Efficacy, safety and the lymphocyte subsets changes of low‐dose IL‐2 in patients with systemic lupus erythematosus: A systematic review and meta‐analysis

Abstract

AbstractIntroductionExisting therapies of systemic lupus erythematosus (SLE) are efficacious only in certain patients. Developing new treatment methods is urgent. This meta‐analysis aimed to evaluate the efficacy and safety of low‐dose IL‐2 (LD‐IL‐2).MethodsAccording to published data from PubMed, Web of Science, Embase, ClinicalTrials.gov, MEDLINE, MEDLINE, Web of Knowledge, Cochrane Library, and FDA.gov, eight trials were included.ResultsAfter the LD‐IL‐2 treatment, 54.8% of patients had distinct clinical remission. The SRI‐4 response rates were 0.819 (95% confidence interval [CI]: 0.745–0.894), and the SELENA‐SLEDAI scores were significantly decreased (SMD = −2.109, 95% CI: [−3.271, −0.947], p < .001). Besides, the proportions of CD4+ T (SMD = 0.614, 95% CI: [0.250, 0.979], p = .001) and Treg cells (SMD = 1.096, 95% CI: [0.544, 1.649], p < .001) were increased dramatically after LD‐IL‐2 treatment, while there were no statistical differences in the proportions of CD8+ T cells, Th1 cells, Th2 cells, and Th17 cells (p > .05). Besides, the proportions of Th17 (SMD = 1.121, 95% CI: [0.709, 1.533], p < .001) and Treg (SMD = 0.655, 95% CI: [0.273, 1.038], p = .001) were significantly increased after receiving subcutaneously 0.5 million IU of LD‐IL‐2 treatment per day for 5 days, but there were no statistical differences in the proportions of Treg after receiving 1 million IU every other day subcutaneously of LD‐IL‐2 treatment. Injection site reaction and fever were common side effects of IL‐2, which occurred in 33.1% and 14.4% of patients. No serious adverse events were reported.ConclusionLD‐IL‐2 was promising and well‐tolerated in treating SLE, which could promote Treg's proliferation and functional recovery. Injecting 0.5 million IU of IL‐2 daily can better induce the differentiation of Treg cells and maintain immune homeostasis than injecting 1 million IU every other day.