No evidence for hypogammaglobulinemia in patients with paroxysmal nocturnal hemoglobinuria (PNH) chronically treated with ravulizumab.,PLOS ONE

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No evidence for hypogammaglobulinemia in patients with paroxysmal nocturnal hemoglobinuria (PNH) chronically treated with ravulizumab.
PLOS ONE ( IF 2.9 ) Pub Date : 2020-03-27 , DOI: 10.1371/journal.pone.0230869
Ferras Alashkar ₁ , Scott Rottinghaus ₂ , Colin Vance ₃ , Dörte Herich-Terhürne ₁ , Ulrich Dührsen ₁ , Roland Assert ₄ , Alexander Röth ₁

Affiliation

Introduction

Ravulizumab (ALXN1210) is a long-lasting recycling IgG monoclonal antibody with an increased affinity for the neonatal Fc receptor (FcRn). The FcRn is essential for regulating IgG homeostasis. Saturation of the FcRn pathway is seen under high IgG doses as they compete with endogenous IgG to bind the FcRn by their Fc regions, resulting in enhanced IgG clearance.

Patients/Methods

Between Jan 2016 and Jun 2019 (median observation time 21.6 months (6–37.7 months)) serum IgG concentrations and IgG1-4 subclasses were evaluated over a longitudinal course (post-hoc analysis) in 12 ravulizumab-treated adult patients with paroxysmal nocturnal hemoglobinuria (PNH) (58% (7/12) males, median age 50 years (yrs) (18–70 yrs)). All patients were enrolled in one of the three ravulizumab-PNH-related trials (201-, 301-, or 302-study) at the University Hospital Essen.

Results

Baseline IgG concentrations were documented in 11 out of the 12 patients prior to ravulizumab treatment (median IgG 9.9 g/L (5–13.5 g/L)). In two female patients a clinically not relevant hypogammaglobulinemia with an associated IgG1 or a combined IgG1/IgG2 deficiency prior to treatment was documented. The data were further stratified with regard to various treatment intervals as multiple analyses were obtained. Throughout observation time IgG concentrations remained within physiologic ranges with no evidence of a treatment-related IgG depletion (median IgG at study endpoint 10.1 g/L (6–13.4 g/L)).

Conclusion

In ravulizumab-treated PNH patients, IgG and IgG subclass levels which are regulated by the FcRn remained unaffected. Therefore, no treatment associated hypogammaglobulinemia is to be feared under chronic ravulizumab therapy.

中文翻译：

没有证据表明长期接受拉维珠单抗治疗的阵发性睡眠性血红蛋白尿症 (PNH) 患者存在低丙种球蛋白血症。

介绍

Ravulizumab (ALXN1210) 是一种长效循环 IgG 单克隆抗体，对新生儿 Fc 受体 (FcRn) 具有更高的亲和力。 FcRn 对于调节 IgG 稳态至关重要。在高 IgG 剂量下可以看到 FcRn 途径饱和，因为它们与内源 IgG 竞争通过其 Fc 区结合 FcRn，从而导致 IgG 清除率增强。

患者/方法

2016年1月至2019年6月（中位观察时间21.6个月（6-37.7个月））期间，对12名接受ravulizumab治疗的阵发性睡眠性血红蛋白尿症成年患者进行纵向过程（事后分析）评估血清IgG浓度和IgG1-4亚类(PNH)（58% (7/12) 男性，中位年龄 50 岁（18-70 岁））。所有患者均参加了埃森大学医院的三项 ravulizumab-PNH 相关试验（201、301 或 302 研究）之一。

结果

在 ravulizumab 治疗前，12 名患者中有 11 名记录了基线 IgG 浓度（中位 IgG 9.9 g/L (5–13.5 g/L)）。在两名女性患者中，记录了治疗前临床上不相关的低丙种球蛋白血症，伴有 IgG1 或联合 IgG1/IgG2 缺乏。当获得多重分析时，数据根据不同的治疗间隔进一步分层。在整个观察期间，IgG 浓度保持在生理范围内，没有证据表明治疗相关的 IgG 消耗（研究终点的中位 IgG 为 10.1 g/L (6–13.4 g/L)）。