Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK.
Gut. 2021 Oct;70(10):1884-1893. doi: 10.1136/gutjnl-2021-324789. Epub 2021 Apr 26.
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.
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.
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.
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.
ISRCTN45176516.
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。
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。
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。
ISRCTN45176516。
