Hartinger Jan Miroslav, Satrapová Veronika, Hrušková Zdenka, Tesař Vladimír
Institute of Pharmacology, Department of Clinical Pharmacology and Pharmacy, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
Department of Nephrology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
Eur J Hosp Pharm. 2019 Jul;26(4):210-213. doi: 10.1136/ejhpharm-2017-001454. Epub 2018 Feb 28.
According to the manufacturer's documentation, rituximab (RTX) should be administered with slow infusion rates to prevent infusion-related adverse events (AEs). Nevertheless, slow infusions are time-consuming and uncomfortable for patients and medical staff. Therefore, faster infusion rates have been studied and proven safe and well tolerated in lymphomas and rheumatoid arthritis (RA). A small amount of data is available for rapid RTX infusions in non-RA autoimmune diseases.
Beginning in September 2015, all RTX-reated patients in our centre and willing to participate, were switched from slow RTX infusions (4.25 hours, given at least once to all patients) to fast infusions (2 hours). A total of 85 RTX 2-hour infusions was administered to 53 patients with autoimmune diseases with renal involvement and selected primary glomerulonephritides (26 ANCA-associated vasculitis, nine systemic lupus erythematodes, seven membranous nephropathy, five IgM nephropathy and six other autoimmune disease). Most of the patients received chronic corticosteroid therapy. The prednisone equivalent dose median (IQR) was 0.1 (0.0-0.2) mg/kg/day.
Rapid RTX infusions were generally well tolerated. Only two infusion-related AEs were recorded: one Common Terminology Criteria for Adverse Events, grade 3, (lower back pain and hypotension followed by chills necessitating methylprednisolone and dipyrone administration) and one grade 1 (subjective intolerance). The AEs frequency does not differ from other studies with rapid RTX infusions in patients with lymphomas and RA.
Our experience supported other published data and provides evidence concerning the safety of non-initial RTX 2-hour infusion which can be administered without raising the infusion-related AEs rate in patients with kidney-affecting autoimmune diseases and glomerulonephritides.
根据制造商的文件，利妥昔单抗（RTX）应以缓慢输注速度给药，以预防输注相关不良事件（AE）。然而，缓慢输注对患者和医护人员来说既耗时又不舒服。因此，已经对更快的输注速度进行了研究，并证明在淋巴瘤和类风湿关节炎（RA）中是安全且耐受性良好的。在非RA自身免疫性疾病中，关于快速RTX输注的可用数据较少。
从2015年9月开始，我们中心所有接受RTX治疗且愿意参与的患者，从缓慢RTX输注（4.25小时，所有患者至少给药一次）改为快速输注（2小时）。共对53例有肾脏受累的自身免疫性疾病患者和选定的原发性肾小球肾炎患者（26例抗中性粒细胞胞浆抗体相关性血管炎、9例系统性红斑狼疮、7例膜性肾病、5例IgM肾病和6例其他自身免疫性疾病）进行了85次2小时的RTX输注。大多数患者接受慢性糖皮质激素治疗。泼尼松等效剂量中位数（IQR）为0.1（0.0 - 0.2）mg/kg/天。
快速RTX输注总体耐受性良好。仅记录到两例输注相关AE：一例为3级不良事件通用术语标准（下背痛和低血压，随后寒战，需要给予甲泼尼龙和安乃近），一例为1级（主观不耐受）。这些AE的发生率与其他关于淋巴瘤和RA患者快速RTX输注的研究无差异。
我们的经验支持其他已发表的数据，并提供了关于非初始2小时RTX输注安全性的证据，在影响肾脏的自身免疫性疾病和肾小球肾炎患者中，这种输注方式不会提高输注相关AE的发生率。
