Background

Tocilizumab is a monoclonal antibody that interrupts interleukin-6 signalling, reducing downstream effects on inflammation and the innate immune response. It was shown to reduce mortality in patients with severe or critical coronavirus disease 2019 (COVID-19). Pregnant and breastfeeding people were largely excluded from clinical trials and hence, the extent to which results can be applied to these populations is not clear.

Objectives

To synthesize published data on tocilizumab in pregnancy and lactation, highlight important knowledge gaps, and help inform clinical decision-making about tocilizumab's use in these populations with COVID-19.

Sources

PubMed was searched for studies evaluating tocilizumab in pregnancy and lactation for COVID-19 and other indications. Literature on pharmacokinetics and reproductive/fetal safety of monoclonal antibodies in general was also sought. The US Food and Drug Administration and the European Medicines Agency guidance for the industry and regulatory approval documents were reviewed.

Content

Published data on tocilizumab in pregnancy include 610 cases (n = 20 with COVID-19) together with seven mother–infant breastfeeding pairs. Higher rates of spontaneous abortion and premature birth have been reported compared with the general population, but multiple confounding variables limit interpretation. There is little data on tocilizumab exposure in the second and third trimesters when transplacental transport is highest. The effects of tocilizumab on the developing immune system are unclear. Pregnant patients with COVID-19 who received tocilizumab were often critically ill and corticosteroid use was uncommon. Neonatal follow up was limited. Tocilizumab appears to be compatible with breastfeeding.

Implications

Although the available data do not raise serious safety signals, they have significant limitations and are not sufficient to delineate the complete spectrum of potential adverse outcomes that may be associated with tocilizumab exposure during pregnancy and lactation. Diligent follow up and documentation of pregnancy outcomes will be important moving forward. A more effective regulatory framework to ensure equitable inclusion of pregnant people in research is clearly needed.

中文翻译：

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Tocilizumab 治疗妊娠期和哺乳期 2019 冠状病毒病：叙述性综述

背景

Tocilizumab 是一种单克隆抗体，可中断白细胞介素 6 信号传导，减少对炎症和先天免疫反应的下游影响。它被证明可以降低 2019 年严重或危重冠状病毒病 (COVID-19) 患者的死亡率。孕妇和哺乳期人群在很大程度上被排除在临床试验之外，因此，结果可在多大程度上适用于这些人群尚不清楚。

目标

综合已发表的关于托珠单抗在妊娠和哺乳期的数据，突出重要的知识差距，并帮助为临床决策提供关于托珠单抗在这些 COVID-19 人群中的使用信息。

来源

在 PubMed 中搜索了评估妊娠期和哺乳期托珠单抗治疗 COVID-19 和其他适应症的研究。还寻求了关于单克隆抗体的一般药代动力学和生殖/胎儿安全性的文献。美国食品和药物管理局和欧洲药品管理局对行业指南和监管批准文件进行了审查。

内容

已发表的妊娠期托珠单抗数据包括 610 例（ 20 例COVID  -19）以及 7 对母婴母乳喂养。据报道，与一般人群相比，自然流产和早产的发生率更高，但多个混杂变量限制了解释。关于经胎盘转运最高的妊娠中期和晚期托珠单抗暴露的数据很少。托珠单抗对发育中的免疫系统的影响尚不清楚。接受托珠单抗治疗的 COVID-19 孕妇通常病情危重，使用皮质类固醇并不常见。新生儿随访有限。Tocilizumab 似乎与母乳喂养相容。

启示

尽管现有数据没有提出严重的安全信号，但它们有很大的局限性，并且不足以描述可能与怀孕和哺乳期间接触托珠单抗相关的潜在不良后果的完整范围。勤奋的跟进和记录妊娠结果将是重要的进步。显然需要一个更有效的监管框架来确保孕妇公平地参与研究。