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Meta-Analysis
. 2021 Sep 21:12:749266.
doi: 10.3389/fimmu.2021.749266. eCollection 2021.

Meta-Analysis of Interleukin-2 Receptor Antagonists as the Treatment for Steroid-Refractory Acute Graft- Versus-Host Disease

Meng-Zhu Shen  1 , Jing-Xia Li  1   2 , Xiao-Hui Zhang  1 , Lan-Ping Xu  1   3 , Yu Wang  1 , Kai-Yan Liu  1 , Xiao-Jun Huang  1   3   4 , Shen-Da Hong  5 , Xiao-Dong Mo  1   3
Affiliations
Meta-Analysis

Meta-Analysis of Interleukin-2 Receptor Antagonists as the Treatment for Steroid-Refractory Acute Graft- Versus-Host Disease

Meng-Zhu Shen et al. Front Immunol. .

Abstract

Acute graft-versus-host disease (aGVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (HSCT). Corticosteroid is the first-line treatment for aGVHD, but its response rate is only approximately 50%. At present, no uniformly accepted treatment for steroid-refractory aGVHD (SR-aGVHD) is available. Blocking interleukin-2 receptors (IL-2Rs) on donor T cells using pharmaceutical antagonists alleviates SR-aGVHD. This meta-analysis aimed to compare the efficacy and safety of four commercially available IL-2R antagonists (IL-2RAs) in SR-aGVHD treatment. A total of 31 studies met the following inclusion criteria (1): patients of any race, any sex, and all ages (2); those diagnosed with SR-aGVHD after HSCT; and (3) those using IL-2RA-based therapy as the treatment for SR-aGVHD. The overall response rate (ORR) at any time after treatment with basiliximab and daclizumab was 0.81 [95% confidence interval (CI): 0.74-0.87)] and 0.71 (95% CI: 0.56-0.82), respectively, which was better than that of inolimomab 0.54 (95% CI: 0.39-0.68) and denileukin diftitox 0.56 (95% CI: 0.35-0.76). The complete response rate (CRR) at any time after treatment with basiliximab and daclizumab was 0.55 (95% CI: 0.42-0.68) and 0.42 (95%CI: 0.29-0.56), respectively, which was better than that of inolimomab 0.30 (95% CI: 0.16-0.51) and denileukin diftitox 0.37 (95% CI: 0.24-0.52). The ORR and CRR were better after 1-month treatment with basiliximab and daclizumab than after treatment with inolimomab and denileukin diftitox. The incidence of the infection was higher after inolimomab treatment than after treatment with the other IL-2RAs. In conclusion, the efficacy and safety of different IL-2RAs varied. The response rate of basiliximab was the highest, followed by that of daclizumab. Prospective, randomized controlled trials are needed to compare the efficacy and safety of different IL-2RAs.

Keywords: acute graft-versus-host disease; interleukin-2 receptor antagonist; meta-analysis; second-line treatment; steroid-refractory.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Selection scheme of studies. GVHD, graft-versus-host disease; HSCT, hematopoietic stem cell transplant; SOT, solid organ transplant.
Figure 2
Figure 2
Forest plots of ORR at any time (A) and 1 month (B) after treatment with IL-2RAs.
Figure 3
Figure 3
Forest plots of CRR at any time (A) and 1 month (B) after treatment with IL-2RAs.
Figure 4
Figure 4
Overall survival rates of patients after treatment with IL-2RAs.
See this image and copyright information in PMC

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