Abstract：
OBJECTIVE: To study the effect of mycophenolate mofetil (MMF) on various vaccination responses in kidney transplant recipients.
METHODS: In a randomized controlled trial (EudraCT nr.: 2014-001372-66), low immunologically risk kidney transplant recipients were randomized to TAC/MMF or TAC-monotherapy (TACmono), six months post-transplantation. One year after transplantation, in a pre-specified sub-study, recipients were vaccinated against pneumococcus, tetanus and influenza. Blood was sampled before and 21 days after vaccination. Adequate vaccination responses were defined by international criteria. A post-hoc analysis was conducted on SARS-CoV-2 vaccination responses within the same cohort.
RESULTS: Seventy-one recipients received pneumococcal and tetanus vaccines (TAC/MMF: n = 37, TACmono: n = 34), with 29 also vaccinated against influenza. When vaccinated, recipients were 60 (54-66) years old, with median eGFR of 54 (44-67) ml/min, tacrolimus trough levels 6.1 (5.4-7.0) ug/L in both groups and TAC/MMF daily MMF dose of 1000 (500-2000) mg. Adequate vaccination responses were: pneumococcal (TAC/MMF 43%, TACmono 74%, p = 0.016), tetanus (TAC/MMF 35%, TACmono 82%, p < 0.0001) and influenza (TAC/MMF 20%, TACmono 71%, p = 0.0092). Only 7% of TAC/MMF responded adequately to all three compared to 36% of TACmono (p = 0.080). Additionally, 40% of TAC/MMF responded inadequately to all three, whereas all TACmono patients responded adequately to at least one vaccination (p = 0.041). Lower SARS-CoV-2 vaccination antibody responses correlated with lower pneumococcal antibody vaccination responses (correlation coefficient: 0.41, p = 0.040).
CONCLUSIONS: MMF on top of tacrolimus severely hampers antibody responses to a broad range of vaccinations.
METHODS: In a randomized controlled trial (EudraCT nr.: 2014-001372-66), low immunologically risk kidney transplant recipients were randomized to TAC/MMF or TAC-monotherapy (TACmono), six months post-transplantation. One year after transplantation, in a pre-specified sub-study, recipients were vaccinated against pneumococcus, tetanus and influenza. Blood was sampled before and 21 days after vaccination. Adequate vaccination responses were defined by international criteria. A post-hoc analysis was conducted on SARS-CoV-2 vaccination responses within the same cohort.
RESULTS: Seventy-one recipients received pneumococcal and tetanus vaccines (TAC/MMF: n = 37, TACmono: n = 34), with 29 also vaccinated against influenza. When vaccinated, recipients were 60 (54-66) years old, with median eGFR of 54 (44-67) ml/min, tacrolimus trough levels 6.1 (5.4-7.0) ug/L in both groups and TAC/MMF daily MMF dose of 1000 (500-2000) mg. Adequate vaccination responses were: pneumococcal (TAC/MMF 43%, TACmono 74%, p = 0.016), tetanus (TAC/MMF 35%, TACmono 82%, p < 0.0001) and influenza (TAC/MMF 20%, TACmono 71%, p = 0.0092). Only 7% of TAC/MMF responded adequately to all three compared to 36% of TACmono (p = 0.080). Additionally, 40% of TAC/MMF responded inadequately to all three, whereas all TACmono patients responded adequately to at least one vaccination (p = 0.041). Lower SARS-CoV-2 vaccination antibody responses correlated with lower pneumococcal antibody vaccination responses (correlation coefficient: 0.41, p = 0.040).
CONCLUSIONS: MMF on top of tacrolimus severely hampers antibody responses to a broad range of vaccinations.
摘要：
目的：研究霉酚酸酯（MMF）对肾移植受者各种疫苗接种反应的影响。
方法：在一项随机对照试验中（EudraCTnr。：2014-001372-66），低免疫风险肾移植受者随机接受TAC/MMF或TAC单一疗法（TACmono），移植后六个月.移植一年后,在预先指定的子研究中，接受者接种了肺炎球菌疫苗，破伤风和流感。在疫苗接种前和接种后21天取样血液。适当的疫苗接种反应由国际标准定义。对同一队列中的SARS-CoV-2疫苗接种反应进行事后分析。
结果：71名接受者接受了肺炎球菌和破伤风疫苗（TAC/MMF：n=37，TACmono：n=34），29人也接种了流感疫苗。接种疫苗时，收件人60（54-66）岁，eGFR中位数为54（44-67）ml/min，两组他克莫司谷水平为6.1（5.4-7.0）ug/L，TAC/MMF日MMF剂量为1000（500-2000）mg。足够的疫苗接种反应是：肺炎球菌(TAC/MMF43%，TACmono74%,p=0.016),破伤风（TAC/MMF35%，TACmono82%,p<0.0001)和流感(TAC/MMF20%，TACmono71%,p=0.0092)。与36％的TACmono相比，只有7％的TAC/MMF对所有三个都有足够的反应（p=0.080）。此外,40%的TAC/MMF对这三者反应不充分，而所有TACmono患者对至少一次疫苗接种反应充分(p=0.041).较低的SARS-CoV-2疫苗接种抗体应答与较低的肺炎球菌抗体疫苗接种应答相关(相关系数:0.41,p=0.040)。
结论：在他克莫司之上的MMF严重阻碍了广泛疫苗接种的抗体反应。
方法：在一项随机对照试验中（EudraCTnr。：2014-001372-66），低免疫风险肾移植受者随机接受TAC/MMF或TAC单一疗法（TACmono），移植后六个月.移植一年后,在预先指定的子研究中，接受者接种了肺炎球菌疫苗，破伤风和流感。在疫苗接种前和接种后21天取样血液。适当的疫苗接种反应由国际标准定义。对同一队列中的SARS-CoV-2疫苗接种反应进行事后分析。
结果：71名接受者接受了肺炎球菌和破伤风疫苗（TAC/MMF：n=37，TACmono：n=34），29人也接种了流感疫苗。接种疫苗时，收件人60（54-66）岁，eGFR中位数为54（44-67）ml/min，两组他克莫司谷水平为6.1（5.4-7.0）ug/L，TAC/MMF日MMF剂量为1000（500-2000）mg。足够的疫苗接种反应是：肺炎球菌(TAC/MMF43%，TACmono74%,p=0.016),破伤风（TAC/MMF35%，TACmono82%,p<0.0001)和流感(TAC/MMF20%，TACmono71%,p=0.0092)。与36％的TACmono相比，只有7％的TAC/MMF对所有三个都有足够的反应（p=0.080）。此外,40%的TAC/MMF对这三者反应不充分，而所有TACmono患者对至少一次疫苗接种反应充分(p=0.041).较低的SARS-CoV-2疫苗接种抗体应答与较低的肺炎球菌抗体疫苗接种应答相关(相关系数:0.41,p=0.040)。
结论：在他克莫司之上的MMF严重阻碍了广泛疫苗接种的抗体反应。
