炎性肠病(IBD)疗法对SARS-CoV-2疫苗接种的免疫应答的影响尚未完全知道。因此,我们试图确定IBD患者使用常用免疫抑制药物后,COVID-19疫苗诱导的抗体应答是否发生改变.
在这个多中心,prospective,病例对照研究(VIP),我们招募了使用六种不同免疫抑制治疗方案之一治疗的IBD成人(硫代嘌呤,英夫利昔单抗,硫嘌呤加英夫利昔单抗,ustekinumab,维多珠单抗,或托法替尼)和来自英国9个中心的健康对照参与者。符合条件的参与者年龄在18岁或以上,并接受了两剂COVID-19疫苗(ChAdOx1nCoV-19[牛津阿斯利康],BNT162b2[辉瑞-BioNTech],或mRNA1273[Moderna])间隔6-12周(根据英国采用的时间表)。我们使用RocheElecsys抗SARS-CoV-2尖峰电化学发光免疫测定法测量了第二次疫苗剂量后53-92天的抗体反应。主要结果是先前没有SARS-CoV-2感染的参与者的抗SARS-CoV-2尖峰蛋白抗体浓度,按年龄和疫苗类型调整,并采用多元线性回归模型进行分析。这项研究在ISRCTN注册中心注册,ISRCTN13495664,并正在进行中。
2021年5月31日至11月24日,我们招募了483名参与者,包括正在接受硫嘌呤治疗的IBD患者(n=78),英夫利昔单抗(n=63),硫嘌呤加英夫利昔单抗(n=72),ustekinumab(n=57),维多珠单抗(n=62),或托法替尼(n=30),和121个健康对照。在我们的初步分析中,我们纳入了370名没有先前感染证据的参与者。英夫利昔单抗治疗的患者的几何平均抗SARS-CoV-2刺突蛋白抗体浓度显着降低(156·8U/mL[几何SD5·7];p<0·0001),英夫利昔单抗加硫嘌呤(111·1U/mL[5·7];p<0·0001),或托法替尼(429·5U/mL[3·1];p=0·0012)与对照组(1578·3U/mL[3·7])相比。用硫嘌呤单药治疗的患者之间的抗体浓度没有显着差异(1019·8U/mL[4·3];p=0·74),ustekinumab(582·4U/mL[4·6];p=0·11),或维多珠单抗(954·0U/mL[4·1];p=0·50)和健康对照。在多变量建模中,较低的抗SARS-CoV-2刺突蛋白抗体浓度与英夫利昔单抗(几何平均比0·12,95%CI0·08-0·17;p<0·0001)和托法替尼(0·43,0·23-0·81;p=0·0095)独立相关,但不使用ustekinumab(0·69,0·41-1·19;p=0·18),硫代嘌呤(0·89,0·64-1·24;p=0·50),或维多珠单抗(1·16,0·74-1·83;p=0·51)。mRNA疫苗(3·68,2·80-4·84;p<0·0001;与腺病毒载体疫苗相比)与较高的抗体浓度和较低的每十年年龄(0·79,0·72-0·87;p<0·0001)独立相关。
对于IBD患者,COVID-19疫苗的免疫原性因免疫抑制药物暴露而异,并在英夫利昔单抗的接受者体内减毒,英夫利昔单抗加硫嘌呤,和托法替尼。第三小学的日程安排,或助推器,剂量可以根据个人的治疗个性化,应优先考虑服用抗肿瘤坏死因子和托法替尼的患者.
辉瑞。
The effects that therapies for inflammatory bowel disease (IBD) have on immune responses to SARS-CoV-2 vaccination are not yet fully known. Therefore, we sought to determine whether COVID-19 vaccine-induced antibody responses were altered in patients with IBD on commonly used immunosuppressive drugs.
In this multicentre, prospective,
case-control study (VIP), we recruited adults with IBD treated with one of six different immunosuppressive treatment regimens (thiopurines, infliximab, a thiopurine plus infliximab, ustekinumab, vedolizumab, or tofacitinib) and healthy control participants from nine centres in the UK. Eligible participants were aged 18 years or older and had received two doses of COVID-19 vaccines (either ChAdOx1 nCoV-19 [Oxford-AstraZeneca], BNT162b2 [Pfizer-BioNTech], or mRNA1273 [Moderna]) 6-12 weeks apart (according to scheduling adopted in the UK). We measured antibody responses 53-92 days after a second vaccine dose using the Roche Elecsys Anti-SARS-CoV-2 spike electrochemiluminescence immunoassay. The primary outcome was anti-SARS-CoV-2 spike protein antibody concentrations in participants without previous SARS-CoV-2 infection, adjusted by age and vaccine type, and was analysed by use of multivariable linear regression models. This study is registered in the ISRCTN Registry, ISRCTN13495664, and is ongoing.
Between May 31 and Nov 24, 2021, we recruited 483 participants, including patients with IBD being treated with thiopurines (n=78), infliximab (n=63), a thiopurine plus infliximab (n=72), ustekinumab (n=57), vedolizumab (n=62), or tofacitinib (n=30), and 121 healthy controls. We included 370 participants without evidence of previous infection in our primary analysis. Geometric mean anti-SARS-CoV-2 spike protein antibody concentrations were significantly lower in patients treated with infliximab (156·8 U/mL [geometric SD 5·7]; p<0·0001), infliximab plus thiopurine (111·1 U/mL [5·7]; p<0·0001), or tofacitinib (429·5 U/mL [3·1]; p=0·0012) compared with controls (1578·3 U/mL [3·7]). There were no significant differences in antibody concentrations between patients treated with thiopurine monotherapy (1019·8 U/mL [4·3]; p=0·74), ustekinumab (582·4 U/mL [4·6]; p=0·11), or vedolizumab (954·0 U/mL [4·1]; p=0·50) and healthy controls. In multivariable modelling, lower anti-SARS-CoV-2 spike protein antibody concentrations were independently associated with infliximab (geometric mean ratio 0·12, 95% CI 0·08-0·17; p<0·0001) and tofacitinib (0·43, 0·23-0·81; p=0·0095), but not with ustekinumab (0·69, 0·41-1·19; p=0·18), thiopurines (0·89, 0·64-1·24; p=0·50), or vedolizumab (1·16, 0·74-1·83; p=0·51). mRNA vaccines (3·68, 2·80-4·84; p<0·0001; vs adenovirus vector vaccines) were independently associated with higher antibody concentrations and older age per decade (0·79, 0·72-0·87; p<0·0001) with lower antibody concentrations.
For patients with IBD, the immunogenicity of COVID-19 vaccines varies according to immunosuppressive drug exposure, and is attenuated in recipients of infliximab, infliximab plus thiopurines, and tofacitinib. Scheduling of third primary, or booster, doses could be personalised on the basis of an individual\'s treatment, and patients taking anti-tumour necrosis factor and tofacitinib should be prioritised.
Pfizer.