial. The mean number of oral ulcers at week 12 was significantly lower in the LD-IL-2 group than in the placebo group (0.69 ± 1.05 vs. 1.57 ± 0.90, P = 0.001). There were great reductions in oral ulcer pain, the Behçet’s Syndrome Activity Score, the Behcet's Disease Current Activity Index score as well as the Behçet’s Disease Quality of Life scale score in the LD-IL-2 group compared to the placebo group at week 12. No infections or severe adverse events were observed in either group. LD-IL-2 expanded regulatory T cells (Tregs) and decreased the ratio of effector T cell (Teff) to Tregs. LD-IL-2 therapy is an effective and safe treatment in BS patients and is associated with the modulation of Treg and Teffcells.ClinicalTrials.gov registration: NCT04065672.