Seroconversion following vaccination against SARS-CoV-2 in people with MS: Impact of disease modifying therapy

Introduction: People with multiple sclerosis (MS) have faced particular concerns around vaccine efficacy and timing with respect to disease modifying therapy (DMT). Clinical advice has varied around delaying or suspending DMT to optimise vaccine response. Aims: To provide an understanding of vaccine response across DMTs to inform risk-benefit discussions with people with MS, and guide therapy choice. Methods: People with MS were invited to provide dried blood spots for analysis. Where possible, samples were obtained prior to vaccination and at 6 weeks following each vaccination. Serum from 4mm punched dried blood spots was resuspended in triton- PBS, and antibodies against SARS-COV-2 spike receptor binding domain protein assayed using the GloBody technique. The assay was validated against Roche Elecsys. Results: 98 participants had samples available for analysis. No samples had detectable anti-spike RBD IgG detectable pre-vaccination (n=34). A significant increase in anti-spike RBD IgG titre was seen following second vaccination (v2;n=98) compared to first vaccination (v1;n=34) (p<0.001). 16% (8/50) of those on anti-CD20 monoclonal antibodies demonstrated an IgG response to v2;in a logistic regression model this was significantly different to natalizumab (73% seroconverted, n=11), oral cladribine (73% seroconverted, n=11) and dimethyl fumarate (89% seroconverted, n=9). Alemtuzumab (40% seroconverted;n=5) and fingolimod (0% seroconverted, n=3) were not significantly different, although limited by small numbers. IgG titre was significantly lower in people who had received ocrelizumab following second vaccination compared to other DMT (p<0.001). Total time on treatment had a borderline relationship with IgG titre following v2 in the anti- CD20 cohort in a linear regression model (p=0.06);no relationship was seen between time from infusion and IgG response. In a univariate model excluding DMT, vaccine type (p<0.001), gender (p=0.023), EDSS (p=0.042), and time between vaccination doses (p=0.03) influenced odds of seroconversion;in a multivariate model only gender (OR male 0.13, p=0.027) and vaccine type (OR Pfizer 15.2, p<0.001) contributed significantly. Conclusions: DMT, vaccine type and gender have differential impacts on IgG response to vaccination, both in terms of seroconversion and antibody titre. The impact of these factors on susceptibility to clinical infection and longer term protection remain to be determined.