Low-dose interleukin-2 for the treatment of systemic lupus erythematosus: A systematic review and meta-analysis.

OBJECTIVES: Low-dose interleukin-2 (IL-2) is a rational therapy for a variety of autoimmune disorders as it leads to expansion and improved functionality of regulatory T (Treg) cells. In this study, we reviewed the clinical efficacy of IL-2 in patients diagnosed with systemic lupus erythematosus (SLE). METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched the Scopus and MEDLINE databases for clinical trials reporting standardized outcomes of clinical efficacy after treatment with low-dose IL-2 in SLE. Our primary outcome was clinical efficacy, defined as a change in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score. Secondary endpoints included clinical and laboratory markers of disease activity and safety. We computed mean differences and 95% confidence intervals (CIs) using a random effects model. Heterogeneity was assessed by I2 and τ2 statistics. RESULTS: Of 1448 screened articles, nine were selected, including six open-label and three randomized controlled trials. In total, the trials included 584 SLE patients treated with low-dose IL-2 and 140 receiving conventional treatment or placebo. Patients treated with low-dose IL-2 exhibited significant decreases in the SLEDAI score (mean difference - 4.62 [95% CI -5.83, -3.4], I2 = 94.4%, τ2 = 3.569), corresponding to reduced anti-double-stranded DNA (anti-dsDNA) antibody titers alongside increases in complement C3 and C4, and Treg counts. Controlled studies only partially achieved statistically significant results, but displayed a consistent trend toward higher response rates and prednisone reductions in the IL-2 groups. Few, mostly minor adverse events were reported. CONCLUSION: Low-dose IL-2 therapy may offer a promising and safe approach for the treatment of SLE. However, larger controlled trials will be needed to determine the magnitude and clinical relevance of its effects.