Jørgensen Kristin Kaasen, Høivik Marte Lie, Chopra Adity, Benth Jūratė Šaltytė, Ricanek Petr, Moum Prof Bjørn, Jyssum Ingrid, Bolstad Nils, Warren David John, Vaage Prof John T, Munthe Prof Ludvig A, Lundin Prof Knut E A, Anisdahl Karoline, Syversen Silje Watterdal, Goll Guro Løvik, Lund-Johansen Fridtjof, Medhus Asle W, Jahnsen Prof Jørgen
Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway.
Department of Gastroenterology, Oslo University Hospital, Ullevål, Oslo, Norway.
Scand J Gastroenterol. 2023 Jul-Dec;58(8):874-882. doi: 10.1080/00365521.2023.2177884. Epub 2023 Feb 14.
Immune responses following SARS-CoV-2 vaccination in patients with inflammatory bowel disease (IBD) are not well characterized. The aims of this study were to explore the serological response associated with IBD, and immunosuppressive medications including serum concentrations of biologics and thiopurine metabolites.
This prospective, observational study included adult patients with ulcerative colitis (UC) and Crohn's disease (CD), and healthy controls. Antibodies to the receptor-binding domain of SARS-CoV-2 spike proteins, and serum concentrations of ongoing biologic and immunomodulatory medications were assessed prior to, and 2-5 weeks after the second vaccine dose. Serologic response was defined as anti-Spike antibodies ≥70 AU/ml.
In 958 IBD patients (380 UC, 578 CD) and 323 healthy controls, the median (Q Q) anti-Spike antibody level (AU/ml) was lower in patients (618 (192; 4370)) compared to controls (3355 (896; 7849)) ( < 0.001). The antibody levels were lower in CD (439 (174; 3304)) compared to UC (1088 (251; 5975)) ( < 0.001). No associations were demonstrated between antibody levels and serum drug concentrations for TNF inhibitor (TNFi), vedolizumab and ustekinumab. Patients receiving TNFi + thiopurines with a subtherapeutic 6-thioguanine nucleotide (6-TGN) level had higher response rate (93%) compared to patients with 6-TGN within the therapeutic range (53%) ( = 0.003). A diagnosis of UC, mRNA-1273 vaccine, and other treatments than TNFi + thiopurines were associated with humoral response.
Patients with CD had an attenuated humoral response to SARS-COV-2 vaccination as compared to patients with UC. The lack of association between serum levels of biologics and serologic response indicates vaccination regardless of proximity to drug administration.
炎症性肠病（IBD）患者接种新型冠状病毒2（SARS-CoV-2）疫苗后的免疫反应尚未得到充分表征。本研究的目的是探讨与IBD相关的血清学反应，以及免疫抑制药物，包括生物制剂和硫嘌呤代谢物的血清浓度。
这项前瞻性观察性研究纳入了成年溃疡性结肠炎（UC）和克罗恩病（CD）患者以及健康对照者。在第二次疫苗接种前和接种后2-5周评估针对SARS-CoV-2刺突蛋白受体结合域的抗体，以及正在使用的生物制剂和免疫调节药物的血清浓度。血清学反应定义为抗刺突抗体≥70 AU/ml。
在958例IBD患者（380例UC，578例CD）和323例健康对照者中，患者的抗刺突抗体水平中位数（四分位数间距）（AU/ml）为618（192；4370），低于对照者的3355（896；7849）（P<0.001）。CD患者的抗体水平（439（174；3304））低于UC患者的（1088（251；5975））（P<0.001）。未发现抗体水平与肿瘤坏死因子抑制剂（TNFi）、维多珠单抗和乌司奴单抗的血清药物浓度之间存在关联。与6-硫鸟嘌呤核苷酸（6-TGN）水平处于治疗范围内的患者（53%）相比，接受TNFi+硫嘌呤且6-TGN水平低于治疗水平的患者的反应率更高（93%）（P=0.003）。UC诊断、mRNA-1273疫苗以及TNFi+硫嘌呤以外的其他治疗与体液反应相关。
与UC患者相比，CD患者对SARS-CoV-2疫苗的体液反应减弱。生物制剂血清水平与血清学反应之间缺乏关联表明，无论是否临近给药时间均可进行疫苗接种。
