Adverse events linked with the use of chimeric and humanized anti-CD20 antibodies in children with idiopathic nephrotic syndrome
Adverse events linked with the use of chimeric and humanized anti-CD20 antibodies in children with idiopathic nephrotic syndrome
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DOI：
10.1111/bcp.13548
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发表时间：
2018-06-01
影响因子：
3.4
通讯作者：
Ghiggeri, Gian Marco
中科院分区：
文献类型：
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作者：
Bonanni, Alice;Calatroni, Marta;Ghiggeri, Gian Marco
目的抗 CD20 抗体越来越多地用于治疗儿童特发性肾病综合征 (INS)。虽然它们可能允许停用类固醇和钙调神经磷酸酶抑制剂，但通常需要重复输注抗 CD20 抗体才能维持缓解。需要有关其在 INS 中的潜在毒性的数据，以考虑重复输注。方法我们调查了在国家转诊中心治疗 9 年期间（400 次治疗；随访）的 INS（类固醇依赖性和类固醇/钙调神经磷酸酶抑制剂依赖性疾病）儿童中使用利妥昔单抗（一种嵌合抗体；130 名患者）和奥法木单抗（一种人源化抗体；37 名患者）相关的副作用1-9岁）。结果患有类固醇依赖性疾病的儿童主要不存在输注反应。通过使用沙丁胺醇进行术前用药，皮疹、呼吸困难、发烧、咳嗽和喉咙发痒（利妥昔单抗和奥法木单抗输注后分别为 5% 和 18%）得到缓解。其他短期反应（长达 3 个月），包括关节炎 (2%) 和肺损伤 (1%)，在利妥昔单抗治疗中更为常见。输注后 3-9 个月观察到感染，这在两组中同样常见，并通过靶向治疗 [抗生素、氟康唑、免疫球蛋白 (Igs) 等] 得到解决。循环CD19/20细胞数量在第1个月降至0，并在第3个月重建；循环 IgG 抗体在一年内保持在正常范围内。破伤风和乙型肝炎病毒免疫接种均未因这两种治疗方法而改变；偶尔观察到Epstein-Barr病毒和John Cunningham病毒激活标记。结论总体而言，抗CD20单克隆抗体的毒性仅限于患有更复杂疾病的儿童的输注后副作用。抗 CD20 抗体相对安全的特性支持其在患有 INS 的儿童中用作类固醇节省剂。
AimsAnti-CD20 antibodies are increasingly being used to treat idiopathic nephrotic syndrome (INS) in children. While they may allow steroid and calcineurin inhibitor withdrawal, repeated infusions of anti-CD20 antibodies are often required to maintain remission. Data on their potential toxicity in INS are needed, to consider repeated infusions.MethodsWe investigated the side effects associated with the use of rituximab (a chimeric antibody; 130 patients) and ofatumumab (a humanized antibody; 37 patients) in children with INS (steroid-dependent and steroid/calcineurin inhibitor-dependent disease) treated at a national referral centre over a 9-year period (400 treatments; follow-up 1-9years).ResultsInfusion reactions were mainly absent in children with steroid-dependent disease. Rash, dyspnoea, fever, cough and itchy throat (5% and 18% following rituximab and ofatumumab infusion, respectively) were resolved by using premedication with salbutamol. Other short-term reactions (up to 3months), including arthritis (2%) and lung injury (1%), were more common with rituximab. Infections were observed 3-9months following infusion, were similarly common in the two groups and resolved with targeted therapies [antibiotic, fluconazole, immunoglobulins (Igs), etc.]. The number of circulating CD19/20 cells fell to 0 at month 1 and were reconstituted at month 3; circulating IgG antibodies remained within the normal range for 1year. Tetanus and hepatitis B virus immunization was not modified by either treatment; Epstein-Barr virus and John Cunningham virus activation markers were occasionally observed.ConclusionOverall, the toxicity of anti-CD20 monoclonal antibodies was limited to post-infusion side effects in children with more complex disease. The relatively safe profile of anti-CD20 antibodies supports their use as steroid-sparing agents in children with INS.