US Department of Veterans Affairs, PBM, Center for Medication Safety , Hines, Illinois, USA.
Atlanta Veterans Affairs Medical Center , Decatur, Georgia, USA.
mBio. 2023 Aug 31;14(4):e0102423. doi: 10.1128/mbio.01024-23. Epub 2023 Aug 3.
Little is known regarding the effectiveness of tixagevimab/cilgavimab in preventing SARS-CoV-2 infection in vaccinated immunocompromised patients, particularly after the emergence of the Omicron variant. In this retrospective cohort study with exact matching and propensity score adjustment within the U.S. Department of Veterans Affairs (VA) healthcare system, we selected immunocompromised veterans age ≥18 years as of 1 January 2022, receiving VA healthcare. We compared a cohort of 1,878 patients treated with at least one dose of intramuscular tixagevimab/cilgavimab to 7,014 matched controls selected from patients who met study criteria but were not treated. Patients were followed through 15 June 2022, or until death, whichever occurred earlier. The primary outcome was a composite of SARS-CoV-2 infection, COVID-19-related hospitalization, and all-cause mortality. We used Cox proportional hazards modeling to estimate the hazard ratios (HRs) and 95% CI for the association between receipt of tixagevimab/cilgavimab and outcomes. Most (73%) tixagevimab/cilgavimab recipients were ≥65 years old, and 80% had ≥3 mRNA vaccine doses or two doses of Ad26.COV2. Compared to matched controls, recipients had a lower incidence of the composite COVID-19 outcome (49/1,878 [2.6%] versus 312/7,014 [4.4%]; HR 0.35; 95% CI, 0.24-0.52), and individually SARS-CoV-2 infection (HR 0.44; 95% CI, 0.22-0.88), COVID-19 hospitalization (HR 0.24; 95% CI, 0.10-0.59), and all-cause mortality (HR 0.32; 95% CI, 0.19-0.55). In conclusion, tixagevimab/cilgavimab was associated with lower rates of SARS-CoV-2 infection and severe COVID-19 during the Omicron BA.1, BA.2, and BA.2.12.1 surge. IMPORTANCE SARS-CoV-2 remains an ongoing global health crisis that justifies continued efforts to validate and expand, when possible, knowledge on the efficacy of available vaccines and treatments. Clinical trials have been limited due to fast tracking of medications for mitigation of the COVID-19 pandemic for the general population. We present a real-world analysis, using electronic health record data, of the effectiveness of tixagevimab/cilgavimab for the prevention of COVID-19 infection in the unique population of U.S. veterans. Unlike those in the PROVENT clinical trial from which the emergency use authorization for tixagevimab/cilgavimab as a preventative treatment arose, the veterans population is highly immunocompromised and nearly 96% totally vaccinated. These demographics allowed us to analyze the effectiveness of tixagevimab/cilgavimab in preventing COVID-19 under different conditions in a more fragile population than that of the initial clinical trial.
关于替沙格韦单抗/西加韦单抗在预防接种免疫功能低下患者中的 SARS-CoV-2 感染的有效性，特别是在奥密克戎变异株出现后，人们知之甚少。在这项在美国退伍军人事务部 (VA) 医疗保健系统内进行的回顾性队列研究中，我们选择了截至 2022 年 1 月 1 日年龄≥18 岁、接受 VA 医疗保健的免疫功能低下的退伍军人。我们将至少接受一剂肌肉内替沙格韦单抗/西加韦单抗治疗的 1878 名患者的队列与从符合研究标准但未接受治疗的患者中选择的 7014 名匹配对照进行了比较。患者随访至 2022 年 6 月 15 日，或至死亡，以先发生者为准。主要结局是 SARS-CoV-2 感染、COVID-19 相关住院和全因死亡率的复合结局。我们使用 Cox 比例风险模型估计接受替沙格韦单抗/西加韦单抗与结局之间的关联的风险比 (HR) 和 95%置信区间。大多数 (73%)替沙格韦单抗/西加韦单抗接受者≥65 岁，80%接受者≥3 剂 mRNA 疫苗或两剂 Ad26.COV2。与匹配对照相比，接受者的 COVID-19 复合结局发生率较低 (1878 例中有 49 例[2.6%]，7014 例中有 312 例[4.4%]；HR 0.35；95%CI，0.24-0.52)，单独 SARS-CoV-2 感染发生率较低 (HR 0.44；95%CI，0.22-0.88)、COVID-19 住院率较低 (HR 0.24；95%CI，0.10-0.59)和全因死亡率较低 (HR 0.32；95%CI，0.19-0.55)。总之，替沙格韦单抗/西加韦单抗与奥密克戎 BA.1、BA.2 和 BA.2.12.1 浪潮期间 SARS-CoV-2 感染和严重 COVID-19 的发生率较低相关。重要性 SARS-CoV-2 仍然是一场持续的全球健康危机，这证明有必要继续努力验证和扩大现有疫苗和治疗方法的有效性，如有可能。由于为减轻 COVID-19 大流行对普通人群的影响而快速跟踪药物，临床试验受到限制。我们使用电子健康记录数据，对替沙格韦单抗/西加韦单抗在预防美国退伍军人 COVID-19 感染方面的有效性进行了真实世界分析。与替沙格韦单抗/西加韦单抗紧急使用授权作为预防治疗出现的 PROVENT 临床试验中的患者不同，退伍军人人群的免疫功能严重受损，几乎 96%的人完全接种了疫苗。这些人口统计学特征使我们能够在比最初的临床试验更脆弱的人群中分析替沙格韦单抗/西加韦单抗在不同条件下预防 COVID-19 的有效性。
