COVID-19 vaccine-induced antibody and T-cell responses in immunosuppressed patients with inflammatory bowel disease after the third vaccine dose (VIP): a multicentre, prospective, case-control study.
COVID-19 vaccine-induced antibody and T-cell responses in immunosuppressed patients with inflammatory bowel disease after the third vaccine dose (VIP): a multicentre, prospective, case-control study.
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DOI：
10.1016/s2468-1253(22)00274-6
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发表时间：
2022-11
影响因子：
35.7
通讯作者：
Powell, Nick
中科院分区：
文献类型：
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作者：
Alexander, James L.;Liu, Zhigang;Sandoval, Diana Munoz;Reynolds, Catherine;Ibraheim, Hajir;Anandabaskaran, Sulak;Saifuddin, Aamir;Seoane, Rocio Castro;Anand, Nikhil;Nice, Rachel;Bewshea, Claire;D'Mello, Andrea;Constable, Laura;Jones, Gareth R.;Balarajah, Sharmili;Fiorentino, Francesca;Sebastian, Shaji;Irving, Peter M.;Hicks, Lucy C.;Williams, Horace R. T.;Kent, Alexandra J.;Linger, Rachel;Parkes, Miles;Kok, Klaartje;Patel, Kamal V.;Teare, Julian P.;Altmann, Daniel M.;Goodhand, James R.;Hart, Ailsa L.;Lees, Charlie W.;Boyton, Rosemary J.;Kennedy, Nicholas A.;Ahmad, Tariq;Powell, Nick
炎症性肠病（IBD）患者在接种两剂疫苗后服用抗TNF或托法替尼后，COVID-19疫苗诱导的抗体应答降低。我们试图评估免疫抑制治疗是否与IBD患者在第三次疫苗接种后抗体和T细胞应答降低相关。VIP是一项在英国9个中心进行的多中心、前瞻性、病例对照研究。我们招募了免疫抑制的IBD患者和非免疫抑制的健康个体。所有参与者均年满18岁。健康对照组未诊断出IBD，目前未接受全身免疫抑制治疗以治疗任何其他适应症。免疫抑制的IBD患者具有克罗恩病、溃疡性结肠炎或使用IBD的标准定义的未分类IBD的确定诊断，并且在首次接种SARS-CoV-2疫苗时接受六种免疫抑制方案之一的确定治疗至少12周。所有参与者都必须接种三剂获批的COVID-19疫苗。在所有参与者组中测量SARS-CoV-2刺突抗体结合和T细胞应答。主要结果是第三次疫苗接种后28-49天的抗SARS-CoV-2刺突（S1受体结合域[RBD]）抗体浓度，根据年龄、同源与异源疫苗接种时间表和既往SARS-CoV-2感染进行调整。在所有有可用数据的参与者中评估主要结局。在2021年10月18日至2022年3月29日期间，352例受试者入选研究（硫嘌呤n=65，英夫利西单抗n=46，硫嘌呤+英夫利西单抗联合治疗n= 49，乌司奴单抗n=44，Vedolizumab n=50，托法替尼n=26，健康对照n=72）。在第三次接种疫苗后，所有组中抗SARS-CoV-2 S1 RBD抗体浓度的几何平均值均升高，但在接受英夫利西单抗治疗的患者中显著降低（2736·8 U/mL [几何SD 4·3]; p<0·0001），英夫利西单抗+硫嘌呤（1818·3 U/mL [6·7]; p<0·0001）和托法替尼（8071·5 U/mL [3·1]; p=0·0018）与健康对照组（16 774·2 U/mL [2·6]）相比。健康对照组与接受巯嘌呤（12 019·7 U/mL [2·2]; p=0·099）、优特克单抗（11 089·3 U/mL [2·8]; p =0·060）或Vedolizumab（13 564·9 U/mL [2·4]; p=0·27）治疗的患者之间的抗SARS-CoV-2 S1 RBD抗体浓度无显著差异。在多变量建模中，较低的抗SARS-CoV-2 S1 RBD抗体浓度与英夫利西单抗独立相关（几何均值比0.15 [95% CI 0.11 - 0.21]; p<0.0001），托法替尼（0·52 [CI 0·31-0·87]; p=0·012）和硫嘌呤（0·69 [0·51-0·95]; p=0·021），但与优特克单抗（0·64 [0·39-1·06]; p=0·083）或Vedolizumab（0·84 [0·54-1·30]; p=0·43）无关。既往SARS-CoV-2感染（1.58 [1.22 - 2.05]; p= 0.0006）与较高的抗SARS-CoV-2 S1 RBD抗体浓度独立相关，年龄较大（0.88 [0.80 - 0.97]; p= 0.0073）与较低的抗SARS-CoV-2 S1 RBD抗体浓度独立相关。抗原特异性T细胞应答在所有组中相似，除了没有既往感染证据的托法替尼接受者，其T细胞应答相对于健康对照显著降低（p=0·021）。第三剂COVID-19疫苗在免疫抑制的IBD患者中诱导了抗体结合的增强，但在服用英夫利西单抗、英夫利西单抗加硫嘌呤和托法替尼的患者中，这些反应降低。托法替尼也与T细胞应答降低相关。这些发现支持继续优先考虑免疫抑制组进一步疫苗加强给药，特别是使用抗TNF和JAK抑制剂的患者。辉瑞制药
COVID-19 vaccine-induced antibody responses are reduced in patients with inflammatory bowel disease (IBD) taking anti-TNF or tofacitinib after two vaccine doses. We sought to assess whether immunosuppressive treatments were associated with reduced antibody and T-cell responses in patients with IBD after a third vaccine dose. VIP was a multicentre, prospective, case-control study done in nine centres in the UK. We recruited immunosuppressed patients with IBD and non-immunosuppressed healthy individuals. All