Kuitwaard Krista, de Gelder Jenny, Tio-Gillen Anne P, Hop Wim C J, van Gelder Teun, van Toorenenbergen Albert W, van Doorn Pieter A, Jacobs Bart C
Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.
Ann Neurol. 2009 Nov;66(5):597-603. doi: 10.1002/ana.21737.
Intravenous immunoglobulin (IVIg) is the first choice treatment for Guillain-Barré syndrome (GBS). All patients initially receive the same arbitrary dose of 2g per kg body weight. Not all patients, however, show a good recovery after this standard dose. IVIg clearance may depend on disease severity and vary between individuals, implying that this dose is suboptimal for some patients. In this study, we determined whether the pharmacokinetics of IVIg is related to outcome in GBS.
We included 174 GBS patients who had previously participated in 2 randomized clinical trials. At entry, all patients were unable to walk unaided and received a standard dose of IVIg. Total IgG levels in serum samples obtained immediately before and 2 weeks after the start of IVIg administration were determined by turbidimetry and related to clinical outcome at 6 months.
The increase in serum IgG (DeltaIgG) 2 weeks after IVIg treatment varied considerably between patients (mean, 7.8g/L; standard deviation, 5.6g/L). Patients with a low DeltaIgG recovered significantly more slowly, and fewer reached the ability to walk unaided at 6 months (log-rank p < 0.001). In multivariate analysis adjusted for other known prognostic factors, a low DeltaIgG was independently associated with poor outcome (p = 0.022).
After a standard dose of IVIg treatment, GBS patients show a large variation in pharmacokinetics, which is related to clinical outcome. This may indicate that patients with a small increase in serum IgG level may benefit from a higher dosage or second course of IVIg.
静脉注射免疫球蛋白(IVIg)是吉兰 - 巴雷综合征(GBS)的首选治疗方法。所有患者最初均接受每公斤体重2g的相同任意剂量治疗。然而,并非所有患者在接受该标准剂量治疗后都能良好恢复。IVIg清除率可能取决于疾病严重程度且因人而异,这意味着该剂量对某些患者并非最佳。在本研究中,我们确定了IVIg的药代动力学是否与GBS的预后相关。
我们纳入了174例先前参与两项随机临床试验的GBS患者。入院时,所有患者均无法独立行走,并接受了标准剂量的IVIg治疗。通过比浊法测定IVIg给药开始前及开始后2周采集的血清样本中的总IgG水平,并将其与6个月时的临床结局相关联。
IVIg治疗2周后患者血清IgG的升高幅度(DeltaIgG)差异很大(平均值为7.8g/L;标准差为5.6g/L)。DeltaIgG较低的患者恢复明显较慢,且在6个月时能够独立行走的人数较少(对数秩检验p < 0.001)。在对其他已知预后因素进行校正的多变量分析中,低DeltaIgG与不良结局独立相关(p = 0.022)。
在接受标准剂量的IVIg治疗后,GBS患者的药代动力学存在很大差异,这与临床结局相关。这可能表明血清IgG水平升高幅度较小的患者可能从更高剂量或第二疗程的IVIg治疗中获益。