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抗 SARS-CoV-2 疫苗接种和免疫调节治疗的炎症性肠病患者的抗体反应:前瞻性单中心研究。

Anti-SARS-CoV-2 Vaccination and Antibody Response in Patients With Inflammatory Bowel Disease on Immune-modifying Therapy: Prospective Single-Tertiary Study.

机构信息

Clinical and Research Centre for Inflammatory Bowel Disease ISCARE and First Faculty of Medicine, Charles University, Prague, Czech Republic.

GENNET Prague, Czech Republic.

出版信息

Inflamm Bowel Dis. 2022 Oct 3;28(10):1506-1512. doi: 10.1093/ibd/izab301.

Abstract

BACKGROUND

Patients with inflammatory bowel disease (IBD) on immune-modifying treatment could be at an increased risk for severe coronavirus disease 2019 (COVID-19); thus, data on the efficacy and safety of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccines are essential. We conducted a prospective study of IBD patients vaccinated with BNT162b2, CX-024414, and ChAdOx1 nCoV-19 vaccines. The aim was to evaluate the rate and magnitude of seroconversion, assess the effect of different immune-modifying treatment modalities on the magnitude of anti-SARS-CoV-2 IgG antibody levels, and analyze the impact of anti-SARS-CoV-2 vaccination on the inflammatory biomarkers of IBD.

METHODS

The study included 602 IBD patients and 168 immunocompetent health care workers serving as controls. Serum anti-SARS-CoV-2 IgG antibodies were measured by chemiluminescent microparticle immunoassay before the vaccination and 8 weeks after the vaccination.

RESULTS

Of IBD patients, 82.2% were receiving biological treatment: most of them were treated with antitumor necrosis factor (TNF)-α inhibitors (48.5%), and just under half of them were treated with concomitant thiopurines or methotrexate, followed by vedolizumab (18.6%) and ustekinumab (15.1%). Only 8.1% of patients were on 5-aminosalicylates, and a minority (2.2%) were treatment-free. The postvaccine seropositivity rate among IBD patients and controls was 97.8% vs 100%. Median anti-SARS-CoV-2 IgG levels were lower among IBD recipients of ChAdOx1 nCoV-19 compared with 2 other vaccines (P < .0001) and control ChAdOx1 nCoV-19 recipients (P = .01). No correlation was found between serum trough levels and anti-SARS-CoV-2 IgG concentrations for any of the biological drugs used. The TNF-α inhibitors with concomitant immunosuppressive treatment but no other treatment modalities were associated with a lower postvaccination antibody response (P < .0001). When evaluating the laboratory activity of IBD by C-reactive protein and fecal calprotectin levels, no significant differences were found before the vaccination and 8 weeks after its completion.

CONCLUSIONS

Our findings warrant particular attention to the anti-SARS-CoV-2 vaccination of IBD patients treated with TNF-α inhibitors with concomitant immunomodulators and show the priority of mRNA vaccines in this specific group of patients.

摘要

背景

接受免疫调节治疗的炎症性肠病(IBD)患者患严重 2019 年冠状病毒病(COVID-19)的风险可能增加;因此,关于严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)疫苗的疗效和安全性的数据至关重要。我们对接受 BNT162b2、CX-024414 和 ChAdOx1 nCoV-19 疫苗接种的 IBD 患者进行了前瞻性研究。目的是评估血清转化率的速率和幅度,评估不同免疫调节治疗方式对 SARS-CoV-2 IgG 抗体水平幅度的影响,并分析 SARS-CoV-2 疫苗接种对 IBD 炎症生物标志物的影响。

方法

该研究纳入了 602 名 IBD 患者和 168 名免疫功能正常的医护人员作为对照组。在接种疫苗前和接种疫苗 8 周后,通过化学发光微粒子免疫分析法检测血清 SARS-CoV-2 IgG 抗体。

结果

IBD 患者中,82.2%接受生物治疗:大多数患者接受抗肿瘤坏死因子(TNF)-α 抑制剂治疗(48.5%),近一半患者同时接受硫嘌呤或甲氨蝶呤治疗,其次是维得利珠单抗(18.6%)和乌司奴单抗(15.1%)。只有 8.1%的患者接受 5-氨基水杨酸治疗,少数(2.2%)患者未接受治疗。IBD 患者和对照组的疫苗接种后血清阳性率分别为 97.8%和 100%。与其他两种疫苗相比(P<0.0001),接受 ChAdOx1 nCoV-19 疫苗接种的 IBD 患者的 SARS-CoV-2 IgG 中位数较低,与 ChAdOx1 nCoV-19 对照组相比也较低(P=0.01)。对于任何使用的生物药物,均未发现血清谷值水平与 SARS-CoV-2 IgG 浓度之间存在相关性。同时接受免疫抑制治疗但未接受其他治疗方式的 TNF-α 抑制剂与较低的疫苗接种后抗体反应相关(P<0.0001)。在评估 C 反应蛋白和粪便钙卫蛋白水平的 IBD 实验室活动时,在接种疫苗前后 8 周均未发现显著差异。

结论

我们的研究结果特别需要关注接受同时接受免疫调节剂治疗的 TNF-α 抑制剂治疗的 IBD 患者的 SARS-CoV-2 疫苗接种,并表明在这一特定患者群体中,mRNA 疫苗具有优先权。

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