The effect of immunomodulators on seroconversion after BNT162b2 and AZD1222 vaccines in patients with immune-mediated inflammatory diseases: a prospective cohort study.
The effect of immunomodulators on seroconversion after BNT162b2 and AZD1222 vaccines in patients with immune-mediated inflammatory diseases: a prospective cohort study.
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免疫调节剂对免疫介导的炎症性疾病患者接种 BNT162b2 和 AZD1222 疫苗后血清转化的影响：一项前瞻性队列研究。
DOI：
10.1093/bjd/ljac109
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Al-Janabi A
中科院分区：
文献类型：
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作者：
Al-Janabi A
背景生物和非生物免疫调节剂，用于治疗免疫介导的炎症性疾病（IMID），可能会削弱对COVID-19疫苗的免疫应答，从而影响疫苗的有效性。目的我们的目的是研究生物和非生物免疫调节剂与第一剂和第二剂COVID-19疫苗后血清转换之间的关系。方法在第一次或第二次接种BNT 162 b2或AZD 1222疫苗后，从接受生物和/或免疫治疗的患者中收集血清样品。或用于银屑病、银屑病关节炎、类风湿性关节炎、炎性肠病或系统性红斑狼疮中的一种或多种的非生物免疫调节剂。血清转化定义为Roche Elecsys®抗SARS-CoV-2 S（刺突蛋白亚基S1/受体结合域）免疫测定阳性（≥ 0.8 U mL-）。 免疫调节剂暴露和血清转换之间的关联进行了评估，使用逻辑回归，调整年龄和sex.ResultsAfter排除那些与先前的COVID-19，后第一次接种疫苗的样本从193名参与者和后第二次接种样本从312名参与者被纳入分析。第一剂疫苗接种后，17.6%（n= 34）的参与者未发生血清转化。与生物制剂单药治疗相比，非生物制剂[校正比值比（OR）0.29，95%置信区间（CI）0.12-0.69]或非生物制剂和生物制剂联合治疗（校正OR 0.14，95% CI 0.045-0.45）的血清转化率降低。亚组分析显示，与肿瘤坏死因子-α抑制剂单药治疗相比，接受甲氨蝶呤（校正OR 0.097，95% CI 0.19-0.49）或泼尼松龙治疗（校正OR 0.044，95% CI 0.002-1.00）的患者血清转换几率降低。接受利妥昔单抗的参与者（n< 5）在第一次疫苗剂量后没有血清转化。在第二剂疫苗接种后，所有参与者中有1.6%未发生血清转化。与接受其他治疗的患者相比，接受利妥昔单抗治疗的患者（n= 3/4）未发生血清转换（n= 2/308，P< 0.001）。事后分析表明，非血清转化与年龄[调整OR 0.18，95%CI 0.037-0.93，为那些年龄在60岁及以上（参考类别年龄18-39岁）]，但不性别，种族或疫苗type.ConclusionsTreatment与非生物制剂，特别是甲氨蝶呤，是与受损的血清转化后，两个BNT 162 b2或AZD 1222疫苗剂量，在IMID患者。 这些发现与其他已发表的研究结果一致。虽然这可能表明对COVID-19的保护作用降低，但需要确定与疫苗有效性最密切相关的免疫学参数才能得出这一结论。
BackgroundBiologic and nonbiologic immunomodulators, used to treat immune-mediated inflammatory diseases (IMIDs), could impair the immune response to COVID-19 vaccines and thus vaccine effectiveness.ObjectivesOur objective was to investigate the association between biologic and nonbiologic immunomodulators and seroconversion following the first and second dose of COVID-19 vaccines in patients with IMIDs.MethodsSerum samples were collected following the first or second dose of the BNT162b2 or AZD1222 vaccines from patients receiving biologic and/or nonbiologic immunomodulators for one or more of psoriasis, psoriatic arthritis, rheumatoid arthritis, inflammatory bowel disease or systemic lupus erythematosus. Seroconversion was defined as a positive Roche Elecsys® Anti-SARS-CoV-2 S (spike protein subunit S1/receptor binding domain) immunoassay (≥ 0.8 U mL–). Association between immunomodulator exposure and seroconversion was assessed using logistic regression, adjusting for age and sex.ResultsAfter excluding those with prior COVID-19, post-first vaccine dose samples from 193 participants and post-second dose samples from 312 participants were included in the analysis. Following the first vaccine dose, 17.6% (n= 34) of participants did not seroconvert. Seroconversion was reduced for those on nonbiologic [adjusted odds ratio (OR) 0.29, 95% confidence interval (CI) 0.12–0.69] or combined nonbiologic and biologic treatment (adjusted OR 0.14, 95% CI 0.045–0.45) compared with those on biologic monotherapy. Subgroup analysis demonstrated reduced odds of seroconversion in those on methotrexate (adjusted OR 0.097, 95% CI 0.19–0.49) or prednisolone treatment (adjusted OR 0.044, 95% CI 0.002–1.00) relative to tumour necrosis factor-α inhibitor monotherapy. No participants receiving rituximab (n< 5) seroconverted after the first vaccine dose. Following the second vaccine dose, 1.6% of all participants did not seroconvert. Non-seroconversion was associated with receiving rituximab (n= 3 of 4) compared with those receiving other therapies (n= 2 of 308,P< 0.001). Post hoc analyses demonstrated that non-seroconversion was associated with age [adjusted OR 0.18, 95% CI 0.037–0.93 for those aged 60 years and over (reference category age 18–39 years)], but not sex, ethnicity or vaccine type.ConclusionsTreatment with nonbiologics, particularly methotrexate, is associated with impaired seroconversion following two BNT162b2 or AZD1222 vaccine doses, in patients with IMIDs. These findings are consistent with those of other published studies. While this could indicate reduced protection against COVID-19, the immunological parameters that correlate most closely with vaccine effectiveness need to be defined to reach this conclusion.