Department of Anesthesia and Intensive Care, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy.
Faculty of Medicine, Vita-Salute San Raffaele University, Milan, Italy.
Front Immunol. 2022 Jul 25;13:932251. doi: 10.3389/fimmu.2022.932251. eCollection 2022.
A great number of anti-inflammatory drugs have been suggested in the treatment of SARS-CoV-2 infection. Reparixin, a non-competitive allosteric inhibitor of the CXCL8 (IL-8) receptors C-X-C chemokine receptor type 1 (CXCR1) and C-X-C chemokine receptor type 2 (CXCR2), has already been tried out as a treatment in different critical settings. Due to the contrasting existing literature, we decided to perform the present meta-analysis of randomized controlled trials (RCTs) to investigate the effect of the use of reparixin on survival in patients at high risk for in-hospital mortality.
We created a search strategy to include any human RCTs performed with reparixin utilization in patients at high risk for in-hospital mortality, excluding oncological patients. Two trained, independent authors searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) for appropriate studies. Furthermore, references of review articles and included RCTs were screened to identify more studies. No language restrictions were enforced. To assess the risk of bias of included trials, the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2) was used.
Overall, six studies were included and involved 406 patients (220 received reparixin and 186 received the comparator). The all-cause mortality in the reparixin group was significantly lower than that in the control group [5/220 (2.3%) in the reparixin group vs. 12/186 (6.5%) in the control group, odds ratio = 0.33 (95% confidence interval 0.12 to 0.96), -value for effect 0.04, for heterogeneity 0.20, = 36%]. In addition, no difference in the rate of pneumonia, sepsis, or non-serious infections was shown between the two groups.
Our meta-analysis of randomized trials suggests that short-term inhibition of CXCL8 activity improved survival in patients at high risk for in-hospital mortality without increasing the risk of infection.
META-ANALYSIS REGISTRATION: PROSPERO, identifier CRD42021254467.
针对 SARS-CoV-2 感染，已经提出了大量的抗炎药物。Reparixin 是一种非竞争性的 CXCL8（IL-8）受体 C-X-C 趋化因子受体 1（CXCR1）和 C-X-C 趋化因子受体 2（CXCR2）的别构抑制剂，已经在不同的危急情况下被尝试作为一种治疗方法。由于现有的文献存在差异，我们决定进行这项随机对照试验（RCTs）的荟萃分析，以研究使用 Reparixin 对住院高死亡率风险患者的生存影响。
我们创建了一个搜索策略，纳入了使用 Reparixin 治疗住院高死亡率风险患者的所有人类 RCTs，但排除了肿瘤患者。两名经过培训的、独立的作者在 PubMed、EMBASE 和 Cochrane 对照试验中心注册库（CENTRAL）中搜索了合适的研究。此外，还筛选了综述文章和纳入 RCT 的参考文献，以确定更多的研究。没有对语言进行限制。为了评估纳入试验的偏倚风险，使用了修订后的 Cochrane 随机试验偏倚风险工具（RoB 2）。
共有 6 项研究纳入了 406 名患者（Reparixin 组 220 名，对照组 186 名）。Reparixin 组的全因死亡率明显低于对照组[Reparixin 组 5/220（2.3%），对照组 12/186（6.5%），比值比=0.33（95%置信区间 0.12 至 0.96），值为 0.04，异质性值为 0.20，=36%]。此外，两组之间肺炎、败血症或非严重感染的发生率没有差异。
我们对随机试验的荟萃分析表明，短期抑制 CXCL8 活性可提高住院高死亡率风险患者的生存率，而不会增加感染风险。
PROSPERO，标识符 CRD42021254467。
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