participants were aged 18 years or older. The healthy control group had no diagnosis of IBD and no current treatment with systemic immunosuppressive therapy for any other indication. The immunosuppressed patients with IBD had an established diagnosis of Crohn's disease, ulcerative colitis, or unclassified IBD using standard definitions of IBD, and were receiving established treatment with one of six immunosuppressive regimens for at least 12 weeks at the time of first dose of SARS-CoV-2 vaccination. All participants had to have received three doses of an approved COVID-19 vaccine. SARS-CoV-2 spike antibody binding and T-cell responses were measured in all participant groups. The primary outcome was anti-SARS-CoV-2 spike (S1 receptor binding domain [RBD]) antibody concentration 28–49 days after the third vaccine dose, adjusted by age, homologous versus heterologous vaccine schedule, and previous SARS-CoV-2 infection. The primary outcome was assessed in all participants with available data. Between Oct 18, 2021, and March 29, 2022, 352 participants were included in the study (thiopurine n=65, infliximab n=46, thiopurine plus infliximab combination therapy n=49, ustekinumab n=44, vedolizumab n=50, tofacitinib n=26, and healthy controls n=72). Geometric mean anti-SARS-CoV-2 S1 RBD antibody concentrations increased in all groups following a third vaccine dose, but were significantly lower in patients treated with infliximab (2736·8 U/mL [geometric SD 4·3]; p<0·0001), infliximab plus thiopurine (1818·3 U/mL [6·7]; p<0·0001), and tofacitinib (8071·5 U/mL [3·1]; p=0·0018) compared with the healthy control group (16 774·2 U/mL [2·6]). There were no significant differences in anti-SARS-CoV-2 S1 RBD antibody concentrations between the healthy control group and patients treated with thiopurine (12 019·7 U/mL [2·2]; p=0·099), ustekinumab (11 089·3 U/mL [2·8]; p=0·060), or vedolizumab (13 564·9 U/mL [2·4]; p=0·27). In multivariable modelling, lower anti-SARS-CoV-2 S1 RBD antibody concentrations were independently associated with infliximab (geometric mean ratio 0·15 [95% CI 0·11–0·21]; p<0·0001), tofacitinib (0·52 [CI 0·31–0·87]; p=0·012), and thiopurine (0·69 [0·51–0·95]; p=0·021), but not with ustekinumab (0·64 [0·39–1·06]; p=0·083), or vedolizumab (0·84 [0·54–1·30]; p=0·43). Previous SARS-CoV-2 infection (1·58 [1·22–2·05]; p=0·0006) was independently associated with higher anti-SARS-CoV-2 S1 RBD antibody concentrations and older age (0·88 [0·80–0·97]; p=0·0073) was independently associated with lower anti-SARS-CoV-2 S1 RBD antibody concentrations. Antigen-specific T-cell responses were similar in all groups, except for recipients of tofacitinib without evidence of previous infection, where T-cell responses were significantly reduced relative to healthy controls (p=0·021). A third dose of COVID-19 vaccine induced a boost in antibody binding in immunosuppressed patients with IBD, but these responses were reduced in patients taking infliximab, infliximab plus thiopurine, and tofacitinib. Tofacitinib was also associated with reduced T-cell responses. These findings support continued prioritisation of immunosuppressed groups for further vaccine booster dosing, particularly patients on anti-TNF and JAK inhibitors. Pfizer.