Therapeutic immunoglobulin should be dosed by clinical outcome rather than by body weight in obese patients
Therapeutic immunoglobulin should be dosed by clinical outcome rather than by body weight in obese patients
复制标题
DOI：
10.1111/cei.12616
复制
发表时间：
2015-07-01
影响因子：
4.6
通讯作者：
Chapel, H.
中科院分区：
文献类型：
--
作者：
Hodkinson, J. P.;Lucas, M.;Chapel, H.
目前没有数据支持肥胖患者治疗性免疫球蛋白（IG）的剂量应因药代动力学（PK）、安全性和经济原因而封顶的建议。我们比较了接受替代或免疫调节免疫球蛋白治疗的肥胖和消瘦患者的IgG谷水平、增量和效率。31名肥胖患者与一名临床上相当的瘦型患者在一系列适应症中相匹配，包括原发性抗体缺乏或自身免疫性周围神经病变。使用两个中心正在进行的研究数据库进行全面匹配，其中IG的剂量基于临床结局，无论是感染预防还是记录的临床神经系统稳定性。在肥胖和瘦人群之间以及匹配对内，比较了临床稳定时的IgG谷值或稳态水平、IgG增量和IG效率。本研究表明，在人群水平上，与瘦型患者相比，肥胖患者在给定的体重调整剂量下达到了更高的谷值和增量（但不是有效性）。然而，在个体患者水平上，这种相关性存在显著的例外，并且在亚组分析时，在接受替代治疗的肥胖和瘦患者之间没有发现显著差异。在所有剂量方案中，高体重指数（BMI）不能用于可靠地预测临床上适合剂量限制的患者。
There are currently no data to support the suggestion that the dose of therapeutic immunoglobulin (Ig) should be capped in obese patients for pharmacokinetic (PK), safety and economic reasons. We compared IgG trough levels, increment and efficiency in matched pairs of obese and lean patients receiving either replacement or immunomodulatory immunoglobulin therapy. Thirty-one obese patients were matched with a clinically equivalent lean patient across a range of indications, including primary antibody deficiency or autoimmune peripheral neuropathy. Comprehensive matching was carried out using ongoing research databases at two centres in which the dose of Ig was based on clinical outcome, whether infection prevention or documented clinical neurological stability. The IgG trough or steady state levels, IgG increments and Ig efficiencies at times of clinical stability were compared between the obese and lean cohorts and within the matched pairs. This study shows that, at a population level, obese patients achieved a higher trough and increment (but not efficiency) for a given weight-adjusted dose compared with the lean patients. However at an individual patient level there were significant exceptions to this correlation, and upon sub-group analysis no significant difference was found between obese and lean patients receiving replacement therapy. Across all dose regimens a high body mass index (BMI) cannot be used to predict reliably the patients in whom dose restriction is clinically appropriate.