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

BackgroundLow-dose interleukin-2 (IL-2) shows promise as a treatment for restoring functional and numerical deficits of regulatory T (Treg) cells in patients with various autoimmune diseases. Several clinical trials testing low-dose IL-2 in systemic lupus erythematosus (SLE) have been completed, with a comprehensive review of these trials currently lacking. ObjectiveWe aimed to conduct a systematic synthesis of findings from clinical trials regarding the clinical efficacy and safety of using low-dose IL-2 in patients with SLE. Furthermore, we intended to determine the sensitivity of different responder indices for IL-2-induced clinical improvement in SLE. MethodsFollowing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we searched the Scopus and MEDLINE databases for articles reporting trials testing low-dose IL-2 in patients with SLE published between January 2010 and September 2022. To evaluate the risk of bias, we applied a modified version of the Downs and Black assessment tool. ResultsWe retrieved 1,018 articles, six of which we analyzed including four open-label studies and two randomized controlled trials following a detailed review process. The studies included a total of 230 patients, of which 150 received low dose IL-2 and 80 received placebo. Although the open-label studies demonstrated an expansion of Treg cells that coincided with a clinical response, the predefined primary endpoints for clinical efficacy were not achieved in the randomized controlled trials. In general, treatment with low-dose IL-2 appears to be safe and tolerated well. ConclusionLow-dose IL-2 therapy appears to be a promising strategy for treating SLE; however, larger trials are still necessary to assess clinical responses in patients with such a heterogeneous disease.