Risk of severe COVID-19 outcomes associated with immune-mediated inflammatory diseases and immune-modifying therapies: a nationwide cohort study in the OpenSAFELY platform.
Risk of severe COVID-19 outcomes associated with immune-mediated inflammatory diseases and immune-modifying therapies: a nationwide cohort study in the OpenSAFELY platform.
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与免疫介导的炎症性疾病和免疫调节疗法相关的严重 COVID-19 结果的风险：OpenSAFELY 平台上的一项全国性队列研究。
DOI：
10.1016/s2665-9913(22)00098-4
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发表时间：
2022-07
影响因子：
25.4
通讯作者：
Langan, Sinead M.
中科院分区：
文献类型：
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作者：
MacKenna, Brian;Kennedy, Nicholas A.;Mehrkar, Amir;Rowan, Anna;Galloway, James;Matthewman, Julian;Mansfield, Kathryn E.;Bechman, Katie;Yates, Mark;Brown, Jeremy;Schultze, Anna;Norton, Sam;Walker, Alex J.;Morton, Caroline E.;Harrison, David;Bhaskaran, Krishnan;Rentsch, Christopher T.;Williamson, Elizabeth;Croker, Richard;Bacon, Seb;Hickman, George;Ward, Tom;Davy, Simon;Green, Amelia;Fisher, Louis;Hulme, William;Bates, Chris;Curtis, Helen J.;Tazare, John;Eggo, Rosalind M.;Evans, David;Inglesby, Peter;Cockburn, Jonathan;McDonald, Helen, I;Tomlinson, Laurie A.;Mathur, Rohini;Wong, Angel Y. S.;Forbes, Harriet;Parry, John;Hester, Frank;Harper, Sam;Douglas, Ian J.;Smeeth, Liam;Lees, Charlie W.;Evans, Stephen J. W.;Goldacre, Ben;Smith, Catherine H.;Langan, Sinead M.
免疫介导性炎症性疾病患者和服用免疫调节药物的患者发生严重新冠肺炎结局的风险可能不完全由并存疾病介导，可能会因种族等因素而异。我们的目标是评估患有免疫介导性炎症性疾病的成年人和接受免疫调节治疗的人发生严重新冠肺炎的风险。我们使用OpenSAFELY(电子健康记录分析平台)和TPP(全科医生软件提供商)进行了一项队列研究，分析了常规收集的与入院、死亡和以前无法获得的医院处方数据有关的初级保健数据。我们包括在2020年3月1日年龄在18岁或以上的人，他们在2020年3月之前注册了TPP Practice，至少有12个月的初级保健记录。我们使用COX回归(调整混杂因素和中介因素)来估计风险比(HR)，比较免疫介导性炎症性疾病患者与普通人群、免疫介导性炎症性疾病患者使用靶向免疫调节药物(如生物制剂)与标准全身治疗(如甲氨蝶呤)与标准全身治疗(如甲氨蝶呤)患者新冠肺炎相关死亡、重症监护入院或死亡以及住院(2020年3月1日至9月30日)的风险。我们确定了17名 672 065成年人；1 163 438成年人(640 164[55.0%]女性和523 274[45.0%]男性，827 457[71.1%]白人)患有免疫介导性炎症性疾病；16 508 627人(8 215 020[49.8%]女性和8 293 607[50.2%]男性，10 614 096[·3%])作为一般人群。在1 163 438名成人免疫介导性炎症性疾病患者中，19名 119(1.6%)接受了靶向免疫调节治疗，181名 694(15.6%)接受了标准系统治疗。与普通人群相比，在调整了混杂因素(年龄、性别、剥夺和吸烟状况；HR1·23，95%可信区间1·20-1·27)和进一步调整中介因素(体重指数、心血管疾病、糖尿病和当前使用糖皮质激素；1·15、1·11-1·18)后，患有免疫介导性炎症性疾病的成年人与新冠肺炎相关的死亡风险增加。免疫介导性炎症性疾病的成人入院或死亡的风险也增加(混杂因素调整后的HR 1·24，95%可信区间1·21-1·28；中介因素调整后的1·16，1·12-1·19)和住院(混杂因素调整后的1·32，1·29-1·35；中介调整后的1·20，1·17-1·23)。在事后分析中，患有免疫介导性炎症性疾病的人发生严重新冠肺炎后果的风险在非白人群体中高于白人民族群体(与普通人群一样)。在调整混杂因素(年龄、性别、剥夺、体重指数、免疫介导性炎症性疾病[肠道、关节和皮肤]、心血管疾病、癌症[不包括非黑色素性皮肤癌]、中风和糖尿病(HR 1·03，95%CI为0·80-1·33))和额外调整当前糖皮质激素使用后(1·01，0·78-1·30)后，我们没有看到靶向治疗的成年人与标准系统治疗的患者相比，新冠肺炎相关死亡率增加的证据。与接受标准系统治疗的患者相比，没有证据表明服用肿瘤坏死因子抑制剂、白介素12/白介素23抑制剂、白介素17抑制剂、白介素6抑制剂或Janus激酶抑制剂的成人新冠肺炎相关死亡率增加。利妥昔单抗与新冠肺炎相关死亡增加相关(HR 1·68，95%CI 1·11-2·56)，在排除血液系统恶性肿瘤或器官移植患者后有所减弱(1·54，0·95-2·49)。在患有免疫介导性炎症性疾病的人中，新冠肺炎死亡率和入院人数更高。与接受标准系统治疗的患者相比，使用最有针对性的免疫调节药物治疗免疫介导性炎症性疾病的患者，新冠肺炎不良结局的风险没有增加。英国医学研究理事会、伦敦国王学院的NIHR生物医学研究中心、盖伊和圣托马斯NHS基金会信托基金以及惠康信托基金。
The risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases and on immune-modifying drugs might not be fully mediated by comorbidities and might vary by factors such as ethnicity. We aimed to assess the risk of severe COVID-19 in adults with immune-mediated inflammatory diseases and in those on immune-modifying therapies. We did a cohort study, using OpenSAFELY (an analytics platform for electronic health records) and TPP (a software provider for general practitioners), analysing routinely collected primary care data linked to hospital admission, death, and