Rheumatology and Therapy (Nov 2023)

Efficacy, Safety and the Lymphocyte Subset Changes of Low-Dose IL-2 in Patients with Autoimmune Rheumatic Diseases: A Systematic Review and Meta-Analysis

  • Qinyi Su,
  • Xinmiao Wang,
  • Yongzhi Li,
  • Jiexiang Zhang,
  • Cairui Bai,
  • Xuechun Wang,
  • Liu Yang,
  • Jingting Zhang,
  • Sheng-Xiao Zhang

DOI
https://doi.org/10.1007/s40744-023-00620-7
Journal volume & issue
Vol. 11, no. 1
pp. 79 – 96

Abstract

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Abstract Introduction Current therapies for autoimmune rheumatic diseases (ARDs) have limited efficacy in certain patients, highlighting the need for the development of novel treatment approaches. This meta-analysis aims to assess the efficacy and safety of low-dose interleukin-2 (LD-IL-2) and evaluate the alterations in lymphocyte subsets in various rheumatic diseases following administration of different dosages of LD-IL-2. Methods A comprehensive search was conducted in PubMed, Web of Science, the Cochrane Library, Embase databases and CNKI to identify relevant studies. A total of 31 trials were included in this meta-analysis. The review protocols were registered on PROSPERO (CRD42022318916), and the study followed the PRISMA guidelines. Results Following LD-IL-2 treatment, patients with ARDs exhibited a significant increase in the number of Th17 cells and Tregs compared to their pre-treatment levels [standardized mean difference (SMD) = 0.50, 95% confidence interval (CI) (0.33, 0.67), P < 0.001; SMD = 1.13, 95% CI (0.97, 1.29), P < 0.001]. Moreover, the Th17/Tregs ratio showed a significant decrease [SMD = − 0.54, 95% CI (− 0.64, − 0.45), P < 0.001]. In patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), LD-IL-2 injection led to a significant increase in Treg numbers, and the Th17/Tregs ratio and disease activity scores, including Disease Activity Score-28 joints (DAS28), Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), were all significantly reduced. No serious adverse events were reported in any of the included studies. Additionally, 54.8% of patients with lupus nephritis achieved distinct clinical remission following LD-IL-2 treatment. Injection site reactions and fever were the most common side effects of LD-IL-2, occurring in 33.1% and 14.4% of patients, respectively. Conclusion LD-IL-2 treatment showed promise and was well tolerated in the management of ARDs, as it effectively promoted the proliferation and functional recovery of Tregs. Trial Registration Retrospectively registered (CRD42022318916, 21/04/2022).

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