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聚乙二醇非格司亭与聚乙二醇化重组人粒细胞刺激因子及非格司亭用于减少化疗引起的中性粒细胞减少相关事件的荟萃分析及间接治疗比较

Meta-analysis and indirect treatment comparison of lipegfilgrastim with pegfilgrastim and filgrastim for the reduction of chemotherapy-induced neutropenia-related events.

作者信息

Bond T Christopher, Szabo Erika, Gabriel Susan, Klastersky Jean, Tomey Omar, Mueller Udo, Schwartzberg Lee, Tang Boxiong

机构信息

1 Covance Market Access, Gaithersburg, MD, USA.

2 Teva Pharmaceuticals, Frazer, PA, USA.

出版信息

J Oncol Pharm Pract. 2018 Sep;24(6):412-423. doi: 10.1177/1078155217714859. Epub 2017 Jun 14.

Abstract

Background Granulocyte colony-stimulating factors are effective at reducing the risk and duration of neutropenia. The current meta-analysis compared the neutropenia-related efficacy and safety of lipegfilgrastim to those of pegfilgrastim and filgrastim. Methods Embase was searched for trials examining the efficacy/safety of lipegfilgrastim, pegfilgrastim, or filgrastim. Outcomes included febrile neutropenia, severe neutropenia, duration of severe neutropenia, time to recovery of absolute neutrophil count, and incidence of bone pain. Direct comparisons were made using random-effects models. No trials directly compared lipegfilgrastim and filgrastim. Indirect comparisons were made between lipegfilgrastim and filgrastim with pegfilgrastim as the common comparator. Results This meta-analysis included a total of 5769 patients from 24 studies. Over all cycles, lipegfilgrastim showed a lower, nonsignificant risk of febrile neutropenia compared with pegfilgrastim. Lipegfilgrastim has a lower risk of febrile neutropenia versus filgrastim but was also not statistically significant. The risk ratio for severe neutropenia in cycle 1 was 0.80, a 20% reduction in favor of lipegfilgrastim. For cycles 2-4, the risk ratio was 0.53 (0.35, 0.79) for lipegfilgrastim versus pegfilgrastim. The risk of severe neutropenia in cycles 2-4 was also significantly lower for lipegfilgrastim (risk ratio 0.45, 0.27, 0.75, respectively). No significant differences were found for febrile neutropenia and severe neutropenia in cycle 1. However, in cycles 2-4, lipegfilgrastim was associated with significant and clinically meaningful reductions in risk of severe neutropenia versus either pegfilgrastim or filgrastim. Conclusions Compared with pegfilgrastim or filgrastim, lipegfilgrastim has a statistically significantly lower absolute neutrophil count recovery time; however, differences in duration of severe neutropenia and bone pain were nonsignificant.

摘要

背景 粒细胞集落刺激因子在降低中性粒细胞减少症的风险和持续时间方面有效。当前的荟萃分析比较了聚乙二醇化重组人粒细胞刺激因子与聚乙二醇化非格司亭和非格司亭在中性粒细胞减少症相关疗效和安全性方面的差异。方法 在Embase数据库中检索有关聚乙二醇化重组人粒细胞刺激因子、聚乙二醇化非格司亭或非格司亭疗效/安全性的试验。结局指标包括发热性中性粒细胞减少症、严重中性粒细胞减少症、严重中性粒细胞减少症的持续时间、绝对中性粒细胞计数恢复时间以及骨痛发生率。采用随机效应模型进行直接比较。没有试验直接比较聚乙二醇化重组人粒细胞刺激因子和非格司亭。以聚乙二醇化非格司亭作为共同对照,对聚乙二醇化重组人粒细胞刺激因子和非格司亭进行间接比较。结果 该荟萃分析共纳入了来自24项研究的5769例患者。在所有疗程中,与聚乙二醇化非格司亭相比,聚乙二醇化重组人粒细胞刺激因子出现发热性中性粒细胞减少症的风险较低,但差异无统计学意义。与非格司亭相比,聚乙二醇化重组人粒细胞刺激因子出现发热性中性粒细胞减少症的风险较低,但同样无统计学意义。第1疗程严重中性粒细胞减少症的风险比为0.80,聚乙二醇化重组人粒细胞刺激因子更具优势,降低了20%。在第2 - 4疗程中,聚乙二醇化重组人粒细胞刺激因子与聚乙二醇化非格司亭相比的风险比为0.53(0.35,0.79)。聚乙二醇化重组人粒细胞刺激因子在第2 - 4疗程中严重中性粒细胞减少症的风险也显著更低(风险比分别为0.45、0.27、0.75)。在第1疗程中,发热性中性粒细胞减少症和严重中性粒细胞减少症未发现显著差异。然而,在第2 - 4疗程中,与聚乙二醇化非格司亭或非格司亭相比,聚乙二醇化重组人粒细胞刺激因子严重中性粒细胞减少症的风险有显著且具有临床意义的降低。结论 与聚乙二醇化非格司亭或非格司亭相比,聚乙二醇化重组人粒细胞刺激因子的绝对中性粒细胞计数恢复时间在统计学上显著更短;然而,严重中性粒细胞减少症的持续时间和骨痛方面的差异无统计学意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b24/6094503/d61bf1b3ec28/10.1177_1078155217714859-fig1.jpg

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