Corinne Dickinson Goldsmith Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, 5 E 98th Street, New York, NY 10029, USA.
Corinne Dickinson Goldsmith Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, 5 E 98th Street, New York, NY 10029, USA.
Mult Scler Relat Disord. 2022 Jun;62:103737. doi: 10.1016/j.msard.2022.103737. Epub 2022 Mar 12.
Prior studies suggest reduced humoral response to COVID-19 vaccination in immunosuppressed populations. Disease modifying therapies (DMTs) for multiple sclerosis (MS) have variable immunomodulatory effects, and limited data are available for all DMTs. We aimed to determine the impact of DMTs on antibody response to COVID-19 vaccination among MS patients.
Patients with documented COVID-19 vaccination dates and anti-spike antibody results post-vaccination were identified between March-August 2021. Clinical data were retrospectively abstracted from chart review. Deidentified data were analyzed to evaluate antibody response, and multivariable logistic regression analyses were used to identify clinical and demographic predictors of antibody response. Data analysis was completed with SAS Studio, v3.8.
A total of 353 individuals had documented COVID-19 vaccine and antibody test dates (58% Pfizer, 38% Moderna, and 4% Johnson & Johnson). Of these 353 patients, 72% developed antibodies, with a mean antibody test interval of 53 days (median 46) post final vaccine dose. 100% of those on no DMT (n = 34), injectables (n = 20), teriflunomide (n = 10), natalizumab (n = 71), and 97.8% of those on fumarates (n = 46/47) had a positive antibody result. One patient on cladribine (n = 1) had a negative antibody result. Of those on sphingosine-1 phosphate (S1P) modulators, 72.4% (n = 21/29) had a positive antibody result. Of those on anti-CD20 therapies, 37.6% (n = 53/141) had a positive antibody result. Multivariate modeling of the total cohort showed anti-CD20 therapy was significantly associated with lower odds of positive antibody response (OR = 0.024, 95% CI 0.01;0.05, p < 0.0001). Among S1P modulators, increased duration of therapy, and not lymphopenia, may be associated with lower odds of positive antibody response. Multivariate modeling of anti-CD20 therapies showed therapy duration < 1 year (OR 8.14, 95% CI 2.896;22.898 p < .0001) and prior COVID-19 infection (OR = 3.95, 95% CI 1.137;13.726, p = .03) were significantly associated with higher odds of a positive antibody response. In patients with recent B-cell data, mean B-cell count was higher in antibody-positive individuals compared to antibody-negative (32.9 vs. 3.9 cells, p = .0056).
MS DMTs had variable impact on antibody response with mRNA and viral vector COVID-19 vaccines. All patients on no DMT, interferons, glatiramer acetate, teriflunomide, natalizumab, and nearly all on fumarates had positive antibody responses post-vaccine. S1P modulators and anti-CD20 therapies attenuated antibody response post-vaccine. For patients on anti-CD20 therapies, shorter duration of therapy and prior COVID-19 infection predicted positive antibody response. Further studies are needed to determine clinical significance of antibody testing, development of cellular mediated immunity, and benefits of booster vaccinations.
先前的研究表明，在免疫抑制人群中，COVID-19 疫苗的体液反应降低。多发性硬化症（MS）的疾病修正疗法（DMT）具有不同的免疫调节作用，并且所有 DMT 的可用数据有限。我们旨在确定 DMT 对 MS 患者 COVID-19 疫苗接种后抗体反应的影响。
在 2021 年 3 月至 8 月期间，确定了有记录的 COVID-19 疫苗接种日期和接种后抗刺突抗体结果的患者。从病历回顾中回顾性提取临床数据。对去识别数据进行分析以评估抗体反应，并使用多变量逻辑回归分析来确定抗体反应的临床和人口统计学预测因素。使用 SAS Studio，v3.8 完成数据分析。
共有 353 名患者有记录的 COVID-19 疫苗和抗体检测日期（58%为辉瑞，38%为 Moderna，4%为强生）。在这 353 名患者中，72%产生了抗体，最后一剂疫苗后平均抗体检测间隔为 53 天（中位数 46）。使用无 DMT（n=34）、注射剂（n=20）、特立氟胺（n=10）、那他珠单抗（n=71）和 97.8%的富马酸酯（n=46/47）的患者均有阳性抗体结果。1 名使用克拉屈滨（n=1）的患者抗体检测结果为阴性。在使用鞘氨醇-1 磷酸（S1P）调节剂的患者中，72.4%（n=21/29）的抗体检测结果为阳性。在使用抗 CD20 治疗的患者中，37.6%（n=53/141）的抗体检测结果为阳性。对总队列进行多变量建模显示，抗 CD20 治疗与较低的抗体阳性反应几率显著相关（OR=0.024，95%CI 0.01；0.05，p<0.0001）。在 S1P 调节剂中，治疗持续时间的增加，而不是淋巴细胞减少，可能与较低的抗体阳性反应几率相关。对抗 CD20 治疗进行多变量建模显示，治疗持续时间<1 年（OR 8.14，95%CI 2.896；22.898 p<0.0001）和既往 COVID-19 感染（OR=3.95，95%CI 1.137；13.726，p=0.03）与较高的抗体阳性反应几率显著相关。在最近有 B 细胞数据的患者中，抗体阳性患者的 B 细胞计数明显高于抗体阴性患者（32.9 与 3.9 细胞，p=0.0056）。
MS DMT 对 mRNA 和病毒载体 COVID-19 疫苗的抗体反应有不同的影响。所有使用无 DMT、干扰素、格拉替雷胺、特立氟胺、那他珠单抗和几乎所有使用富马酸酯的患者在接种疫苗后均产生了阳性抗体反应。S1P 调节剂和抗 CD20 治疗会减弱疫苗接种后的抗体反应。对于使用抗 CD20 治疗的患者，治疗持续时间较短和既往 COVID-19 感染预测了抗体的阳性反应。需要进一步的研究来确定抗体检测的临床意义、细胞介导免疫的发展以及加强疫苗接种的益处。
