英夫利昔单抗与 IBD 患者对 BNT162b2 和 ChAdOx1 nCoV-19 SARS-CoV-2 疫苗的免疫原性降低有关。

Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines in patients with IBD.

机构信息

Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.

Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK.

出版信息

Gut. 2021 Oct;70(10):1884-1893. doi: 10.1136/gutjnl-2021-324789. Epub 2021 Apr 26.

DOI:10.1136/gutjnl-2021-324789

PMID:33903149

Abstract

OBJECTIVE

Delayed second dose SARS-CoV-2 vaccination trades maximal effectiveness for a lower level of immunity across more of the population. We investigated whether patients with inflammatory bowel disease treated with infliximab have attenuated serological responses to a single dose of a SARS-CoV-2 vaccine.

DESIGN

Antibody responses and seroconversion rates in infliximab-treated patients (n=865) were compared with a cohort treated with vedolizumab (n=428), a gut-selective anti-integrin α4β7 monoclonal antibody. Our primary outcome was anti-SARS-CoV-2 spike (S) antibody concentrations, measured using the Elecsys anti-SARS-CoV-2 spike (S) antibody assay 3-10 weeks after vaccination, in patients without evidence of prior infection. Secondary outcomes were seroconversion rates (defined by a cut-off of 15 U/mL), and antibody responses following past infection or a second dose of the BNT162b2 vaccine.

RESULTS

Geometric mean (SD) anti-SARS-CoV-2 antibody concentrations were lower in patients treated with infliximab than vedolizumab, following BNT162b2 (6.0 U/mL (5.9) vs 28.8 U/mL (5.4) p<0.0001) and ChAdOx1 nCoV-19 (4.7 U/mL (4.9)) vs 13.8 U/mL (5.9) p<0.0001) vaccines. In our multivariable models, antibody concentrations were lower in infliximab-treated compared with vedolizumab-treated patients who received the BNT162b2 (fold change (FC) 0.29 (95% CI 0.21 to 0.40), p<0.0001) and ChAdOx1 nCoV-19 (FC 0.39 (95% CI 0.30 to 0.51), p<0.0001) vaccines. In both models, age ≥60 years, immunomodulator use, Crohn's disease and smoking were associated with lower, while non-white ethnicity was associated with higher, anti-SARS-CoV-2 antibody concentrations. Seroconversion rates after a single dose of either vaccine were higher in patients with prior SARS-CoV-2 infection and after two doses of BNT162b2 vaccine.

CONCLUSION

Infliximab is associated with attenuated immunogenicity to a single dose of the BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines. Vaccination after SARS-CoV-2 infection, or a second dose of vaccine, led to seroconversion in most patients. Delayed second dosing should be avoided in patients treated with infliximab.

TRIAL REGISTRATION NUMBER

ISRCTN45176516.

摘要

目的

延迟接种第二剂 SARS-CoV-2 疫苗会降低人群对病毒的免疫水平，但能提高疫苗的最大有效性。我们研究了接受英夫利昔单抗治疗的炎症性肠病患者对 SARS-CoV-2 疫苗单剂接种的血清学反应是否减弱。

设计

比较了接受英夫利昔单抗治疗的患者（n=865）与接受维得利珠单抗（n=428）治疗的患者的抗体应答和血清转化率。维得利珠单抗是一种肠道选择性抗整合素 α4β7 单克隆抗体。我们的主要结局是无既往感染证据的患者在接种疫苗后 3-10 周时，用 Elecsys SARS-CoV-2 刺突（S）抗体测定法测量抗 SARS-CoV-2 刺突（S）抗体浓度。次要结局是血清转化率（定义为 15U/ml 为界值）和既往感染或第二剂 BNT162b2 疫苗后的抗体应答。

结果

与接受维得利珠单抗治疗的患者相比，接受英夫利昔单抗治疗的患者在接种 BNT162b2 （6.0U/ml（5.9）比 28.8U/ml（5.4），p<0.0001）和 ChAdOx1 nCoV-19 （4.7U/ml（4.9））疫苗后，抗 SARS-CoV-2 抗体浓度较低。在我们的多变量模型中，与接受维得利珠单抗治疗的患者相比，接受英夫利昔单抗治疗的患者接种 BNT162b2（FC 0.29（95%CI 0.21 至 0.40），p<0.0001）和 ChAdOx1 nCoV-19 （FC 0.39（95%CI 0.30 至 0.51），p<0.0001）疫苗的抗体浓度较低。在这两种模型中，年龄≥60 岁、免疫调节剂的使用、克罗恩病和吸烟与较低的 SARS-CoV-2 抗体浓度相关，而非白种人则与较高的 SARS-CoV-2 抗体浓度相关。在有既往 SARS-CoV-2 感染史的患者和接受两剂 BNT162b2 疫苗接种后，两种疫苗单剂接种后的血清转化率均较高。在接受英夫利昔单抗治疗的患者中，应避免延迟接种第二剂疫苗。