2021 CMSC Annual Meeting

Lowered COVID-19 mRNA Vaccine Antibody Response in MS Patients Treated with B -Cell Depleting and S1P-Receptor-Targeting Therapies Compared to Controls: An Interim Analysis

Background: There are two mRNA vaccines targeting the SARS-CoV2 virus widely used in the U.S. There is limited knowledge about SARS-CoV2 mRNA vaccine response in multiple sclerosis (MS) patients treated with high efficacy immunotherapies. Objectives: Our goal was to assess the SARS-CoV2 Spike antibody response in MS patients treated with sphingosine-1-phosphate receptor-targeting therapies, fingolimod and siponimod, as well as the B cell depleting immunotherapies, ofatumumab and ocrelizumab. Methods: Patients with a diagnosis of MS, aged 18-65 on four targeted immunotherapies (fingolimod, siponimod, ofatumumab, ocrelizumab) for at least 3 months prior to the first dose mRNA SARS-CoV2 vaccine (either Pfizer or Moderna) were offered enrollment into the study. A cohort of healthy controls who received the mRNA vaccines were also enrolled. Blood samples for the SARS-CoV2 Spike antibody (Anti-SARS-CoV2 S, Roche-Elecsys) were collected 2-3 months after the second mRNA vaccine. The proportion who seroconverted (antibody>0.4 U/ml) in MS and controls as well as SARS-CoV2 Spike comparative antibody levels were assessed. We present results of our interim analysis. Results: At this interim timepoint, a total of 40 MS patients (7 fingolimod and 33 ocrelizumab) and 31 controls were included in this analysis. Only one ofatumumab-treated patient was enrolled and was therefore not included in this analysis. No siponimod-treated patients were enrolled to date. 35% of MS patients (14/40) seroconverted, compared to 100% (31/31) in the control group, with an estimated risk difference of -0.65, (95% confidence interval: -0.80, -0.50; Fisher’s exact test, p=1.4*10-9). Seroconversion occurred in 100% (31/31) of the controls, 71.4% (5/7) of the fingolimod-treated patients and 27.3% (9/33) of the ocrelizumab-treated patients, (three group comparison, Fisher’s exact test p-value =2.1*10-10; comparison of fingolimod to ocrelizumab, Fisher’s exact test p-value=0.039). The Spike antibody median level in MS patients was <0.4 U/ml and the median level in healthy controls was 1663 U/ml, (Wilcoxon rank sum test, p-value=7.8*10-13). The median Spike antibody level in the ocrelizumab group was <0.4 U/ml and the median level in the fingolimod was 3.82 U/ml, (Wilcoxon test, p-value=0.022). Total IgG correlated with Spike antibody levels in the ocrelizumab-treated group only (Spearman correlation, p=0.025). Conclusions: Compared to healthy controls, MS patients on ocrelizumab have significantly lower rates of seroconversion in response to the mRNA SARS-CoV2 vaccines. Median SARS-CoV2 Spike antibody levels were significantly higher in fingolimod compared to ocrelizumab-treated patients; however, both were lower than healthy controls. This study is funded by Novartis Pharmaceuticals Corporation