The efficacy and safety of short-term and low-dose IL-2 combined with tocilizumab to treat rheumatoid arthritis

Abstract

Background: Immunotherapy targeting factors related to immune imbalance has been widely employed for RA treatment. This study aimed to evaluate the efficacy and safety of low-dose interleukin (IL)-2 combined with tocilizumab (TCZ), a biologics targeting IL-6, in RA patients.

Methods: Fifty adults with active RA who met the criteria with complete clinical data were recruited, and divided into three groups: control group (n=15), IL-2 group (n=26), and IL-2+TCZ group (n=9). In addition to basic treatment, participants in the IL-2 group received IL-2 (0.5 MIU/day), while participants in the IL-2+TCZ group received IL-2 (0.5 MIU/day) along with one dose of TCZ (8 mg/kg, maximum dose: 800 mg). All subjects underwent condition assessment, laboratory indicators and safety indicators detection, and records before treatment and one week after treatment.

Results: Compared with the baseline, all three groups showed significant improvement in disease conditions, as evidenced by significantly reduced disease activity indicators. The low-dose IL-2 and combination treatment groups demonstrated a violent proliferation of Tregs, while the absolute number of Th1, Th2, and Th17 cells in the latter group showed a decreasing trend. The decrease in the Th17/Treg ratio was more pronounced in the IL-2+TCZ groups. No significant adverse reactions were observed in any of the patients.

Conclusion: Exogenous low doses of IL-2 combined TCZ were found to be safe and effective in reducing effector T cells and appropriately increasing Treg levels in RA patients with high effector T cell levels. This approach helps regulate immune homeostasis and contributes to the prevention of disease deterioration.

Clinical trial registration: https://www.chictr.org.cn/showprojEN.html?proj=13909, identifier ChiCTR-INR-16009546.

Keywords: immunoregulation; low-dose IL-2; rheumatoid arthritis; therapeutics; tocilizumab.

Figure 1

The absolute numbers of peripheral CD4+T lymphocytes (A) and its subsets such as Th1 (B), Th2 (C), Th17 (D), and Treg cells (E) in the control group, IL-2 group, and IL-2+tocilizumab group during the observation period. The levels of Th1/Th2 ratio (F) and Th17/Treg ratio (G) in the above groups were shown. *P < 0.05, **P <0.01, ***P <0.001. The significance level is P<0.05.

Figure 2

Changes of ESR (A), CRP (B), TJC (C), SJC (D), and DAS28-ESR (E) levels in three groups before and after treatment. *P < 0.05, **P <0.01, ***P <0.001. The significance level is P<0.05. ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; TJC, tender joint counts; SJC, swollen joint counts; DAS28, disease activity score-28.

Figure 3

The correlation between the absolute count of circulating Treg cells and the ratio of Th17 to Treg cells and disease activity. The absolute count of Treg cells was negatively correlated with ESR (A), CRP (B), TJC (C), SJC (D), and DAS28-ESR levels (E), while the ratio of Th17 to Treg cells was positively correlated with ESR (F), TJC (G), SJC (H), and DAS28-ESR levels (I). ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; TJC, tender joint counts; SJC, swollen joint counts; DAS28, disease activity score-28; Treg cells, regulatory T cells.