Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Department of Obstetrics and Gynecology, Loma Linda Medical Center, Los Angeles, California, USA.
Am J Reprod Immunol. 2022 Aug;88(2):e13559. doi: 10.1111/aji.13559. Epub 2022 May 12.
We evaluated eculizumab, a complement protein C5 inhibitor, for treatment of severe COVID-19 in pregnant and postpartum individuals.
Protocol ECU-COV-401 (clinicaltrials.gov NCT04355494) is an open label, multicenter, Expanded Access Program (EAP), evaluating eculizumab for treatment of severe COVID-19. Participants enrolled at our center from August 2020 to February 2021. Hospitalized patients were eligible if they had severe COVID-19 with bilateral pulmonary infiltrates and oxygen requirement. Eculizumab was administered on day 1 (1200 mg IV) with additional doses if still hospitalized (1200 mg IV on Days 4 and 8; 900 mg IV on Days 15 and 22; optional doses on Days 12 and 18). The primary outcome was survival at Day 15. Secondary outcomes included survival at Day 29, need for mechanical ventilation, and duration of hospital stay. We evaluated pharmacokinetic and pharmacodynamic data, safety, and adverse outcomes.
Eight participants were enrolled at the Cedars-Sinai Medical Center, six during pregnancy (mean 30 ± 4.0 weeks) and two in the postpartum period. Baseline oxygen requirement ranged from 2 L/min nasal cannula to 12 L/min by non-rebreather mask. The median number of doses of eculizumab was 2 (range 1-3); the median time to hospital discharge was 5.5 days (range 3-12). All participants met the primary outcome of survival at Day 15, and all were alive and free of mechanical ventilation at Day 29. In three participants we demonstrated that free C5 and soluble C5b-9 levels decreased following treatment. There were no serious adverse maternal or neonatal events attributed to eculizumab at 3 months.
We describe use of eculizumab to treat severe COVID-19 in a small series of pregnant and postpartum adults. A larger, controlled study in pregnancy is indicated.
我们评估了补体蛋白 C5 抑制剂依库珠单抗（eculizumab）在妊娠和产后个体中治疗严重 COVID-19 的效果。
方案 ECU-COV-401（clinicaltrials.gov NCT04355494）是一项开放标签、多中心的扩展准入计划（EAP），评估依库珠单抗治疗严重 COVID-19 的效果。我们中心于 2020 年 8 月至 2021 年 2 月期间入组了该方案。如果患者患有伴有双侧肺部浸润和氧需求的严重 COVID-19，则符合住院条件。如果仍在住院，患者在第 1 天（1200mg IV）接受依库珠单抗治疗，如果仍在住院，则在第 4 天和第 8 天（1200mg IV）、第 15 天和第 22 天（900mg IV）给予额外剂量（第 12 天和第 18 天可选剂量）。主要结局为第 15 天的生存情况。次要结局包括第 29 天的生存情况、机械通气的需求和住院时间。我们评估了药代动力学和药效学数据、安全性和不良结局。
8 名参与者在 Cedars-Sinai 医疗中心入组，其中 6 名在妊娠期间（平均 30 ± 4.0 周），2 名在产后。基线时的氧需求范围从 2L/min 鼻导管到 12L/min 非重复呼吸面罩。依库珠单抗的中位数剂量为 2 剂（范围 1-3 剂）；中位数住院时间为 5.5 天（范围 3-12 天）。所有参与者均达到第 15 天的主要生存结局，且所有参与者在第 29 天均存活且无需机械通气。在 3 名参与者中，我们证实治疗后游离 C5 和可溶性 C5b-9 水平下降。在 3 个月时，没有与依库珠单抗相关的严重产妇或新生儿不良事件。
我们描述了在一小部分妊娠和产后成人中使用依库珠单抗治疗严重 COVID-19 的情况。需要在妊娠中进行更大规模的对照研究。
