Shovman O, Shoenfeld Y, Langevitz P
Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center, 52621, Tel-Hashomer, Israel.
Immunol Res. 2015 Feb;61(1-2):164-8. doi: 10.1007/s12026-014-8590-4.
One of the adverse events of tocilizumab (TCZ) is a transient, dose-dependent neutropenia. The recommendations of the Summary of Product Characteristics state that this neutropenia should be managed according to the absolute neutrophil count (ANC). However, the approach to a patient who had a history of neutropenia induced by previous DMARDs and developed TCZ-induced neutropenia remains unclear. We would like to report a series of four patients with rheumatoid arthritis who developed Grade 2 neutropenia (ANC 1-1.5 × 10(9)/L) following intravenous TCZ treatment at a dose of 8 mg/kg. All of them had a previous history of neutropenia (Grade 2 or Grade 3) due to Etanercept (three patients) and Sulfasalazine (one patient). Therefore, we decided to decrease the TCZ dosage by 10-20% approximately. Reducing of the dosage did not have any influence on the efficacy of TCZ, and all of our patients remained in clinical remission. The mechanisms underlying neutropenia induced by Tocilizumab, Etanercept and Sulfasalazine are also discussed in this article.
托珠单抗(TCZ)的不良反应之一是短暂的、剂量依赖性中性粒细胞减少。产品特性摘要中的建议指出,这种中性粒细胞减少应根据绝对中性粒细胞计数(ANC)进行处理。然而,对于既往使用传统改善病情抗风湿药(DMARDs)诱发过中性粒细胞减少且又发生了TCZ诱发的中性粒细胞减少的患者,处理方法仍不明确。我们想报告4例类风湿关节炎患者,他们在静脉注射8mg/kg剂量的TCZ后出现了2级中性粒细胞减少(ANC为1 - 1.5×10⁹/L)。他们均有既往因使用依那西普(3例患者)和柳氮磺胺吡啶(1例患者)导致中性粒细胞减少(2级或3级)的病史。因此,我们决定将TCZ剂量大约降低10% - 20%。剂量降低对TCZ的疗效没有任何影响,我们所有的患者均保持临床缓解状态。本文还讨论了托珠单抗、依那西普和柳氮磺胺吡啶诱发中性粒细胞减少的潜在机制。