Cilgavimab and tixagevimab as pre-exposure prophylaxis in vaccine non-responder kidney transplant recipients during a period of prevalent SARS-CoV-2 BA.2 and BA.4/5 variants-a prospective cohort study (RESCUE-TX).

IF 9.7 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL EBioMedicine Pub Date : 2024-11-01 Epub Date: 2024-10-22 DOI:10.1016/j.ebiom.2024.105417

Roman Reindl-Schwaighofer, Andreas Heinzel, Lukas Raab, Robert Strassl, Carsten T Herz, Florina Regele, Konstantin Doberer, Oliver Helk, Paul Spechtl, Constantin Aschauer, Karin Hu, Rahel Jagoditsch, Bianca Reiskopf, Georg A Böhmig, Bernhard Benka, Benedikt Mahr, Karin Stiasny, Lukas Weseslindtner, Michael Kammer, Thomas Wekerle, Rainer Oberbauer

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Abstract

Background: The response to severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccination is severely impaired in patients on maintenance immunosuppression after kidney transplantation.

Methods: We conducted a prospective cohort study of 194 kidney transplant recipients (KTR) who exhibited no response to SARS-CoV-2 vaccinations (i.e., SARS-CoV-2 spike protein antibodies ≤264 U/mL) and had no prior documented infection. Patients received 300 mg of cilgavimab/tixagevimab as SARS-CoV-2 pre-exposure prophylaxis (PrEP) between March 4, 2022, and May 3, 2022 and were contrasted to a matched cohort of 186 KTRs also without immunization again defined as SARS-CoV-2 spike protein antibodies ≤264 U/mL and no documented prior infection. The primary outcome was the serum kinetics of cilgavimab/tixagevimab, the secondary endpoints were time to SARS-CoV-2 breakthrough infection, severity of disease and variant specific live viral in vitro neutralization tests of patient sera.

Findings: Longitudinal serum level monitoring showed a half-life of 91 days for both antibodies (95% CI 86-95 days for cilgavimab and 85-96 days for tixagevimab) in KTRs. In vitro neutralization tests showed effectiveness against the BA.2 omicron subvariant but not BA.5. The cumulative incidence of SARS-CoV-2 infections until May 15, 2022, (BA.2 dominance) was 15/194 vs 36/186 in the PrEP and control group respectively (OR = 0.35, 95% CI 0.18-0.66) but was not different thereafter (BA.4/5 dominance). The number of severe infections during the BA.2 period was lower in the prophylaxis than in the control group (OR = 0.37, 95% CI 0.17-0.79).

Interpretation: This study showed that SARS-CoV-2 PrEP with cilgavimab/tixagevimab demonstrated clinical effectiveness against variants that are neutralised (BA.2) but not against BA.4/5.

Funding: This study was funded by the Medical University of Vienna and an unrestricted grant from AstraZeneca (ESR-21-21585).

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在SARS-CoV-2 BA.2和BA.4/5变种流行期间，将西格维单抗和替沙格列单抗作为疫苗非应答肾移植受者的暴露前预防药物--一项前瞻性队列研究（RESCUE-TX）。

背景：肾移植后接受维持性免疫抑制的患者对严重急性呼吸系统综合征冠状病毒 2 型（SARS-CoV-2）疫苗接种的反应严重受损：肾移植后接受维持性免疫抑制的患者对严重急性呼吸系统综合征冠状病毒 2 型（SARS-CoV-2）疫苗接种的反应严重受损：我们对194名肾移植受者（KTR）进行了前瞻性队列研究，这些患者对SARS-CoV-2疫苗接种无反应（即SARS-CoV-2尖峰蛋白抗体≤264 U/mL），且之前无感染记录。患者在 2022 年 3 月 4 日至 2022 年 5 月 3 日期间接受了 300 毫克的西格维单抗/替沙格韦单抗作为 SARS-CoV-2 暴露前预防（PrEP），并与 186 名同样未接受免疫接种的 KTR（定义为 SARS-CoV-2 尖峰蛋白抗体≤264 U/mL，且无记录在案的既往感染）进行了对比。主要结果是西格维单抗/替沙格列单抗的血清动力学，次要终点是 SARS-CoV-2 突破性感染时间、疾病严重程度和患者血清的变异特异性活病毒体外中和试验：纵向血清水平监测显示，两种抗体在 KTR 中的半衰期均为 91 天（95% CI 为西格维单抗 86-95 天，替沙格单抗 85-96 天）。体外中和试验显示，对 BA.2 omicron 亚变体有效，但对 BA.5 无效。在2022年5月15日之前（BA.2占主导地位），PrEP组和对照组的SARS-CoV-2感染累计发生率分别为15/194 vs 36/186（OR = 0.35，95% CI 0.18-0.66），但之后（BA.4/5占主导地位）没有差异。在 BA.2 期间，预防组的严重感染人数低于对照组（OR = 0.37，95% CI 0.17-0.79）：这项研究表明，使用西格维单抗/替沙格列单抗的SARS-CoV-2预防性治疗对中和变异株（BA.2）具有临床疗效，但对BA.4/5没有疗效：本研究由维也纳医科大学和阿斯利康公司（ESR-21-21585）无限制资助。

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来源期刊

EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology

CiteScore

17.70

自引率

0.90%

发文量

579

审稿时长

5 weeks

期刊介绍： eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.