Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK; Department of Gastroenterology, Imperial College Healthcare NHS Trust, London, UK.
Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
Lancet Gastroenterol Hepatol. 2022 Nov;7(11):1005-1015. doi: 10.1016/S2468-1253(22)00274-6. Epub 2022 Sep 9.
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.
COVID-19 疫苗接种后，接受抗 TNF 或托法替尼治疗的炎症性肠病（IBD）患者的抗体反应会降低。我们试图评估在接受第三剂疫苗后，IBD 患者的免疫抑制治疗是否与抗体和 T 细胞反应降低有关。
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。所有参与者年龄均在 18 岁及以上。健康对照组没有 IBD 诊断，也没有因其他任何原因接受全身免疫抑制治疗。免疫抑制的 IBD 患者采用 IBD 的标准定义确诊为克罗恩病、溃疡性结肠炎或未分类的 IBD，并且在接受 SARS-CoV-2 疫苗接种第一剂时至少接受了 12 周的一种或六种免疫抑制方案的既定治疗。所有参与者都必须接受过三剂批准的 COVID-19 疫苗。在所有参与者中测量了 SARS-CoV-2 刺突抗体结合和 T 细胞反应。主要结局是第三剂疫苗接种后 28-49 天的抗 SARS-CoV-2 刺突（S1 受体结合域[RBD]）抗体浓度，通过年龄、同源或异源疫苗方案以及以前的 SARS-CoV-2 感染进行调整。所有有可用数据的参与者都评估了主要结局。
在 2021 年 10 月 18 日至 2022 年 3 月 29 日期间，352 名参与者被纳入研究（硫唑嘌呤 n=65、英夫利昔单抗 n=46、硫唑嘌呤联合英夫利昔单抗联合治疗 n=49、乌司奴单抗 n=44、vedolizumab n=50、托法替尼 n=26 和健康对照组 n=72）。在接受第三剂疫苗后，所有组的 SARS-CoV-2 S1 RBD 抗体浓度均有所增加，但接受英夫利昔单抗（2736·8 U/mL [几何标准差 4·3]；p<0·0001）、英夫利昔单抗加硫唑嘌呤（1818·3 U/mL [6·7]；p<0·0001）和托法替尼（8071·5 U/mL [3·1]；p=0·0018）治疗的患者的 SARS-CoV-2 S1 RBD 抗体浓度明显低于健康对照组（16774·2 U/mL [2·6]）。健康对照组与接受硫唑嘌呤（12019·7 U/mL [2·2]；p=0·099）、乌司奴单抗（11089·3 U/mL [2·8]；p=0·060）或 vedolizumab（13564·9 U/mL [2·4]；p=0·27）治疗的患者之间的 SARS-CoV-2 S1 RBD 抗体浓度没有显著差异。在多变量模型中，较低的 SARS-CoV-2 S1 RBD 抗体浓度与英夫利昔单抗（几何平均比 0·15 [95%CI 0·11-0·21]；p<0·0001）、托法替尼（0·52 [0·31-0·87]；p=0·012）和硫唑嘌呤（0·69 [0·51-0·95]；p=0·021）独立相关，但与乌司奴单抗（0·64 [0·39-1·06]；p=0·083）或 vedolizumab（0·84 [0·54-1·30]；p=0·43）无关。先前的 SARS-CoV-2 感染（1·58 [1·22-2·05]；p=0·0006）与较高的 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 SARS-CoV-2 S1 RBD 抗体浓度独立相关。除了未感染的托法替尼治疗者外，所有组的抗原特异性 T 细胞反应均相似，而未感染的托法替尼治疗者的 T 细胞反应明显低于健康对照组（p=0·021）。
COVID-19 疫苗接种第三剂可诱导免疫抑制的 IBD 患者抗体结合增强，但接受英夫利昔单抗、英夫利昔单抗加硫唑嘌呤和托法替尼治疗的患者的抗体反应降低。托法替尼也与降低的 T 细胞反应相关。这些发现支持继续为免疫抑制人群优先考虑进一步的疫苗加强剂量，特别是抗 TNF 和 JAK 抑制剂治疗的患者。
辉瑞。
