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炎症性肠病患者对 COVID-19 疫苗的反应降低,但增加剂量可改善。

Response to COVID-19 vaccine is reduced in patients with inflammatory bowel disease, but improved with additional dose.

机构信息

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Laboratory Diagnostics, Tohoku University Hospital, Sendai, Japan.

出版信息

J Gastroenterol Hepatol. 2023 Jan;38(1):44-51. doi: 10.1111/jgh.16001. Epub 2022 Sep 21.

Abstract

BACKGROUND

Coronavirus disease 2019 (COVID-19) vaccination is recommended for patients with inflammatory bowel disease (IBD); however, suppressed immune responses have been reported for fully vaccinated patients under immunosuppressive therapy, mainly from Western countries. We prospectively analyzed antibody titers of IBD patients in Asia induced by two-dose and additional dose of messengerRNA COVID-19 vaccine.

METHODS

After measuring high-affinity antibody titers, factors associated with antibody titers were identified by multiple regression analyses using the following covariates: sex, age (≥60 or <60 years), disease type (Crohn's disease or ulcerative colitis), vaccine type (BNT162b2 or mRNA-1273), time from second/third vaccination, molecular-targeted agent (anti-tumor necrosis factor [TNF] agents, ustekinumab, vedolizumab, tofacitinib, or no molecular-targeted agents), thiopurine, steroid, and 5-aminosalicylic acid.

RESULTS

Among 409 patients analyzed, mean titer was 1316.7 U/mL (SD, 1799.3); 403 (98.5%) were judged to be seropositive (≥0.8 U/mL), and 389 (95.1%) had neutralizing antibodies (≥15 U/mL). After the third vaccination, mean titer raised up to 21 123.8 U/mL (SD, 23 474.5); all 179 were seropositive, and 178 (99.4%) had neutralizing antibodies. In 248 patients with genetic data, there was no difference in mean titer after two/third doses between carriers and non-carriers of HLA-A24 associated with severe disease during COVID-19 infection. A multiple regression analyses using covariates revealed that older age, vaccine type (BNT162b2), time from second/third dose, anti-TNF agent, tofacitinib, and thiopurine were independently associated with lower antibody titers.

CONCLUSIONS

Our findings further support the recommendation for COVID-19 vaccination in patients under immunosuppressive therapy, especially additional third dose for patients receiving anti-TNF agents and/or thiopurine or tofacitinib.

摘要

背景

建议患有炎症性肠病(IBD)的患者接种 2019 年冠状病毒病(COVID-19)疫苗;然而,在接受免疫抑制治疗的完全接种疫苗的患者中,已经报道了免疫反应受到抑制的情况,主要来自西方国家。我们前瞻性地分析了亚洲 IBD 患者接种两剂和额外剂量信使 RNA COVID-19 疫苗后的抗体滴度。

方法

在测量高亲和力抗体滴度后,通过多元回归分析使用以下协变量确定与抗体滴度相关的因素:性别、年龄(≥60 岁或<60 岁)、疾病类型(克罗恩病或溃疡性结肠炎)、疫苗类型(BNT162b2 或 mRNA-1273)、第二次/第三次接种时间、靶向分子药物(抗肿瘤坏死因子[TNF]药物、乌司奴单抗、vedolizumab、托法替尼或无靶向分子药物)、硫嘌呤、皮质类固醇和 5-氨基水杨酸。

结果

在分析的 409 名患者中,平均滴度为 1316.7 U/mL(标准差,1799.3);403 名(98.5%)被判定为血清阳性(≥0.8 U/mL),389 名(95.1%)具有中和抗体(≥15 U/mL)。第三次接种后,平均滴度升高至 21123.8 U/mL(标准差,23474.5);179 名均为血清阳性,178 名(99.4%)具有中和抗体。在有遗传数据的 248 名患者中,在 COVID-19 感染期间与疾病严重程度相关的 HLA-A24 携带者和非携带者中,两/三剂后平均滴度无差异。使用协变量的多元回归分析显示,年龄较大、疫苗类型(BNT162b2)、第二次/第三次剂量时间、抗 TNF 药物、托法替尼和硫嘌呤与较低的抗体滴度独立相关。

结论

我们的研究结果进一步支持对接受免疫抑制治疗的患者进行 COVID-19 疫苗接种的建议,特别是对接受抗 TNF 药物和/或硫嘌呤或托法替尼的患者进行额外的第三剂接种。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdd0/9537921/b4f080b27087/JGH-9999-0-g003.jpg

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