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免疫抑制药物的长期使用与新冠肺炎住院结局:一项使用国家新冠队列协作项目数据的回顾性队列研究

Long-term use of immunosuppressive medicines and in-hospital COVID-19 outcomes: a retrospective cohort study using data from the National COVID Cohort Collaborative.

作者信息

Andersen Kathleen M, Bates Benjamin A, Rashidi Emaan S, Olex Amy L, Mannon Roslyn B, Patel Rena C, Singh Jasvinder, Sun Jing, Auwaerter Paul G, Ng Derek K, Segal Jodi B, Garibaldi Brian T, Mehta Hemalkumar B, Alexander G Caleb

机构信息

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

出版信息

Lancet Rheumatol. 2022 Jan;4(1):e33-e41. doi: 10.1016/S2665-9913(21)00325-8. Epub 2021 Nov 15.

Abstract

BACKGROUND

Many individuals take long-term immunosuppressive medications. We evaluated whether these individuals have worse outcomes when hospitalised with COVID-19 compared with non-immunosuppressed individuals.

METHODS

We conducted a retrospective cohort study using data from the National COVID Cohort Collaborative (N3C), the largest longitudinal electronic health record repository of patients in hospital with confirmed or suspected COVID-19 in the USA, between Jan 1, 2020, and June 11, 2021, within 42 health systems. We compared adults with immunosuppressive medications used before admission to adults without long-term immunosuppression. We considered immunosuppression overall, as well as by 15 classes of medication and three broad indications for immunosuppressive medicines. We used Fine and Gray's proportional subdistribution hazards models to estimate the hazard ratio (HR) for the risk of invasive mechanical ventilation, with the competing risk of death. We used Cox proportional hazards models to estimate HRs for in-hospital death. Models were adjusted using doubly robust propensity score methodology.

FINDINGS

Among 231 830 potentially eligible adults in the N3C repository who were admitted to hospital with confirmed or suspected COVID-19 during the study period, 222 575 met the inclusion criteria (mean age 59 years [SD 19]; 111 269 [50%] male). The most common comorbidities were diabetes (23%), pulmonary disease (17%), and renal disease (13%). 16 494 (7%) patients had long-term immunosuppression with medications for diverse conditions, including rheumatological disease (33%), solid organ transplant (26%), or cancer (22%). In the propensity score matched cohort (including 12 841 immunosuppressed patients and 29 386 non-immunosuppressed patients), immunosuppression was associated with a reduced risk of invasive ventilation (HR 0·89, 95% CI 0·83-0·96) and there was no overall association between long-term immunosuppression and the risk of in-hospital death. None of the 15 medication classes examined were associated with an increased risk of invasive mechanical ventilation. Although there was no statistically significant association between most drugs and in-hospital death, increases were found with rituximab for rheumatological disease (1·72, 1·10-2·69) and for cancer (2·57, 1·86-3·56). Results were generally consistent across subgroup analyses that considered race and ethnicity or sex, as well as across sensitivity analyses that varied exposure, covariate, and outcome definitions.

INTERPRETATION

Among this cohort, with the exception of rituximab, there was no increased risk of mechanical ventilation or in-hospital death for the rheumatological, antineoplastic, or antimetabolite therapies examined.

FUNDING

None.

摘要

背景

许多人长期服用免疫抑制药物。我们评估了这些人感染新冠病毒住院时的预后是否比未接受免疫抑制治疗的人更差。

方法

我们进行了一项回顾性队列研究,使用来自美国国家新冠队列协作组(N3C)的数据,这是美国最大的确诊或疑似新冠病毒住院患者纵向电子健康记录库,时间跨度为2020年1月1日至2021年6月11日,涵盖42个医疗系统。我们将入院前使用免疫抑制药物的成年人与未长期接受免疫抑制治疗的成年人进行了比较。我们考虑了总体免疫抑制情况,以及15类药物和免疫抑制药物的三种主要适应症。我们使用Fine和Gray的比例亚分布风险模型来估计有创机械通气风险的风险比(HR),同时考虑死亡这一竞争风险。我们使用Cox比例风险模型来估计住院死亡的HR。模型采用双重稳健倾向评分方法进行调整。

结果

在N3C数据库中,在研究期间因确诊或疑似新冠病毒感染而住院的231830名潜在符合条件的成年人中,222575人符合纳入标准(平均年龄59岁[标准差19];111269人[50%]为男性)。最常见的合并症是糖尿病(23%)、肺部疾病(17%)和肾脏疾病(13%)。16494名(7%)患者因多种疾病长期接受免疫抑制治疗,包括风湿性疾病(33%)、实体器官移植(26%)或癌症(22%)。在倾向评分匹配队列中(包括12841名接受免疫抑制治疗的患者和29386名未接受免疫抑制治疗的患者),免疫抑制与有创通气风险降低相关(HR 0.89,95%置信区间0.83 - 0.96),长期免疫抑制与住院死亡风险之间总体无关联。所检查的15类药物中,没有一类与有创机械通气风险增加相关。虽然大多数药物与住院死亡之间无统计学显著关联,但发现治疗风湿性疾病的利妥昔单抗(1.72,1.10 - 2.69)和治疗癌症的利妥昔单抗(2.57,1.86 - 3.56)与住院死亡风险增加有关。在考虑种族、民族或性别的亚组分析以及改变暴露、协变量和结局定义的敏感性分析中,结果总体一致。

解读

在该队列中,除利妥昔单抗外,所检查的风湿性、抗肿瘤或抗代谢疗法并未增加机械通气或住院死亡风险。

资金来源

无。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a05/8592562/d27077f7ecc5/gr1_lrg.jpg

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