背景:随着人群药代动力学(PK)建模更容易获得,并且PK指导的预防被当前的血友病指南认可,我们进行了系统综述,以总结文献中的现有证据.
目的:评估PK指导的预防与非PK指导的预防的疗效。
方法:我们没有将纳入限制在特定的研究设计标签上,并且纳入了由至少一个接受PK指导预防的不同队列组组成的所有研究。从开始到搜索日期,我们搜索了以下数据库:MEDLINE,Embase,中部,ClinicalTrials.gov,和欧盟临床试验注册。标题之后,abstract,以及由两位综述作者独立进行的全文筛选,我们通过拟合随机效应模型对研究进行了定性总结,并对纳入的随机临床试验(RCT)进行了定量综合.
结果:在2023年2月3日的数据库搜索中,有25项研究符合我们的纳入标准。其中,只有2项RCT和17项非随机研究纳入了标准预防比较组.此外,后者的偏见风险很大,主要是由于前后研究设计和回顾性比较组。因此,非随机研究仅定性地进行.对两个确定的RCT的随机效应荟萃分析在出血结局(均值1.15的比率;95CI,0.85-1.56)和因子消耗(均值0.82的比率;95CI,0.58-1.18)方面仍然没有定论。
结论:文献中的证据表明PK指导优于标准固定剂量预防的临床益处是微弱的,主要见于缺乏并行对照的非随机研究。结果报告中的异质性,小样本量,和高风险的偏见。
With population pharmacokinetic (PK) modeling more readily available and PK-guided prophylaxis endorsed by current hemophilia guidelines, we conducted a systematic
review to summarize current evidence in the literature.
To assess the efficacy of PK-guided compared with non-PK-guided prophylaxis.
We did not restrict inclusion to specific study design labels and included all studies consisting of at least one distinct cohort arm receiving PK-guided prophylaxis. We searched the following databases from inception to date of search: MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and the EU Clinical Trial Register. Following title, abstract, and full-text screening conducted independently by 2
review authors, we summarized studies qualitatively and synthesized included randomized clinical trials (RCTs) quantitatively by fitting random-effects models.
Search of databases on February 3, 2023, yielded 25 studies fitting our inclusion criteria. Of those, only 2 RCTs and 17 nonrandomized studies included a standard prophylaxis comparator group. Furthermore, risk of bias in the latter was substantial, primarily due to before-after study designs and retrospective comparator groups. Thus, nonrandomized studies were only presented qualitatively. A random-effects meta-analysis of the 2 identified RCT remained inconclusive with regards to bleeding outcomes (ratio of means, 1.15; 95% CI, 0.85-1.56) and factor consumption (ratio of means, 0.82; 95% CI, 0.58-1.18).
Evidence in the literature suggesting a clinical benefit of PK-guided over standard fixed-dose prophylaxis was weak and mainly found in nonrandomized studies limited by lack of concurrent controls, heterogeneity in outcome reporting, small sample sizes, and high risk of bias.