previously unavailable hospital prescription data. We included people aged 18 years or older on March 1, 2020, who were registered with TPP practices with at least 12 months of primary care records before March, 2020. We used Cox regression (adjusting for confounders and mediators) to estimate hazard ratios (HRs) comparing the risk of COVID-19-related death, critical care admission or death, and hospital admission (from March 1 to Sept 30, 2020) in people with immune-mediated inflammatory diseases compared with the general population, and in people with immune-mediated inflammatory diseases on targeted immune-modifying drugs (eg, biologics) compared with those on standard systemic treatment (eg, methotrexate). We identified 17 672 065 adults; 1 163 438 adults (640 164 [55·0%] women and 523 274 [45·0%] men, and 827 457 [71·1%] of White ethnicity) had immune-mediated inflammatory diseases, and 16 508 627 people (8 215 020 [49·8%] women and 8 293 607 [50·2%] men, and 10 614 096 [64·3%] of White ethnicity) were included as the general population. Of 1 163 438 adults with immune-mediated inflammatory diseases, 19 119 (1·6%) received targeted immune-modifying therapy and 181 694 (15·6%) received standard systemic therapy. Compared with the general population, adults with immune-mediated inflammatory diseases had an increased risk of COVID-19-related death after adjusting for confounders (age, sex, deprivation, and smoking status; HR 1·23, 95% CI 1·20–1·27) and further adjusting for mediators (body-mass index [BMI], cardiovascular disease, diabetes, and current glucocorticoid use; 1·15, 1·11–1·18). Adults with immune-mediated inflammatory diseases also had an increased risk of COVID-19-related critical care admission or death (confounder-adjusted HR 1·24, 95% CI 1·21–1·28; mediator-adjusted 1·16, 1·12–1·19) and hospital admission (confounder-adjusted 1·32, 1·29–1·35; mediator-adjusted 1·20, 1·17–1·23). In post-hoc analyses, the risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases was higher in non-White ethnic groups than in White ethnic groups (as it was in the general population). We saw no evidence of increased COVID-19-related death in adults on targeted, compared with those on standard systemic, therapy after adjusting for confounders (age, sex, deprivation, BMI, immune-mediated inflammatory diseases [bowel, joint, and skin], cardiovascular disease, cancer [excluding non-melanoma skin cancer], stroke, and diabetes (HR 1·03, 95% CI 0·80–1·33), and after additionally adjusting for current glucocorticoid use (1·01, 0·78–1·30). There was no evidence of increased COVID-19-related death in adults prescribed tumour necrosis factor inhibitors, interleukin (IL)-12/IL‑23 inhibitors, IL-17 inhibitors, IL-6 inhibitors, or Janus kinase inhibitors compared with those on standard systemic therapy. Rituximab was associated with increased COVID-19-related death (HR 1·68, 95% CI 1·11–2·56), with some attenuation after excluding people with haematological malignancies or organ transplants (1·54, 0·95–2·49). COVID-19 deaths and hospital admissions were higher in people with immune-mediated inflammatory diseases. We saw no increased risk of adverse COVID-19 outcomes in those on most targeted immune-modifying drugs for immune-mediated inflammatory diseases compared with those on standard systemic therapy. UK Medical Research Council, NIHR Biomedical Research Centre at King's College London and Guy's and St Thomas' NHS Foundation Trust, and Wellcome Trust.