Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Laboratory Diagnostics, Tohoku University Hospital, Sendai, Japan.
J Gastroenterol Hepatol. 2023 Jan;38(1):44-51. doi: 10.1111/jgh.16001. Epub 2022 Sep 21.
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.
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.
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.
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.
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。
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。
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。
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。