COVID-19 vaccine-induced antibody responses in immunosuppressed patients with inflammatory bowel disease (VIP): a multicentre, prospective, case-control study.
COVID-19 vaccine-induced antibody responses in immunosuppressed patients with inflammatory bowel disease (VIP): a multicentre, prospective, case-control study.
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DOI：
10.1016/s2468-1253(22)00005-x
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发表时间：
2022-04
期刊：
影响因子：
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通讯作者：
VIP study investigators
中科院分区：
文献类型：
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作者：
Alexander JL;Kennedy NA;Ibraheim H;Anandabaskaran S;Saifuddin A;Castro Seoane R;Liu Z;Nice R;Bewshea C;D'Mello A;Constable L;Jones GR;Balarajah S;Fiorentino F;Sebastian S;Irving PM;Hicks LC;Williams HRT;Kent AJ;Linger R;Parkes M;Kok K;Patel KV;Teare JP;Altmann DM;Boyton RJ;Goodhand JR;Hart AL;Lees CW;Ahmad T;Powell N;VIP study investigators
炎症性肠病（IBD）的治疗对新型冠状病毒肺炎（COVID - 19）疫苗免疫应答的影响尚未完全明确。因此，我们试图确定在使用常用免疫抑制药物的IBD患者中，COVID - 19疫苗诱导的抗体应答是否发生改变。
在这项多中心、前瞻性病例对照研究（VIP）中，我们从英国9个中心招募了接受6种不同免疫抑制治疗方案（硫嘌呤类、英夫利昔单抗、硫嘌呤类加英夫利昔单抗、乌司奴单抗、维得利珠单抗或托法替布）之一治疗的IBD成人患者以及健康对照参与者。符合条件的参与者年龄为18岁及以上，且间隔6 - 12周接种了两剂COVID - 19疫苗（ChAdOx1 nCoV - 19[牛津 - 阿斯利康]、BNT162b2[辉瑞 - 生物新技术公司]或mRNA1273[莫德纳]）（根据英国采用的接种计划）。我们在第二剂疫苗接种后53 - 92天使用罗氏Elecsys抗新型冠状病毒刺突蛋白电化学发光免疫分析法检测抗体应答。主要结局是既往无新型冠状病毒感染的参与者中抗新型冠状病毒刺突蛋白抗体浓度，经年龄和疫苗类型调整，并使用多变量线性回归模型进行分析。本研究在国际标准随机对照试验编号注册库（ISRCTN Registry）注册，编号为ISRCTN13495664，且正在进行中。
2021年5月31日至11月24日期间，我们招募了483名参与者，包括接受硫嘌呤类（n = 78）、英夫利昔单抗（n = 63）、硫嘌呤类加英夫利昔单抗（n = 72）、乌司奴单抗（n = 57）、维得利珠单抗（n = 62）或托法替布（n = 30）治疗的IBD患者以及121名健康对照者。在主要分析中，我们纳入了370名无既往感染证据的参与者。与对照组（1578.3 U/mL[几何标准差3.7]）相比，接受英夫利昔单抗（156.8 U/mL[几何标准差5.7]；p < 0.0001）、英夫利昔单抗加硫嘌呤类（111.1 U/mL[5.7]；p < 0.0001）或托法替布（429.5 U/mL[3.1]；p = 0.0012）治疗的患者抗新型冠状病毒刺突蛋白抗体几何平均浓度显著降低。接受硫嘌呤类单药治疗（1019.8 U/mL[4.3]；p = 0.74）、乌司奴单抗（582.4 U/mL[4.6]；p = 0.11）或维得利珠单抗（954.0 U/mL[4.1]；p = 0.50）的患者与健康对照组之间抗体浓度无显著差异。在多变量模型中，较低的抗新型冠状病毒刺突蛋白抗体浓度与英夫利昔单抗（几何均数比0.12，95%置信区间0.08 - 0.17；p < 0.0001）和托法替布（0.43，0.23 - 0.81；p = 0.0095）独立相关，但与乌司奴单抗（0.69，0.41 - 1.19；p = 0.18）、硫嘌呤类（0.89，0.64 - 1.24；p = 0.50）或维得利珠单抗（1.16，0.74 - 1.83；p = 0.51）无关。mRNA疫苗（3.68，2.80 - 4.84；p < 0.0001；与腺病毒载体疫苗相比）与较高的抗体浓度独立相关，而年龄每增加10岁（0.79，0.72 - 0.87；p < 0.0001）与较低的抗体浓度相关。
对于IBD患者，COVID - 19疫苗的免疫原性因免疫抑制药物暴露情况而异，在英夫利昔单抗、英夫利昔单抗加硫嘌呤类以及托法替布的使用者中减弱。第三剂基础针或加强针的接种时间安排可根据个体治疗情况进行个性化调整，服用抗肿瘤坏死因子药物和托法替布的患者应优先考虑。
辉瑞（最后一个单词“Pfizer”可能是原文中遗留的品牌名称相关信息，在中文语境下可根据实际情况灵活处理，如果是强调研究与辉瑞相关，可适当补充说明，如果只是原文的一个标识，可不做过多处理，此处保留英文原文供参考）
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.